As more states legalize cannabis, the push to "deschedule" it from the Controlled Substances Act is gaining momentum. At the same time, the Food and Drug Administration (FDA) recently approved the first conventional drug containing a cannabinoid derived from cannabis—cannabidiol (CBD) for two rare seizure disorders. This would all seem to bode well for proponents of full federal legalization of medical cannabis. But some traditional providers are wary of drug companies pulling medical cannabis into the regular small molecule drug development system. The FDA's focus on precise analytical characterization and on individual active and inactive ingredients may be fundamentally inconsistent with the "entourage effects" theory of medical cannabis. Traditional providers may believe that descheduling cannabis would free them to promote and distribute their products free of federal intervention, both locally and nationally. Other producers appear to assume that descheduling would facilitate a robust market in cannabis-based edibles and dietary supplements. In fact, neither of these things is true. If cannabis were descheduled, the FDA's complex and comprehensive regulatory framework governing foods, drugs, and dietary supplements would preclude much of this anticipated commerce. For example, any medical claims about cannabis would require the seller to complete the rigorous new drug approval process, the cost of which will be prohibitive for most current traditional providers. Likely also unexpected to some, there is no pathway forward for conventional foods containing cannabis constituents, with the (probably exclusive) exception of certain hemp seed ingredients, if those foods cross state lines. And it will certainly come as a shock to many that federal law already prohibits the sale of dietary supplements containing CBD--including those already on the market as well as those made from "hemp," which has recently been descheduled under the 2018 Farm Bill. This Article describes in detail the surprising reach of the FDA and then outlines three modest, but legal, pathways forward for cannabis-based products in a world where cannabis has been descheduled.

Canada federally legalised recreational cannabis use among adults in October 2018. The impact this will have on Canadian youth is cause for concern. The current study examined changes in youth cannabis use over the time prior to legalisation to explore the impact of the beginning federal discourse around legalisation during the 2016/2017 school year.COMPASS, a prospective cohort study based on annual self-administered questionnaires.Ontario and Alberta during the first 6 years of the COMPASS study (2012/2013 to 2017/2018).Canadian grade 9-12 students attending secondary schools participating in COMPASS. In total, 2 30 404 questionnaires were included in the analysis (Y1: 2012/2013, n=24 173; Y2: 2013/2014, n=45 298; Y3: 2014/2015, n=42 355, Y4: 2015/2016, n=40 436; Y5: 2016/2017, n=37 060; Y6: 2017/2018, n=34 897).Lifetime cannabis use, past-year cannabis use, weekly cannabis use, ease of access to cannabis and age at first cannabis use.Cannabis never-use decreased between Y5 and Y6. Changes in age at first cannabis use mirrored this trend, with male students consistently starting younger. Cannabis access rates increased from Y4, mainly led by female students. Lifetime and past-year use rates were lowest in Y4 then increased in Y5 and Y6 due to a rise in the occasional use more common among female students, who reported use increases first. Non-white students were more likely use cannabis, with black and Aboriginal students the only two groups consistently reporting more weekly than occasional use, though with opposing trajectories. Overall, Aboriginal students had the highest odds of reporting lifetime, past-year and weekly use among the demographic groups examined.After a steady decrease in patterns of cannabis among youth over several years, it appears that there has been a gradual increase in cannabis use among youth following the start of discourse around cannabis legalisation, with some populations of youth being at greater risk.

Psychiatric and addictologic complications of new synthetic products. New synthetic products (NSP) have completely changed the current scene of addictions. Also known as designer drugs, legal highs, herbal highs, bath salts, plant fertilizers, incense, research chemicals, they have made their emergence on the drug market in the late 1990s. Legal or herbal highs consist of uncontrolled psychoactive substances, obtained by chemical synthesis or derived from plants. Essentially produced in China and India, but also in Europe, their diffusion brings new communication technologies, fixes the offer and directs the users' demand on this specific market. They are mostly sold over the Internet and are generally a "legal" pseudo- alternative to controlled and regulated psychoactive products. They are consumed because of their effects mimicking those of an illicit substance such as cocaine, amphetamine, methamphetamine, cannabis, opioids for example. NSP induce numerous psychiatric, somatic, addictologic and social complications.

Cannabis use disorders and psychiatric comorbidities. Psychiatric disorders and personality disorders are common among patients with cannabis use disorders. Symptoms of cannabis intoxication or withdrawal need to be disentangled from symptoms of psychiatric disorders. Cannabis use disorders and psychiatric disorders worsen each other. Cannabis use disorders could induce psychiatric disorders, in particular depressive disorders and anxiety disorders. Cannabis withdrawal anxiety typically begins after cannabis use has been stopped or reduced. Patients with cannabis use disorder experience, on a daily basis, subthreshold withdrawal anxiety symptoms, characterized by irritability associated with craving for cannabis. By contrast, individuals with primary anxiety disorders have different features. Integrated approaches to treatment for patients presenting with co-occurring cannabis use disorders and psychiatric disorders are recommended, including simultaneous treatments.

To survey adolescents with type 1 diabetes mellitus (T1DM) about their knowledge and application of harm-reduction recommendations when they engage in alcohol and other illicit substance use.Cross-sectional survey and chart review of adolescents with T1DM aged 13 to 18 years.One hundred and ninety patients were approached and 164 were included in the analysis. Mean age was 15.6 years (standard deviation [SD]=1.5). Fifty-one per cent were male. Of those who reported consuming alcohol, 95% knew that they should have a friend or parent check their blood glucose in the middle of the night after drinking but only 62% reported actually doing this in practice. Similarly, 98% reported knowing that they should wear a medic alert identification but only 79% reported actually doing this. Of those who reported consuming cannabis, 14% reported forgetting to check blood glucose and 14% reported forgetting insulin when using cannabis. From the chart review, a significantly lower proportion of adolescents reported substance use during their clinic visits (alcohol 26%, tobacco 19%, illicit substance 25%) compared to the self report in the survey (alcohol 55%, tobacco 30%, illicit substance 32%).Adolescents' knowledge of harm-reduction practices for the use of alcohol and other illicit substances is not always put to practice. Motivating adolescents to use their knowledge in practice is an important area to improve in diabetes self-management. Those who reported engaging in substance use in the survey had not always reported use during interactions with health care providers. This emphasizes the need for unbiased, universal education of all adolescents in the clinic.

Physical and psychological symptom burden in patients with advanced chronic kidney disease (CKD) is significantly debilitating; yet, it is often inadequately treated. Legalization of cannabis in Canada may attract increasing interest from patients for its medical use in refractory symptom management, but its indications and long-term adverse health impacts are poorly established, creating a challenge for clinicians to support its use. In this review, we summarize key clinical studies and the level of evidence for nonsynthetic cannabinoids in the treatment of common symptoms encountered in advanced stages of CKD, including chronic pain, nausea and vomiting, anorexia, pruritus, and insomnia.Medline and Embase.A search was conducted in MEDLINE and EMBASE (inception to March 1, 2018) on cannabis and CKD symptoms of interest, complemented with a manual review of bibliographies. Studies that examined synthetic cannabinoids that are manufactured to mimic the effects of ∆9-tetrahydrocannabinol such as dronabinol, levonantradol, nabilone, and ajulemic acid were excluded. We focused on studies with higher level of evidence where available, and quality of studies was graded based on the Oxford Centre for Evidence-based Medicine Levels of Evidence (1a to 5).Based on studies conducted in patients without renal impairment, those treated with nonsynthetic cannabinoids were 43% to 300% more likely to report a ≥30% reduction in chronic neuropathic pain compared with placebo. However, there is currently insufficient evidence to recommend nonsynthetic cannabinoids for other medical indications, although preliminary investigation into topical endocannabinoids for uremia-induced pruritus in end-stage renal disease is promising. Finally, any benefits of cannabis may be offset by potential harms in the form of cognitive impairment, increased risk of mortality post-myocardial infarction, orthostatic hypotension, respiratory irritation, and malignancies (with smoked cannabis).Nonsynthetic cannabinoid preparations were highly variable between studies, sample sizes were small, and study durations were short. Due to an absence of studies conducted in CKD, recommendations were primarily extrapolated from the general population.Until further studies are conducted, the role of nonsynthetic cannabinoids for symptom management in patients with CKD should be limited to the treatment of chronic neuropathic pain. Clinicians need to be cognizant that nonsynthetic cannabinoid preparations, particularly smoked cannabis, can pose significant health risks and these must be cautiously weighed against the limited substantiated therapeutic benefits of cannabis in patients with CKD.

Cannabis is the most used illicit substance in the world. As many countries are moving towards decriminalization, it is crucial to determine whether and how cannabis use affects human brain and behavior. The role of the cerebellum in cognition, emotion, learning, and addiction is increasingly recognized. Because of its high density in CB1 receptors, it is expected to be highly affected by cannabis use. The aim of this systematic review is to investigate how cannabis use affects cerebellar structure and function, as well as cerebellar-dependent behavioral tasks. Three databases were searched for peer-reviewed literature published until March 2018. We included studies that focused on cannabis effects on cerebellar structure, function, or cerebellar-dependent behavioral tasks. A total of 348 unique records were screened, and 40 studies were included in the qualitative synthesis. The most consistent findings include (1) increases in cerebellar gray matter volume after chronic cannabis use, (2) alteration of cerebellar resting state activity after acute or chronic use, and (3) deficits in memory, decision making, and associative learning. Age of onset and higher exposure to cannabis use were frequently associated with increased cannabis-induced alterations. Chronic cannabis use is associated with alterations in cerebellar structure and function, as well as with deficits in behavioral paradigms that involve the cerebellum (eg, eyeblink conditioning, memory, and decision making). Future studies should consider tobacco as confounding factor and use standardized methods for assessing cannabis use. Paradigms exploring the functional activity of the cerebellum may prove useful as monitoring tools of cannabis-induced impairment.

Federal barriers and logistical challenges have hindered measurement of the real time effects from the types of cannabis products used medically by millions of patients in vivo. Between 06/06/2016 and 03/05/2018, 3,341 people completed 19,910 self- administrated cannabis sessions using the mobile device software, ReleafApp to record: type of cannabis product (dried whole natural Cannabis flower, concentrate, edible, tincture, topical), combustion method (joint, pipe, vaporization), Cannabis subspecies (C. indica and C. sativa), and major cannabinoid contents (tetrahydrocannabinol, THC; and cannabidiol, CBD), along with real-time ratings of health symptom severity levels, prior-to and immediately following administration, and reported side effects. A fixed effects panel regression approach was used to model the within-user effects of different product characteristics. Patients showed an average symptom improvement of 3.5 (SD = 2.6) on an 11-point scale across the 27 measured symptom categories. Dried flower was the most commonly used product and generally associated with greater symptom relief than other types of products. Across product characteristics, only higher THC levels were independently associated with greater symptom relief and prevalence of positive and negative side effects. In contrast, CBD potency levels were generally not associated with significant symptom changes or experienced side effects.

Will cannabis oil live up to its hype for epilepsy patients in Texas?

Synthetic cannabinoids are, typically, full agonists at the cannabinoid CB1 receptor, and therefore considerably more potent than natural cannabis and may have correspondingly more serious psychological effects. Despite government sanctions against their production they continue to be available in ever-increasing varieties over the Internet. The psychological consequences of synthetic cannabinoid use are relatively unknown.The purpose of this study was to synthesise the available research on the psychological consequences of synthetic cannabinoid use.A literature search of three databases was conducted in February 2018, including the following keywords: Spice, synthetic cannabis, cognition, affect, behaviour, psychosis, depression and anxiety.Seventeen studies involving a variety of participants were eligible for inclusion: one controlled administration study, seven cross-sectional studies, five Internet surveys and four qualitative studies. The controlled administration study showed that, compared to placebo, synthetic cannabinoids acutely affected some aspects of cognitive functioning and subjective psychological ratings. Non-controlled, cross-sectional studies generally showed that synthetic cannabinoid users had lower performance on cognitive tasks and showed elevated symptomatology (e.g. paranoia) compared to both natural cannabis and non-cannabis users. Methodological limitations were noted across different study designs. There is limited research on how doses, frequency or type of synthetic cannabinoid influence outcomes.Acute synthetic cannabinoid use can result in a range of psychological outcomes and, when non-intoxicated, synthetic cannabinoid users appear to differ from natural cannabis and non-users on various affective and cognitive domains. As synthetic cannabinoid use is increasing in at-risk populations there is an urgent need for more and better research to inform users, professionals and policymakers.

The relationship between cannabis and violence remains unclear, especially amid those with severe mental illnesses (SMI). The objective of this meta-analysis was to investigate the cannabis-violence association in a population of individuals with a SMI.A systematic search of literature using PubMed, PsychINFO, Web of Science and Google scholar was performed (any time-August 2018). All peer-reviewed publications assessing both cannabis use and the perpetration of violence in an SMI sample were included. Data on several key study characteristics such as the proportion of SMI in the sample as well as the number of cannabis users and violent participants were extracted. Odds ratios (OR) were likewise extracted and aggregated with random-effects models.Of the potential 2449 articles that were screened for eligibility, 12 studies were analyzed using a random-effect meta-analysis. Results showed a moderate association between cannabis use and violence (OR = 3.02, CI = 2.01-4.54, p = 0.0001). The association was significantly higher when comparing cannabis misuse (OR = 5.8, CI = 3.27-10.28, p = 0.0001) to cannabis use (OR = 2.04, CI = 1.36-3.05, p = 0.001).These findings are clinically relevant for violence prevention/management and highlight the necessity of further investigations with methodologically-sound studies. Thus, longitudinal studies adjusting for important confounding factors (i.e., psychopathic traits and stimulant use) are warranted.

The objective of this review was to identify and examine the pharmacokinetic and pharmacodynamic interactions between cannabidiol (CBD)-only products, such as CBD oil, and anticancer agents. A literature search of PubMed (1980 to September 2018) and the Cochrane Collection (1980 to September 2018) was performed using the following search terms: "cannabidiol," "cancer," "cannabis," "marijuana," and "interaction," as well as any combination of these terms. Literature was excluded if it did not appear in the search when limited to the "full text" filter on PubMed, if it was not published in the English language, or if it did not explore potential pharmacodynamic or pharmacokinetic interactions of CBD and anticancer agents. There were 10 studies that met these inclusion criteria. The majority of the facts regarding the interactions with CBD were found using in vitro studies and the true in vivo implications are not well-known. Minimal data were available regarding the interactions between CBD and anticancer agents. However, pharmacists should always consider the possibility of interactions and their consequences whenever they are aware of a patient using CBD products.

Disturbances in self-regulatory control are involved in the initiation and maintenance of addiction, including cannabis use disorder (CUD). In adults, chronic cannabis use is associated with disturbances in fronto-striatal circuits during tasks that require the engagement of self-regulatory control, including the resolution of cognitive conflict. Understudied are the behavioral and neural correlates of these processes earlier in the course of cannabis use, disentangled from effects of long-term use. The present study investigates the functioning of fronto-striatal circuits during the resolution of cognitive conflict in cannabis-using youth.Functional magnetic resonance imaging data was acquired from 28 cannabis-using (CU) youth and 32 age-matched healthy participants (HC) during the performance of a Simon task. General linear modeling was used to compare patterns of brain activation during correct responses to conflict stimuli across groups. Psychophysiological interaction analyses were used to examine conflict-related fronto-striatal connectivity across groups. Associations of fronto-striatal activation and connectivity with cannabis use measures were explored.Reduced conflict-related activity was detected in CU relative to HC youth in fronto-striatal regions, including ventromedial prefrontal cortex (vmPFC), striatum, pallidum and thalamus. Fronto-striatal connectivity did not differ across groups, but negative connectivity between vmPFC and striatum was detected in both groups.These findings are consistent with previous reports of cannabis-associated disturbances in fronto-striatal circuits in adults and point to the specific influence of cannabis on neurodevelopmental changes in youth. Future studies should examine whether fronto-striatal functioning is a reliable marker of CUD severity and potential target for circuit-based interventions.

Background Drugged driving, or driving under the influence of any drug, is a growing public health concern, especially with the recent legislation legalizing marijuana use in certain states in the USA. We sought to gain a better understanding of the surgeons' perspective regarding marijuana (MJ) and alcohol (ETOH) and the relationship of recent laws to identification of MJ and ETOH in trauma victims. Methods Members of a national trauma surgical organization were asked to participate in an Institutional Review Board (IRB)-approved, web-based survey which centered on attitudes, knowledge, and beliefs regarding ETOH and MJ as they related to injury. Two Level I trauma center registries (located in TX and CA) were queried for the incidence of motor vehicular collision (MVC) and the presence of ETOH (defined as > 0.08 g/dL) or MJ from 2006 thru 2012. Results A total of 127 trauma surgeons participated in the survey. The majority were male (84%, n = 107) and with a median age of 52. Most were in surgical practice for greater than 11 years (78%, n = 99) and worked at a Level I trauma center (78%, n = 99) in an academic institution (65%, n = 83). MJ was illegal in the states where most of the participants were in practice (79%, n = 100), but 90% (n = 114) of respondents from states where MJ is legal stated they have not seen an increase in MVC since MJ was legalized. At the TX trauma center, only 4% of patients involved in a vehicular trauma tested positive for MJ, 21% of patients had the presence of ETOH, and 3% had both. For both MJ and also ETOH, the incidence remained the same each year. In CA, there was little yearly variation in the incidence of patients that tested positive for MJ (23%), ETOH (50%), and both (7%). In addition, the incidence of MJ was essentially unchanged after the decriminalization law was passed in 2010. Conclusion The prevalence of cannabis and alcohol varies among the states studied, TX and CA. The impact of decriminalization of marijuana did not seem to affect the incidence of drugged driving with marijuana in CA.

Phobic anxiety disorders are among the most prevalent psychiatric disorders and are burdensome in terms of loss of quality of life and work productivity. Evidence-based treatments are relatively successful in the majority of patients, especially exposure therapy. However, a substantial subset of patients fails to achieve or stay in remission. Preclinical and genetic research have yielded evidence that the cannabinoid system is involved in the extinction of fear, presumed to underlie the beneficial effects of exposure therapy in phobic disorders. A cannabinoid constituent that may enhance endocannabinoid signaling is cannabidiol (CBD), a non-psychoactive component of cannabis. Hence, the addition of CBD to exposure therapy is expected to strengthen effects of treatment. To determine the added benefit of CBD on exposure therapy, we conduct a randomized controlled trial, in which patients in whom previous treatment as usual has not yielded sufficient response receive either CBD or placebo preceding 8 exposure sessions in a double-blind fashion. A subsidiary aim is to explore which (combination of) clinical, behavioral and genetic profiles of patients are related to treatment response.This is an 8-week multicenter, randomized, double-blind, placebo-controlled trial. Seventy-two patients with social phobia or panic disorder with agoraphobia with incomplete response to earlier treatment will be included from outpatient clinics in the Netherlands. Patients are randomized to augmentation of exposure therapy with 300 mg CBD or placebo. The study medication is administered orally, 2 h preceding each of the eight 90 min exposure sessions. Measurements will take place at baseline, first administration of medication, every session, mid-treatment, last administration of medication, post-treatment and at 3 and 6 months' follow-up. The primary outcome measure is the score on the Fear Questionnaire (FQ). In addition, determinants of the expected treatment enhancing effect of CBD will be explored.This is the first trial to investigate whether the addition of CBD to exposure therapy is effective in reducing phobic symptoms in treatment refractory patients with social phobia or panic disorder with agoraphobia.Netherlands Trial Register NTR5100 . Registered 13 March 2015. Protocol version: issue date 17 Jan 2018, protocol amendment number 7.

Psychotic experiences (PE) are dimensional phenomena in the general population that resemble psychotic symptoms, such as paranoia and hallucinations. This is the first twin study to explore the degree to which tobacco use and PE share genetic or environmental influences. Previous studies on the association between adolescent tobacco use and PE have not considered PE dimensionally, included negative symptoms, or accounted for confounding by sleep disturbance and stressful life events.An unselected adolescent twin sample (N = 3,787 pairs; mean age = 16.16 years) reported on PE (paranoia, hallucinations, cognitive disorganization, grandiosity, and anhedonia) and regularity of tobacco use. Parents rated the twins' negative symptoms. Regression analyses were conducted while adjusted for sociodemographic characteristics, prenatal maternal smoking, cannabis use, sleep disturbance, and stressful life events. Bivariate twin modeling was used to estimate the degree of genetic and common and unique environmental influences shared between tobacco use and PE.Regular smokers were significantly more likely to experience paranoia, hallucinations, cognitive disorganization, and negative symptoms (β = 0.17-0.34), but not grandiosity or anhedonia, than nonsmokers, after adjustment for confounders. Paranoia, hallucinations, and cognitive disorganization correlated ≥0.15 with tobacco use (r = 0.15-0.21, all p < .001). Significant genetic correlations (rA=0.37-0.45) were found. Genetic influences accounted for most of the association between tobacco use and paranoia (84%) and cognitive disorganization (81%). Familial influences accounted for 80% of the association between tobacco use and hallucinations.Tobacco use and PE during adolescence were associated after adjustment for confounders. They appear to co-occur largely because of shared genetic influences.

Trauma, particularly when experienced early in life, can alter neurophysiologic and behavioral development, thereby increasing risk for substance use disorders and related psychopathology. However, few studies have empirically examined trauma using well-characterized developmental samples that are followed longitudinally.The association of assaultive, non-assaultive, and sexual assaultive experiences before 10 years of age with developmental trajectories of brain function during response inhibition was examined by measuring electrophysiologic theta and delta oscillations during no-go and go conditions in an equal probability go/no-go task. Data were drawn from the Collaborative Study of the Genetics of Alcoholism (COGA) prospective cohort, composed of offspring who were aged 12 through 22 years at enrollment from high-risk and comparison families, with follow-ups at 2-year intervals since 2004. In addition, other important predictors of neurophysiologic functioning (eg, substance use, impulsivity, and parental alcohol use disorders) were investigated. Moreover, associations of neurophysiologic functioning with alcohol and cannabis use disorder symptom counts and externalizing and internalizing psychopathology were examined.Individuals exposed to sexual assaultive trauma before 10 years of age had slower rates of change in developmental trajectories of no-go frontal theta during response inhibition. Importantly, effects remained significant after accounting for exposure to other traumatic exposures, such as parental history of alcohol use disorder and participants' substance use, but not measures of impulsivity. Further, slower rates of change in no-go frontal theta adolescent and young adult development were associated with increased risk for alcohol use disorder symptoms and internalizing psychopathology, but not for cannabis use disorder symptoms or externalizing psychopathology.Childhood sexual assault is associated with atypical frontal neurophysiologic development during response inhibition. This could reflect alterations in frontal lobe development, synaptic pruning, and/or cortical maturation involving neural circuits for inhibitory control. These same areas could be associated with increased risk for young adult alcohol use disorder symptoms and internalizing psychopathology. These findings support the hypothesis that changes in neurocognitive development related to early sexual trauma exposure could increase the risk for mental health and substance use problems in young adulthood.

The advances in Mobile Health (M-health) technologies has led to an increase in the numbers of alcohol and drugs applications on the commercial stores. Content analyses and reviews of applications to date have demonstrated that most of these applications are for entertainment or information purposes. More recent content analyses have identified common behavioural change techniques in substance applications. Nevertheless, there remain several limitations of existing content analyses and reviews of applications. There is an increasing prevalence of other substance-related disorders, such as that of stimulants and opioids, but the existing content analyses are limited to an analysis of alcohol and cannabis applications. Only two of the content analyses performed to date have attempted to identify applications that have their basis on a theoretical approach, based on the identification of behavioural change techniques or motivational techniques. There is a need to identify applications on the commercial stores that replicate conventional psychological interventions, or at least provide elements of conventional psychological interventions using behavioural change techniques that are integrated into the application. Further evaluative research could be done on these applications to determine if they are efficacious before using them for patient care. To address the limitation that existing content analyses have only focused on reviews of alcohol and cannabis applications, we propose for there to be updated content analyses for alcohol and cannabis, and new content analyses for other substances of abuse (such as opioids and stimulants). We like to suggest that future reviews consider keywords such as abstinence or recovery, and ones that relate to psychological therapies, such as self-determination or attention bias retraining, as commercial applications that have an underlying psychological basis might be categorised differently, under different keyword terms. We have evidence of how a better search strategy identifies previously unrecognised applications for attentional bias modification.

Almost 50,000 children and young people are affected by life-limiting conditions in the United Kingdom, around a third of which use children's hospices. Anecdotal evidence suggests that cannabinoid-based medicines (CBMs), specifically cannabis oil (CO), are being used by families with increasing frequency to manage distressing symptoms. The use of most nonprescription CBMs in the United Kingdom remains illegal.The objective of the study was to identify the prevalence of CO use by families who use children's hospices in the United Kingdom, and the approaches taken by those services to manage it.An electronic survey was sent to each of the 54 children's hospices in the United Kingdom between May and July 2018, comprising 10 questions.Forty children's hospices from across the four countries of the United Kingdom responded to the survey, representing 74% of British children's hospices. About 87.5% of hospices knew of children who use CO therapeutically. Sixty-nine percent of those hospices have received requests to administer CO during an episode of care. Approaches by organizations around CO management varied across the sectors, including arrangements for storage, administration, and recording of its use. Hospices highlighted how the lack of available guidance made decision making more challenging. Only a third of responding organizations routinely questioned families about the use of cannabis when prescribing medicines.CO is used extensively by children who use children's hospices. Despite recognizing the use of CO, many hospices are unable to support it. There is a need for clear guidelines on how hospices should approach the care needs of children, allowing hospices to meet the needs of children who use CO, and families in a safe, consistent, and relevant way, safeguarding all children, families, and professionals within the organization.

We describe two patients with a confirmed diagnosis of high-grade gliomas (grades III/IV), both presenting with O6-methylguanine-DNA methyltransferase (MGMT) methylated and isocitrate dehydrogenase (IDH-1) mutated who, after subtotal resection, were submitted to chemoradiation and followed by PCV, a multiple drug regimen (procarbazine, lomustine, and vincristine) associated with cannabidiol (CBD). Both patients presented with satisfactory clinical and imaging responses at periodic evaluations. Immediately after chemoradiation therapy, one of the patients presented with an exacerbated and precocious pseudoprogression (PSD) assessed by magnetic resonance imaging (MRI), which was resolved in a short period. The other patient presented with a marked remission of altered areas compared with the post-operative scans as assessed by MRI. Such aspects are not commonly observed in patients only treated with conventional modalities. This observation might highlight the potential effect of CBD to increase PSD or improve chemoradiation responses that impact survival. Further investigation with more patients and critical molecular analyses should be performed.

As the legalization of medical cannabis continues across the USA, oncology care providers will be increasingly asked to provide recommendations regarding its use in the cancer setting. In this article, we review recent literature that analyzes cannabis use specifically in patients with cancer and provide an accessible guide for clinicians, researchers, and patients.We aimed to answer questions about the availability of cannabis in the USA, the trials supporting its use in the cancer setting, and the important factors to consider related to safety. Thirty states plus the District of Columbia have established comprehensive medical cannabis programs, each with different regulations and products available. In June 2018, Epidiolex, a cannabis extraction product containing 99% CBD, was approved to treat refractory seizures; however, whole-plant products and non-prescription extraction products dominate the market. Recent randomized, placebo-controlled studies of nabiximols (Sativex) in patients with refractory cancer-pain have largely shown no significant benefits. Conversely, large observational studies suggest patients with cancer using cannabis report significant improvement of many common symptoms. Cannabis use appears well tolerated, with few serious adverse effects reported. Though prospective clinical trials are needed to provide the robust data required to establish the proper role of cannabinoid and cannabis-based therapy in cancer patients, physicians can draw upon the knowledge currently available to have informed discussions with their patients.

We conducted a review of systematic reviews (SRs) and randomized-controlled trials (RCTs) to analyze efficacy and safety of cannabis-based medication in patients with mental disorders. Five data bases were systematically searched (2006-August 2018); 4 SRs (of 11 RCTs) and 14 RCTs (1629 participants) were included. Diagnoses were: dementia, cannabis and opioid dependence, psychoses/schizophrenia, general social anxiety, posttraumatic stress disorder, anorexia nervosa, attention-deficit hyperactivity disorder, and Tourette`s disorder. Outcome variables were too heterogeneous to conduct a  meta-analysis. A narrative synthesis method was applied. The study quality was assessed using the risk-of-bias tool and SIGN-checklists. THC- and CBD-based medicines, given as adjunct to pharmaco- and psychotherapy, were associated with improvements of several symptoms of mental disorders, but not with remission. Side effects occurred, but severe adverse effects were mentioned in single cases only. In order to provide reliable treatment recommendations, more and larger RCTs with follow-up assessments, consistent outcome measures and active comparisons are needed.

Mortality associated with cannabis used for treatment of epilepsy is not well documented. We discuss two fatalities in the setting of epilepsy and self-determined therapy with cannabis (SDTC). One patient had probable sudden unexpected death in epilepsy, the second death was due to seizure-associated drowning. Both directed SDTC over conventional anti-seizure medications. Where recreational cannabis is legal, decisions to use cannabis are often self-directed and independent of physician advice of cannabis risks, in part because physicians may not be aware of the risk of SDTC. Further study of morbidity and mortality of SDTC in patients with epilepsy is needed.

Introduction: Magistral preparations of therapeutic cannabis are extracted from standardized products imported from Holland or from the Florence Military Pharmaceutical Chemical Works, but extraction protocols differ among galenic laboratories. This study assessed the inter-laboratory variability in concentrations of cannabidiol (CBD), cannabinol (CBN), tetrahydrocannabinol (THC), and tetrahydrocannabinolic acid (THCA) among different magistral oil preparations. Methods: 219 samples of Bediol, Bedrobinol, Bedrolite or FM-2 70 or 100 mg/ml in oil were collected from 3 laboratories. Concentrations of CBD, CBN, THC, and THCA were quantified by high-pressure liquid chromatography; inter-laboratories variability was assessed using the Kruskal-Wallis test. Results: A significant variability in CBD and THC concentrations was found for Bediol 70 mg/ml samples from 2 laboratories [for CBD: median 5.4 (range 4.8-6.6) vs. 6.1 (4.9-7.2) mg/ml, p = 0.033; for THC: 3.6 (3.1-3.9) vs. 4.0 (2.6-5.1) mg/ml, p = 0.020]. As for Bediol 100 mg/ml, a significant variability emerged in THC concentrations among the three considered laboratories [5.7 (-) vs. 4.2 (1.5-4.8) vs. 5.2 (4.2-6.9), p = 0.030]. No significant inter-laboratory variability emerged for Bedrocan and Bedrolite. Concentrations of CBD, CBN, and THC were

Transient receptor potential (TRP) channels are a group of membrane proteins involved in the transduction of a plethora of chemical and physical stimuli. These channels modulate ion entry, mediating a variety of neural signaling processes implicated in the sensation of temperature, pressure, and pH, as well as smell, taste, vision, and pain perception. Many diseases involve TRP channel dysfunction, including neuropathic pain, inflammation, and respiratory disorders. In the pursuit of new treatments for these disorders, it was discovered that cannabinoids can modulate a certain subset of TRP channels. The TRP vanilloid (TRPV), TRP ankyrin (TRPA), and TRP melastatin (TRPM) subfamilies were all found to contain channels that can be modulated by several endogenous, phytogenic, and synthetic cannabinoids. To date, six TRP channels from the three subfamilies mentioned above have been reported to mediate cannabinoid activity: TRPV1, TRPV2, TRPV3, TRPV4, TRPA1, and TRPM8. The increasing data regarding cannabinoid interactions with these receptors has prompted some researchers to consider these TRP channels to be "ionotropic cannabinoid receptors." Although CB1 and CB2 are considered to be the canonical cannabinoid receptors, there is significant overlap between cannabinoids and ligands of TRP receptors. The first endogenous agonist of TRPV1 to be discovered was the endocannabinoid, anandamide (AEA). Similarly, N-arachidonyl dopamine (NADA) and AEA were the first endogenous TRPM8 antagonists discovered. Additionally, Δ9-tetrahydrocannabinol (Δ9-THC), the most abundant psychotropic compound in cannabis, acts most potently at TRPV2, moderately modulates TRPV3, TRPV4, TRPA1, and TRPM8, though Δ9-THC is not reported to modulate TRPV1. Moreover, TRP receptors may modulate effects of synthetic cannabinoids used in research. One common research tool is WIN55,212-2, a CB1 agonist that also exerts analgesic effects by desensitizing TRPA1 and TRPV1. In this review article, we aim to provide an overview and classification of the cannabinoid ligands that have been reported to modulate TRP channels and their therapeutic potential.

Malignant melanoma is a complex malignancy with significant morbidity and mortality. The incidence continues to rise, and despite advances in treatment, the prognosis is poor. Thus, it is necessary to develop novel strategies to treat this aggressive cancer. Synthetic cannabinoids have been implicated in inhibiting cancer cell proliferation, reducing tumor growth, and reducing metastasis. We developed a unique study focusing on the effects of treatment with a cannabinoid derivative on malignant melanoma tumors in a murine model.Murine B16F10 melanoma tumors were established subcutaneously in C57BL/6 mice. Mice were then treated with intraperitoneal injections of vehicle twice per week (control-group 1, n = 6), Cisplatin 5 mg/kg/wk (group 2; n = 6), and Cannabidiol (CBD) 5 mg/kg twice per week (group 3; n = 6). Tumors were measured and volume calculated as (4π/3) × (width/2)2 × (length/2). Tumor size and survival curves were measured. Results were compared using a one-way ANOVA with multiple comparison test.A significant decrease in tumor size was detected in mice treated with CBD when compared with the control group (P = 0.01). The survival curve of melanoma tumors treated with CBD increased when compared with the control group and was statistically significant (P = 0.04). The growth curve and survival curve of melanoma tumors treated with Cisplatin were significantly decreased and increased, respectively, when compared with the control and CBD-treated groups. Mice treated with Cisplatin demonstrated the longest survival time, but the quality of life and movement of CBD-treated mice were observed to be better.We demonstrate a potential beneficial therapeutic effect of cannabinoids, which could influence the course of melanoma in a murine model. Increased survival and less tumorgenicity are novel findings that should guide research to better understand the mechanisms by which cannabinoids could be utilized as adjunctive treatment of cancer, specifically melanoma. Further studies are necessary to evaluate this potentially new and novel treatment of malignant melanoma.

Chronic pain affects a significant proportion of the population and presents a major challenge to clinicians and pain specialists. Despite the availability of pharmacologic treatment options such as opioids, many patients continue to experience persistent pain. Cannabinoids present an alternative option with some data on efficacy; however, to date, a systematic review of adverse events (AEs) assessment and reporting in randomized clinical trials (RCTs) involving cannabinoids has not been performed. As a result, it is unclear whether a clear profile of cannabinoid-associated AEs has been accurately detailed in the literature. As cannabinoids are likely to become readily available for patients in the near future, it is important to study how well AEs have been reported in trials so that the safety profile of cannabinoids can be better understood.With a potentially enormous shift toward cannabinoid use for managing chronic pain and spasticity, this study aims to reveal the adequacy of AE reporting and cannabinoid-specific AEs in this setting. Spasticity is a major contributor to chronic pain in patients with multiple sclerosis (MS), with a comorbidity of 75%. Many cannabinoid studies have been performed in MS-related painful spasticity with relevant pain outcomes, and these studies will be included in this review for comprehensiveness. The primary outcome will be the quality of AE assessment and reporting by adherence to the Consolidated Standards of Reporting Trials (CONSORT) guidelines. Secondary outcomes will include the type of AE, method of AE reporting, severity of AE, frequency of AEs, patient withdrawals, and reasons for withdrawals.We will perform a systematic review by searching for primary reports of double-blind, randomized controlled trials of cannabinoids compared with placebo and any active comparator treatments for chronic pain, with a primary outcome directly related to pain (eg, pain intensity, pain relief, and pain-related interference). We will search the following databases: MEDLINE, Embase, Cochrane Library, and PsycINFO. RevMan software will be used for meta-analysis.The protocol has been registered on the International Prospective Register of Systematic Reviews (CRD42018100401). The project was funded in 2018 and screening has been completed. Data extraction is under way and the first results are expected to be submitted for publication in January or February 2019.This review will better elucidate the safety of cannabinoids for the treatment of chronic pain and spasticity through identifying gaps in the literature for AE reporting. Like in any new therapy, it is essential that accurate information surrounding the safety and efficacy of cannabinoids be clearly outlined and identified to balance the benefit and harm described for patients.PROSPERO CRD42018100401; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=100401.DERR1-10.2196/11637.

Globally, cannabis use is prevalent and widespread. There are currently no pharmacotherapies approved for treatment of cannabis use disorders.This is an update of a Cochrane Review first published in the Cochrane Library in Issue 12, 2014.To assess the effectiveness and safety of pharmacotherapies as compared with each other, placebo or no pharmacotherapy (supportive care) for reducing symptoms of cannabis withdrawal and promoting cessation or reduction of cannabis use.We updated our searches of the following databases to March 2018: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO and Web of Science.Randomised controlled trials (RCTs) and quasi-RCTs involving the use of medications to treat cannabis withdrawal or to promote cessation or reduction of cannabis use, or both, in comparison with other medications, placebo or no medication (supportive care) in people diagnosed as cannabis dependent or who were likely to be dependent.We used standard methodological procedures expected by Cochrane.We included 21 RCTs involving 1755 participants: 18 studies recruited adults (mean age 22 to 41 years); three studies targeted young people (mean age 20 years). Most (75%) participants were male. The studies were at low risk of performance, detection and selective outcome reporting bias. One study was at risk of selection bias, and three studies were at risk of attrition bias.All studies involved comparison of active medication and placebo. The medications were diverse, as were the outcomes reported, which limited the extent of analysis.Abstinence at end of treatment was no more likely with Δ9-tetrahydrocannabinol (THC) preparations than with placebo (risk ratio (RR) 0.98, 95% confidence interval (CI) 0.64 to 1.52; 305 participants; 3 studies; moderate-quality evidence). For selective serotonin reuptake inhibitor (SSRI) antidepressants, mixed action antidepressants, anticonvulsants and mood stabilisers, buspirone and N-acetylcysteine, there was no difference in the likelihood of abstinence at end of treatment compared to placebo (low- to very low-quality evidence).There was qualitative evidence of reduced intensity of withdrawal symptoms with THC preparations compared to placebo. For other pharmacotherapies, this outcome was either not examined, or no significant differences was reported.Adverse effects were no more likely with THC preparations (RR 1.02, 95% CI 0.89 to 1.17; 318 participants; 3 studies) or N-acetylcysteine (RR 0.94, 95% CI 0.71 to 1.23; 418 participants; 2 studies) compared to placebo (moderate-quality evidence). For SSRI antidepressants, mixed action antidepressants, buspirone and N-acetylcysteine, there was no difference in adverse effects compared to placebo (low- to very low-quality evidence).There was no difference in the likelihood of withdrawal from treatment due to adverse effects with THC preparations, SSRIs antidepressants, mixed action antidepressants, anticonvulsants and mood stabilisers, buspirone and N-acetylcysteine compared to placebo (low- to very low-quality evidence).There was no difference in the likelihood of treatment completion with THC preparations, SSRI antidepressants, mixed action antidepressants and buspirone compared to placebo (low- to very low-quality evidence) or with N-acetylcysteine compared to placebo (RR 1.06, 95% CI 0.93 to 1.21; 418 participants; 2 studies; moderate-quality evidence). Anticonvulsants and mood stabilisers appeared to reduce the likelihood of treatment completion (RR 0.66, 95% CI 0.47 to 0.92; 141 participants; 3 studies; low-quality evidence).Available evidence on gabapentin (anticonvulsant), oxytocin (neuropeptide) and atomoxetine was insufficient for estimates of effectiveness.There is incomplete evidence for all of the pharmacotherapies investigated, and for many outcomes the quality of the evidence was low or very low. Findings indicate that SSRI antidepressants, mixed action antidepressants, bupropion, buspirone and atomoxetine are probably of little value in the treatment of cannabis dependence. Given the limited evidence of efficacy, THC preparations should be considered still experimental, with some positive effects on withdrawal symptoms and craving. The evidence base for the anticonvulsant gabapentin, oxytocin, and N-acetylcysteine is weak, but these medications are also worth further investigation.

Due to the myriad of laws concerning cannabis, there is little empirical research regarding the veterinary use of cannabidiol (CBD). This study used the Veterinary Information Network (VIN) to gauge US veterinarians' knowledge level, views and experiences related to the use of cannabinoids in the medical treatment of dogs. Participants (n = 2130) completed an anonymous, online survey. Results were analyzed based on legal status of recreational marijuana in the participants' state of practice, and year of graduation from veterinary school. Participants felt comfortable in their knowledge of the differences between Δ9-tetrahydrocannabinol (THC) and marijuana, as well as the toxic effects of marijuana in dogs. Most veterinarians (61.5%) felt comfortable discussing the use of CBD with their colleagues, but only 45.5% felt comfortable discussing this topic with clients. No differences were found based on state of practice, but recent graduates were less comfortable discussing the topic. Veterinarians and clients in states with legalized recreational marijuana were more likely to talk about the use of CBD products to treat canine ailments than those in other states. Overall, CBD was most frequently discussed as a potential treatment for pain management, anxiety and seizures. Veterinarians practicing in states with legalized recreational marijuana were more likely to advise their clients and recommend the use of CBD, while there was no difference in the likelihood of prescribing CBD products. Recent veterinary graduates were less likely to recommend or prescribe CBD. The most commonly used CBD formulations were oil/extract and edibles. These were most helpful in providing analgesia for chronic and acute pain, relieving anxiety and decreasing seizure frequency/severity. The most commonly reported side-effect was sedation. Participants felt their state veterinary associations and veterinary boards did not provide sufficient guidance for them to practice within applicable laws. Recent graduates and those practicing in states with legalized recreational marijuana were more likely to agree that research regarding the use of CBD in dogs is needed. These same groups also felt that marijuana and CBD should not remain classified as Schedule I drugs. Most participants agreed that both marijuana and CBD products offer benefits for humans and expressed support for use of CBD products for animals.

The topic of Cannabis curries controversy in every sphere of influence, whether politics, pharmacology, applied therapeutics or even botanical taxonomy. Debate as to the speciation of Cannabis, or a lack thereof, has swirled for more than 250 years. Because all Cannabis types are eminently capable of cross-breeding to produce fertile progeny, it is unlikely that any clear winner will emerge between the "lumpers" vs. "splitters" in this taxonomical debate. This is compounded by the profusion of Cannabis varieties available through the black market and even the developing legal market. While labeled "strains" in common parlance, this term is acceptable with respect to bacteria and viruses, but not among Plantae. Given that such factors as plant height and leaflet width do not distinguish one Cannabis plant from another and similar difficulties in defining terms in Cannabis, the only reasonable solution is to characterize them by their biochemical/pharmacological characteristics. Thus, it is best to refer to Cannabis types as chemical varieties, or "chemovars." The current wave of excitement in Cannabis commerce has translated into a flurry of research on alternative sources, particularly yeasts, and complex systems for laboratory production have emerged, but these presuppose that single compounds are a desirable goal. Rather, the case for Cannabis synergy via the "entourage effect" is currently sufficiently strong as to suggest that one molecule is unlikely to match the therapeutic and even industrial potential of Cannabis itself as a phytochemical factory. The astounding plasticity of the Cannabis genome additionally obviates the need for genetic modification techniques.

[This corrects the article DOI: 10.3389/fneur.2018.00759.].

The objective of this study was to study the association between self-reported road traffic crashes (RTCs) and recent use of alcohol and medicinal and illicit drug use and self-reported speeding in the previous 2 years.During the period from April 2016 to April 2017, drivers of cars, vans, motorcycles, and mopeds were stopped in a Norwegian roadside survey performed in collaboration with the police. Participation was voluntary and anonymous. The drivers were asked to deliver an oral fluid sample (mixed saliva), which was analyzed for alcohol and 39 illicit and medicinal drugs and metabolites. In addition, data on age, sex, and self-reported speeding tickets and RTCs during the previous 2 years were collected.A total of 5,031 participants were included in the study, and 4.9% tested positive for the use of one or more illicit or medicinal drugs or alcohol. We found a significant, positive association between the use of cannabis and RTC involvement (odds ratio [OR] = 1.93; 95% confidence interval [CI], 1.05-3.57; P = 0.035) and also between previous speeding tickets and RTC involvement (OR = 1.39; 95% CI, 1.08-1.80; P = 0.012). In addition, older age groups were found to have a significant, negative association with RTC involvement, with ORs equal to or less than 0.49, when using the age group 16-24 as reference.Speeding, as an indicator of risk behavior, and the use of cannabis were associated with previous RTC involvement, whereas increasing age was significantly associated with lower risk. This is consistent with previous studies on RTCs.

To synthetize the data on the prevalence of major depressive disorders (MDD) in France in general population and in specific populations.A systematic review following the PRISMA criteria has been carried out. MEDLINE, google scholar, Isi web of science, PsychInfo et Cochrane library have been explored, from 2000 to April 2018.The prevalence of major depression in France over the last 12 months was around 8% in the 2000s and seems to have increased to 10% in the 2010s. Studies on national databases tend to underestimate this prevalence (<2%), retaining only the most severe depressions, hospitalized and treated with antidepressants. In specific populations, data has been published in HIV, epilepsy, some cancers and cardiovascular disease, cannabis and tobacco smokers.The prevalence of depression seems to have increased between the years 2000 and 2010 in France. Further studies should be published, especially in alcohol use disorder, cancers, cardiovascular diseases and immuno-inflammatory illnesses, due to their high prevalence and their specific relationships with MDD. Another study in the general French population should also be carried out. This data should help developing precision medicine to improve the care of MDD in France.

Introduction: Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide, and new therapeutic strategies are still required. Here we screened a synthetic cannabinoid library to identify compounds that uniformly reduce the viability of seven CRC cell lines. Material and Methods: Seven distinct CRC cell lines were treated with 10 μM cannabinoid compounds (from a library of 370 molecules) for 48 h, and cell viability was subsequently measured with MTS assay. Dose-response curves were conducted for compounds that were found to reproducibly reduce cell viability of one or more cell lines. Results: We identified 10 compounds from the library that were able to reduce cell viability of CRC cell lines (with an IC50 ≤ 30 μM). Of these compounds, seven were specific for CRC cells, and six were effective in all CRC cell lines tested. Treatment with traditional phytocannabinoids (THC or CBD) was either ineffective or much less potent and only partially efficacious. Treatment with antagonists for the known cannabinoid receptors (alone or in combination) failed to block the activity of the most potent of identified compounds. Conclusion: We identified three families of cannabinoid compounds that reduce CRC cell viability through a noncanonical receptor mechanism. Future modification of these compounds may lead to the development of novel therapies to treat this disease.

Introduction: Obesity is treatment-resistant, and is linked with a number of serious, chronic diseases. Adult obesity rates in the United States have tripled since the early 1960s. Recent reviews show that an increased ratio of omega-6 to omega-3 fatty acids contributes to obesity rates by increasing levels of the endocannabinoid signals AEA and 2-AG, overstimulating CB1R and leading to increased caloric intake, reduced metabolic rates, and weight gain. Cannabis, or THC, also stimulates CB1R and increases caloric intake during acute exposures. Goals: To establish the relationship between Cannabis use and body mass index, and to provide a theoretical explanation for this relationship. Results: The present meta-analysis reveals significantly reduced body mass index and rates of obesity in Cannabis users, in conjunction with increased caloric intake. Theoretical explanation: We provide for the first time a causative explanation for this paradox, in which rapid and long-lasting downregulation of CB1R following acute Cannabis consumption reduces energy storage and increases metabolic rates, thus reversing the impact on body mass index of elevated dietary omega-6/omega-3 ratios.

Since the late 1990s public opinion about cannabis legalization has become drastically more liberal, and some states have begun to legalize cannabis for recreational use. Why have attitudes changed so much? Prior research has considered a few of the reasons for this change, but this is the first comprehensive and empirically-based study to consider the wide range of potential causes for how and why this happened. We use data from the General Social Survey, National Study of Drug Use and Health, and word searches from the New York Times. We find that attitudes largely liberalized via intracohort changes. Most Americans developed more liberal views, regardless of their race and ethnicity, gender, education, religious or political affiliation, or religious engagement. Changes in cannabis use have had minimal effects on attitudes, and legalization of cannabis has not prompted attitude change in neighboring states. As to root causes, evidence suggests that a decrease in religious affiliation, a decline in punitiveness, and a shift in media framing all contributed to changing attitudes.

Healthcare providers play a critical role in facilitating patient access to medical cannabis. However, previous surveys suggest only a minority of providers believe that medical cannabis confers benefits to patients. Significant new knowledge about the potential benefits and harms of medical cannabis has recently emerged. Understanding current attitudes and beliefs of providers may provide insight into the ongoing challenges they face as states expand access to medical cannabis.We conducted an electronic survey of primary care providers in a large Minnesota-based healthcare system between January 23 and February 5, 2018. We obtained information about provider characteristics, attitudes and beliefs about medical cannabis, provider comfort level in answering patient questions about medical cannabis, and whether providers were interested in receiving additional education.Sixty-two providers completed the survey (response rate 31%; 62/199). Seventy-six percent of respondents were physicians and the average age was 46.3 years. A majority of providers believed ("strongly agree" or "somewhat agree") that medical cannabis was a legitimate medical therapy (58.1%) and 38.7% believed that providers should be offering to patients for managing medical conditions. A majority (> 50%) of providers believed that medical cannabis was helpful for treating the qualifying medical conditions of cancer, terminal illness, and intractable pain. A majority of providers did not know if medical cannabis was effective for managing nearly one-half of the other state designated qualifying medical conditions. Few believed that medical cannabis improved quality of life domains. Over one-third of providers believed that medical cannabis interacted with medical therapies. One-half of providers were not ready to or did not want to answer patient questions about medical cannabis, and the majority of providers wanted to learn more about it.Healthcare providers generally believe that medical cannabis is a legitimate medical therapy. Provider knowledge gaps about the effectiveness of medical cannabis for state designated qualifying conditions need to be addressed, and accurate information about the potential for drug interactions needs to be disseminated to address provider concerns. Clinical trial data about how medical cannabis improves patient quality of life domains is desperately needed as this information can impact clinical decision-making.

Tobacco smoking among those seeking treatment for cannabis use disorder (CUD) is common and is a negative predictor of cannabis outcomes. Quitting tobacco may be beneficial for those seeking to quit cannabis use. This initial proof of concept, controlled trial was designed to compare a simultaneous versus sequential tobacco intervention among those seeking treatment for CUD. Sixty-seven adults received either a simultaneous (SIM) or sequential (SEQ) approach to tobacco cessation in the context of outpatient treatment for CUD. A tobacco intervention (TI) that combined web-based counseling with nicotine replacement therapy (NRT) was provided during weeks 1-12 for SIM and was delayed until weeks 13-24 for SEQ. During weeks 1-12, no between-condition significant differences were observed on treatment participation or cannabis use outcomes. The majority of SIM participants initiated TI counseling (62%), 50% made at least one quit attempt and 41% initiated NRT. Interestingly, 39% in SEQ made tobacco quit attempts and 18% initiated NRT on their own before the TI was offered to them. However, only 30% of those in SEQ continued treatment during weeks 13-24, which compromised between-condition comparisons following the TI, but illustrated a potential clinical concern with delaying the TI. Tobacco cessation outcomes generally were poor and did not differ between conditions. This initial controlled trial suggests that addressing tobacco use during CUD treatment is acceptable and generates action towards tobacco cessation. Additional trials testing more intensive TI models may be necessary to identify more efficacious interventions for co-use of cannabis and tobacco.

Synthetic cannabinoid use disorder is emerging as a significant clinical issue. This article provides the general psychiatrist with an overview of the physical and psychiatric adverse effects of chronic synthetic cannabinoid use, as well as specific clinical responses.We performed electronic searches of Ovid MEDLINE and Ovid Embase to identify key articles, of all methodological designs, published up to June 2018.The available evidence suggests that, compared to cannabis, use of synthetic cannabinoids is associated with the more rapid development of dependence, increased psychiatric risks and complex withdrawal, and serious physical adverse effects that include seizures, cardiotoxicity and death, denoting a potential need for more intensive management.When synthetic cannabinoid use is identified, along with management of acute physical and psychiatric adverse effects, psychotherapeutic strategies to reduce use and/or harm are recommended.

Epidemiological and experimental models have been applied to describe the disproportionately high prevalence of tobacco use in patients with mental illness. This observed association has become a dire public health concern. The main objective of the present study was to examine the provision of tobacco treatment strategies in a community teaching hospital serving a predominantly underserved African American population.The study was designed as a retrospective review of eight hundred and thirty patients admitted to the inpatient psychiatric units.52.2% of the entire cohort described themselves as current smokers. Gender, primary psychiatric diagnosis, and urine toxicology showed significant differences in the tobacco smoking and nontobacco smoking groups (P<0.05). Almost all current tobacco smokers (91.9%) had tobacco cessation counseling during the course of their hospitalization, but only 64% were offered treatments for tobacco dependence. More than half (57.9%) of the 680 participants who had urine toxicology reports were positive for any illicit substance with cannabis and cocaine being the most frequently used (32.4% and 23.2%). Direct logistic regression revealed gender, psychiatric diagnosis, and substance use as the only significant predictors of tobacco smoking among our cohort (P= 0.021, 0.001, and 0.001, respectively).Tobacco screening, cessation counseling, and treatment continue to be a challenge in community psychiatric hospitals and need increased focus in the comprehensive management of patients with psychiatric disorders. The strong association between tobacco smoking and other substance use lends itself to the hypothesis that tobacco smoking debut prevention may be an effective public health strategy for addressing illicit drug use.

The aim of the study was to determine relationships between the selected DRD2 gene polymorphisms and drug addiction.One hundred drug abusers undergoing treatment were recruited from the inpatient psychiatric centers in Poland. All participants were screened by means of the clinical interview SSAGA to describe the clinical picture. In the second part of the study, participants were examined using psychometric tools assessing selected psychopathological features. After that, blood samples were collected for a DNA isolation. The following DRD2 single nucleotide polymorphisms (SNPs) of the dopamine gene were genotyped: rs1800498 polymorphism of DRD2 gene (NC_000011.10:g.113420866G>A, GRCh38.p7); rs1079597 polymorphism of DRD2 gene (NC_000011.10:g.113425564C>T, GRCh38.p7); rs1076560 polymorphism of DRD2 gene (NC_000011.10:g.113412966C>A, GRCh38.p7).The rs1800498 polymorphism has shown an association with drug abuse in which a higher frequency of the allelic T form was observed in the whole group of patients and selected subgroups with concomitant opiates or cannabis abuse history when compared with the controls.In the presented study, one of selected polymorphisms of DRD2 gene, revealed to be correlated with substance use disorder (at the limit of statistical significance), which could suggest its impact on dependence endophenotype. The presented research was a pilot study, so it requires replication on a larger group of patients to verify and confirm obtained outcomes.

The articles have been again selected among more than 15 000 abstracts and the review aims to be generalist. Interest of honey in head and neck pathologies, apnea syndrome, tonsillectomy and immunotherapy. In otology, middle ear infections and mastoiditis, cochlear implant in the elderly, deafness in children, auto-evaluation of audition and new perspectives regarding ciliar cell cultures. In rhinology the interest of different treatments including Xylitol, new technologies and nasal bleeding. In laryngology and thyroid surgery, guidelines for dysphonia, the interest of ultrasound in vocal cord evaluation and relation between thyroid surgery outcomes and training. HPV will be largely discussed as well as immunotherapy, interest of cannabis in cancer patients. Regarding salivary glands sialendoscopy, rerouting of salivary ducts and multiple detection of diseases in saliva.

Mindfulness meditation and cognitive-behavioral therapy are more cost-effective than conventional management of chronic low back pain. Women with iron deficiency can be treated with oral iron substitution every other day to improve tolerance. Smokers who smoke four or less cigarettes per day have a disproportionately high risk of cardiovascular and cerebrovascular events. All antidepressants are effective in cases of severe depression. Cannabis derivatives have no analgesic effect and do not improve the quality of life of people with neuropathic pain. Cognitive training is effective in cases of mild cognitive impairment. Delegated medical protocols can aid with blood pressure control in hypertensive patients. Nitrofurantoin is the antibiotic of choice for uncomplicated cystitis.

Pain is one reason some rheumatology patients may consider use of medical cannabis, a product increasingly perceived as a safe and neglected natural treatment option for many conditions. Legalization of recreational cannabis in Canada will promote access to cannabis. Physicians must therefore provide patients with the best evidence-based information regarding the medicinal effects and harm of cannabis.The Canadian Rheumatology Association (CRA) mandated the development of a position statement for medical cannabis and the rheumatology patient. The current literature regarding the effects of medical cannabis for rheumatology patients was assessed, and a pragmatic position statement to facilitate patient care was developed by the Therapeutics Committee of the CRA and approved by the CRA board.There are no clinical trials of medical cannabis in rheumatology patients. Evidence is insufficient about the benefit of pharmaceutical cannabinoids in fibromyalgia, osteoarthritis, rheumatoid arthritis, and back pain, but there is evidence of a high risk of harm. Extrapolating from other conditions, medical cannabis may provide some symptom relief for some patients. Short-term risks of psychomotor effects can be anticipated, but longterm risks have not been determined and are of concern.Despite lack of evidence for use of medical cannabis in rheumatology patients, we acknowledge the need to provide empathetic and pragmatic guidance for patient care. This position statement aims to facilitate the dialogue between patients and healthcare professionals in a mutually respectful manner to ensure harm reduction for patients and society.

Primary care is an important part of the care pathway for patients with psychosis; therefore, primary care physicians need to be able to accurately identify those at clinical high risk of psychosis. The difficulty of this task is increased because clinical high-risk symptoms are frequently nonspecific to psychosis.To determine whether the consultation patterns for a prespecified set of symptoms can be used to identify primary care patients who later developed a psychotic illness.This nested case-control study used primary care consultation data collected from 530 primary care practices in 13 UK regions from January 1, 2000, through September 30, 2009. Participants included 11 690 adults with a diagnosis of psychosis and 81 793 control participants who did not have a diagnosis of psychosis individually matched by age group, sex, and primary care practice. Data were analyzed from July 1, 2015, through June 2, 2017.Prespecified symptoms selected from literature included attention-deficit/hyperactivity disorder-like symptoms, bizarre behavior, blunted affect, problems associated with cannabis, depressive symptoms, role functioning problems, social isolation, symptoms of mania, obsessive-compulsive disorder-like symptoms, disordered personal hygiene, sleep disturbance, problems associated with cigarette smoking, and suicidal behavior (including self-harm).Case (diagnosis of psychosis) or control (no diagnosis of psychosis) status. Conditional logistic regression was used to investigate the association between symptoms and case-control status in the 5 years before diagnosis. Positive predictive values (PPVs) were calculated using the Bayes theorem for symptoms stratified by age group and sex. Repeated-measures Poisson regression was used to investigate symptom consultation rate.Of the total sample of 93 483 participants, 57.4% were female and 40.0% were older than 60 years (mean [SD] age, 51.34 [21.75] years). Twelve symptoms were associated with a later psychotic diagnosis (all prespecified symptoms except disordered personal hygiene). The strongest association was with suicidal behavior (odds ratio [OR], 19.06; 95% CI, 16.55-21.95). Positive predictive values were heterogeneous across age and sex. The highest PPVs were for suicidal behavior (33.0% in men 24 years or younger [95% CI, 24.2%-43.2%] and 19.6% in women aged 25-34 years [95% CI, 13.7%-27.2%]). Pairs of symptoms were associated with an increase in PPV. Consultation rates were higher in cases and increased 3 months before diagnosis.Most of the preselected nonspecific symptoms were associated with a later psychotic diagnosis, particularly among young men consulting for suicidal behavior, especially if consulting with increasing frequency. These symptoms should alert physicians to patients who may benefit from a further assessment of psychotic symptoms.

Vaporization is an increasingly popular method for cannabis administration, and policy changes have increased adult access to cannabis drastically. Controlled examinations of cannabis vaporization among adults with infrequent current cannabis use patterns (>30 days since last use) are needed.To evaluate the acute dose effects of smoked and vaporized cannabis using controlled administration methods.This within-participant, double-blind, crossover study was conducted from June 2016 to January 2017 at the Behavioral Pharmacology Research Unit, Johns Hopkins University School of Medicine, and included 17 healthy adults. Six smoked and vaporized outpatient experimental sessions (1-week washout between sessions) were completed in clusters (order counterbalanced across participants); dose order was randomized within each cluster.Cannabis containing Δ9-tetrahydrocannabinol (THC) doses of 0 mg, 10 mg, and 25 mg was vaporized and smoked by each participant.Change from baseline scores for subjective drug effects, cognitive and psychomotor performance, vital signs, and blood THC concentration.The sample included 17 healthy adults (mean [SD] age, 27.3 [5.7] years; 9 men and 8 women) with no cannabis use in the prior month (mean [SD] days since last cannabis use, 398 [437] days). Inhalation of cannabis containing 10 mg of THC produced discriminative drug effects (mean [SD] ratings on a 100-point visual analog scale, smoked: 46 [26]; vaporized: 69 [26]) and modest impairment of cognitive functioning. The 25-mg dose produced significant drug effects (mean [SD] ratings, smoked: 66 [29]; vaporized: 78 [24]), increased incidence of adverse effects, and pronounced impairment of cognitive and psychomotor ability (eg, significant decreased task performance compared with placebo in vaporized conditions). Vaporized cannabis resulted in qualitatively stronger drug effects for most pharmacodynamic outcomes and higher peak concentrations of THC in blood, compared with equal doses of smoked cannabis (25-mg dose: smoked, 10.2 ng/mL; vaporized, 14.4 ng/mL). Blood THC concentrations and heart rate peaked within 30 minutes after cannabis administration and returned to baseline within 3 to 4 hours. Several subjective drug effects and observed cognitive and psychomotor impairments persisted for up to 6 hours on average.Vaporized and smoked cannabis produced dose-orderly drug effects, which were stronger when vaporized. These data can inform regulatory and clinical decisions surrounding the use of cannabis among adults with little or no prior cannabis exposure.ClinicalTrials.gov Identifier: NCT03676166.

Cannabis legalization and commercialization have introduced novel alternative cannabis products, including edible and vaporized cannabis that might appeal to youth and be associated with polyuse (ie, use of ≥2 different products).To investigate the prevalence, patterns, and sociodemographic correlates of cannabis product use across combustible, edible, and vaporized administration methods, including polyuse of cannabis via multiple administration methods.This cross-sectional survey study included 10th-grade students from 10 Los Angeles, California, area high schools from January 2 through October 6, 2015. Students were recruited from respondents in the Happiness and Health Study, an ongoing prospective cohort study in the 10 high schools. Students not in school during administration of the pencil-and-paper survey completed abbreviated surveys by telephone, internet, or mail. Data were analyzed from July 17, 2017, through July 12, 2018.Self-reported sex, race/ethnicity, and socioeconomic status (SES). Students with high SES had parents who attained college or a higher educational level and were ineligible for free or subsidized lunch; those with low SES had parents with lower educational attainment or were eligible for free or subsidized lunch.Self-report of ever use (yes or no) and past 30-day use (yes or no) status and frequency of use (days in past 30 days) of combustible, edible, and vaporized cannabis.The sample included 3177 tenth-grade students (93.5% of study enrollees); among these students, 1715 (54.0%) were girls and the mean (SD) age was 16.1 (0.4) years. Among those with available demographic data, respondents were diverse in race/ethnicity (537 [17.2%] Asian; 149 [4.8%] black; 1510 [48.3%] Hispanic; 507 [16.2%] white; 207 [6.6%] multiethnic/multiracial; and 216 [6.9%] other) and included 1654 (60.1%) with a low SES. Prevalence of ever use was highest for combustible products (993 [31.3%]), followed by edible (676 [21.3%]) and vaporized (333 [10.5%]) products. A similar pattern was found for past 30-day use (426 [13.4%] for combustible, 249 [7.8%] for edible, and 156 [4.9%] for vaporized cannabis). Among participants who reported using cannabis in the past 30 days, mean frequency of use of combustible cannabis was higher by 2.65 days (95% CI, 1.40-3.91 days, P = .001) than the mean frequency of use for edible cannabis and 1.75 days higher (95% CI, 0.59-2.90 days, P = .003) than frequency of use for vaporized cannabis. Most cannabis users (665 [61.7%]) used multiple administration methods, and 260 (8.2%) used all 3 methods. Boys had higher prevalence of ever use for vaporized (170 [11.6%] vs 163 [9.5%]) but not combustible (459 [31.4%] vs 534 [31.1%]) or edible (303 [20.7%] vs 373 [21.7%]) cannabis. Respondents with low SES had higher prevalence of ever use for combustible (614 [37.1%] vs 242 [22.0%]) and edible (408 [24.7%] vs 166 [15.1%]) but not vaporized (186 [11.2%] vs 93 [8.5%]) cannabis.Among 10th-grade students in Los Angeles, use of cannabis via alternative administration methods was of appreciable prevalence, predominately reported in conjunction with other cannabis products and unequally distributed across sociodemographic strata. Prevention programs and regulatory restrictions addressing the spectrum of cannabis products might benefit pediatric public health.

Worldwide, cannabis is one of the most widely used psychoactive substances and cannabis use has been implicated in poorer performance in several cognitive domains, including working memory (WM). However, the neural mechanisms underlying these WM decrements are not well understood and the current study investigated the association of cannabis involvement with WM performance and associated neural activation in the Human Connectome Project (N = 1038). Multiple indicators of cannabis involvement were examined in relation to behavioral performance and brain activity in a visual N-back task using functional magnetic resonance imaging. A positive urine drug screen for tetrahydocannabinol (THC+ status), the principal psychoactive constituent in cannabis, was associated with worse WM performance and differential brain response in areas previously linked to WM performance. Furthermore, decreases in blood-activation-level-dependent (BOLD) signal in WM task-positive brain regions and increases in task-negative regions mediated the relationship between THC+ status and WM performance. In contrast, WM performance and BOLD response during the N-back task were not associated with total lifetime cannabis use, age of first use, or other indicators of involvement, suggesting that the effects of cannabis on WM were short-term residual effects, rather than long-term persistent effects. These findings elucidate differential influences of cannabis involvement on neurocognition and have significant potential implications for occupational performance in diverse settings.

The term "cross-faded," observed in focus groups and on a variety of websites, appears to refer to overlapping drug effects of multiple substances used at the same time, particularly alcohol and marijuana. This study explores young adult understanding of the cross-faded terminology in order to inform substance use research and intervention. Young adult participants (N=807, ages 18-23) in the screening survey for Project Transitions based in Seattle, WA were asked whether they had heard of being cross-faded, what they thought it meant, and how desirable and risky they thought it was. Cross-faded was a commonly understood term (87% had heard of it), most often described as using alcohol and marijuana simultaneously (43%) and second most as being both drunk and high (25%), specifically. Being cross-faded was seen as moderately risky and not desirable by most, although 18.2% described it as moderately or very desirable. Risk factor differences in perceptions of being cross-faded were found for sex, college status, and alcohol and marijuana use. Cross-faded is a common term for the effects of using multiple substances. As such it merits further research consideration with the aim of optimizing the effectiveness of surveys and programming.

The present review will provide an overview of the neurobiology, epidemiology, clinical impact, and treatment of cannabis use disorder (CUD) in mood disorders.Patients with mood disorders including major depressive disorder (MDD) and bipolar disorder (BD) have higher rates of cannabis use, and CUD compared to the general population. Reasons for this association are not clear, nor are the putative therapeutic effects of cannabis use, or its components delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), in these illnesses. The evidence surrounding treatments for patients with this comorbidity is lacking, with more support for psychotherapeutic treatments compared with pharmacological treatments.Cannabis use may be associated mood disorders, but more research is needed to increase our understanding of the mechanisms for this association, and to develop more effective treatments for this comorbidity.

This review highlights advances made in recent years in the diagnosis and management of acute pancreatitis (AP). We focus on epidemiological, clinical, and management aspects of AP. Additionally, we discuss the role of using risk stratification tools to guide clinical decision making. The majority of patients suffer from mild AP, and only a subset develop moderately severe AP, defined as a pancreatic local complication, or severe AP, defined as persistent organ failure. In mild AP, management typically involves diagnostic evaluation and supportive care resulting usually in a short hospital length of stay (LOS). In severe AP, a multidisciplinary approach is warranted to minimize morbidity and mortality over the course of a protracted hospital LOS. Based on evidence from guideline recommendations, we discuss five treatment interventions, including intravenous fluid resuscitation, feeding, prophylactic antibiotics, probiotics, and timing of endoscopic retrograde cholangiopancreatography (ERCP) in acute biliary pancreatitis. This review also highlights the importance of preventive interventions to reduce hospital readmission or prevent pancreatitis, including alcohol and smoking cessation, same-admission cholecystectomy for acute biliary pancreatitis, and chemoprevention and fluid administration for post-ERCP pancreatitis. Our review aims to consolidate guideline recommendations and high-quality studies published in recent years to guide the management of AP and highlight areas in need of research.

The increased use of cannabis among adults and the general perception that cannabis is harmless has been accompanied by a rise in the number of acute poisoning cases among children. We present a retrospective, descriptive study of patients aged 3 years or younger who were treated for cannabis poisoning in a pediatric emergency department between 2012 and 2017. Epidemiologic and clinical data as well as toxicologic findings are reported. We found 10 cases of cannabis poisoning in our records. Nine of the patients had diminished consciousness. Only 2 families initially reported exposure to cannabis when interviewed. Repeated exposure was demonstrated by analysis of hair from 2 patients. We conclude that cannabis poisoning should be included in the differential diagnosis of young children with acute neurologic symptoms of unknown origin. When cannabis is detected in urine samples collected in the pediatric emergency department, more specific diagnostic techniques should be used to assess the possibility of repeated exposure.

In recent years e-liquids used in electronic cigarettes have become an attractive alternative to smoking tobacco. A new trend is the use of e-liquids containing synthetic cannabinoids (SCs) instead of smoking cannabis or herbal mixtures laced with SCs. In the frame of a systematic monitoring of the online market of 'legal high' products, e-liquids from online retailers who also sell herbal blends were bought.The products were analyzed by gas chromatography-mass spectrometry. In some of the e-liquids an unknown compound was detected which was identified as the SC 5F-Cumyl-PINACA (1-(5-fluoropentyl)-N-(2-phenylpropan-2-yl)-1H-indazole-3-carboxamide) by nuclear magnetic resonance analysis. To investigate the phase I metabolism of this new class of compounds, 5F-Cumyl-PINACA and its non-fluorinated analog Cumyl-PINACA were incubated with pooled human liver microsomes (pHLM). Cumyl-PINACA was additionally ingested orally (0.6 mg) by a volunteer in a controlled self-experiment. To assess the relative potency of Cumyl-PINACA a set of SCs were characterized using a cAMP assay.Metabolism of 5F-Cumyl-PINACA and Cumyl-PINACA showed similarities with AM-2201 and JWH-018. The main metabolites were formed by hydroxylation at the N-pentyl side chain. The main metabolites detected in the volunteer's urine sample were the same as in the pHLM assay. All SCs tested with the cAMP assay were full agonists at the CB1 receptor. Cumyl-PINACA was the most potent SC among the tested compounds and showed an EC50 value of 0.06 nM.The increasing popularity of e-liquids particularly among young people, and the extreme potency of the added SCs, pose a serious threat to public health. To our knowledge, this is the first report describing the tentative identification of human in vivo metabolites of Cumyl-PINACA and 5F-Cumyl-PINACA.

The aim of the study is to describe the prevalence of illicit drug use in England and Wales using data from the UK Survey of Non-Medical Use of Prescription Drugs (NMURx) programme and to compare against the well-established Crime Survey England and Wales (CSEW). The rationale is that recreational and illicit drug use is common, but the prevalence is difficult to estimate with personal interviewing methods.We compared two cross-sectional population surveys (NMURx, n=8903 and CSEW, n=20 685) with data regarding self-reported recreational drug use and demographics. NMURx is an online survey using non-probability sampling methodology with preset demographical quotas based on census data. CSEW surveys drug use via computer-assisted self-interviewing as part of a computer-assisted personal-interviewing crime survey.Cannabis was the most frequently used drug regardless of demographics. Prevalence of drug use for specific substances was generally higher for males, younger ages and students. The relationship between income and drug misuse is less clear. Self-reported prevalence of drug use in the NMURx survey is consistently higher than CSEW (absolute difference 1%-3 % across substances and timescales) and persists after stratification for gender, age, student status and household income.The NMURx survey has a broad reach of participants, and a sampling scheme that achieves external validity, compared with general population demographics. NMURx's online format allows flexibility in items surveyed and in response to emerging trends. The self-reported drug use in the NMURx cohort is comparable, although slightly higher, than the CSEW estimates.

New drugs available in a click, plethora of games, new regulations on cannabis, addiction medicine has a lot to do ! In 2018, Switzerland recognized a training certificate in addiction medicine, pathological gambling entered into ICD-11 and vaping, first considered with suspicion, found a place in the pharmacopoeia of the fight against tobacco. That's not all, on the alcohol front, we realized that even a small glass can hurt and the medicine of addictions evolved towards models of recovery that aim to improve quality of life with chronic diseases. Finally, the American opioid prescription epidemic is worrying in Switzerland, even if the situation and the context are very different.

The use of cannabis for recreational purposes has increased worldwide, and the proportion of cannabis users in the adolescent population is high. Susceptibility to cannabis use involves various factors, including childhood adversity; however, the effects of different types of violence on cannabis use have not been evaluated. The aim of this review was to analyze the effects of different types of violence on cannabis use in adolescence. We searched electronic databases (PubMed, Science Direct, Web of Science, Ovid and CONRICyT) using the following algorithm: (("Cannabis" OR "Marijuana Smoking" OR "Marijuana Abuse") AND ("Child Abuse" OR "Domestic Violence" AND "Adolescent")), considering all articles published up to November 3th, 2017. Odds ratios (ORs) were calculated for the effects of experiencing different types of violence during childhood on cannabis use. Six studies, representing 10 843 adolescents of both sexes, were ultimately included in the systematic review and meta-analysis. Three types of early-life adversity were associated with cannabis abuse/dependence: physical abuse (OR: 1.58, 95% CI [1.01-2.46]), sexual abuse (OR: 2.35, 95% CI [1.64-3.35]), and witnessing violence (OR: 3.22, 95% CI [0.63-16.54]). The results indicated that two specific types of child maltreatment, sexual and physical abuse, were critical factors affecting vulnerability to cannabis use in adolescence. The number of studies examining other types of violence was limited. The results highlighted the importance of enhancing efforts to prevent violence, particularly sexual abuse, as part of integral programs designed to prevent cannabis abuse and dependence.

This study evaluated the patterns of substance use in a large sample of male-to-female (MtoF) and female-to-male (FtoM) transsexuals. A total of 251 transsexual subjects (163 MtoF and 88 FtoM), attended in the Catalonia Gender Unit, completed self-administrated questionnaires on consumption of alcohol, tobacco, cannabis, cocaine, opioids, and designer drugs. Results were compared with the general population in Catalonia using data from the National Health Service (EDADES 2013 study). Current consumption of alcohol (70.1%), tobacco (46.2%), and cannabis (16.3%) among transsexuals was similar when compared with men (72.1%, 42.1%, 12.8%) and increased when compared with women (57.6%, 35.2%, 5%); the consumption between MtoF and FtoM subgroups was similar.  The use of cocaine was almost ten times more prevalent in the MtoF subgroup than in the FtoM subgroup (1.1%), and in general population (less than 1%).  Only a few reported uses of opioids and designer drugs. In conclusion, the substance use among transsexuals, except for the use of cocaine, was similar between MtoF and FtoM subgroups, and resembled the consumption prevalence among men in the general population. The proportion of cocaine consumers in the MtoF subgroup was up to ten times higher than in other subgroups.

Communities That Care (CTC) is a prevention system aimed at reducing antisocial behaviors in adolescents. In Colombia, this system has been developed and adapted under the name of Comunidades Que se Cuidan (CQC). Successful implementation of CQC depends on valid associations between measured risk and protective factors (RPFs) for substance use and substance use outcomes. This study assessed these associations using large-scale, school-based surveys of Colombian youth. A cross-sectional analysis was performed. Data from 23 communities in Colombia were collected between 2012 and 2016 from young people (N = 50,946) aged 10 to 19 years. Dichotomous alcohol, cigarette, cannabis, and other illegal drug use outcomes were assessed for past 30-day, past-year, and lifetime use. Logistic regression analyses, adjusting for age, gender, and age by RPF, and gender by RPF interactions, were performed for each RPF. All the associations of the 14 RPF evaluated were statistically significant (p < .001). Regarding observed effect sizes, 3.0% were considered very small (0.70 ≥ OR ≤ 1.43), 51.7% small (0.70 ≥ OR ≥ 1.43), 42.6% medium (0.40 ≥ OR ≥ 2.48) and 7.1% large (0.23 ≥ OR ≥ 4.27). Significant main effects for age and gender, and their interactions with RPFs were found for most RPFs. Findings from this study demonstrate the viability of RPFs for adolescent substance use as focal points for intervention planning, development, and evaluation of community-based prevention systems like CQC that rely on epidemiologic data for local decision making.

The aim of the present study was to retrospectively study the onset and progression sequence of the most frequent pathways of drug use initiation in a sample of the Spanish general population. Data come from the 2011 household survey on drug use in Catalonia, Spain, on non-institutionalized individuals aged 15-64 in the general population. The final sample was of 2,069 individuals and had the same age distribution as the general population. Progressions of drug initiation were pictured by quantifying transitions from a previous state in terms of the number of individuals and weighted percentages. Survival analyses were employed to assess the most prevalent pathways found in the descriptive analysis using additive regression models. Median ages of onset were decreasing in every cohort from 1965 to 1985-1996: from 17 to 15 in tobacco, 20 to 16 in cannabis and 21 to 18 in cocaine. In people who consumed the three drugs studied, the most frequent pathway was "tobacco-daily tobacco-cannabis-cocaine". These results demand health policies and prevention strategies in order to increase perception of the risks of legal and illegal substances. This, together with well-designed peer interventions could reduce the risk of exposure to illegal drugs such as cannabis and cocaine, thus reducing the likelihood of future problem drug use.

Strict adherence to antiretroviral treatment (ART) is needed to ensure the effectiveness of HIV treatment. The adverse effects of substance abuse and neurocognitive impairment on medication adherence have both been suggested by several studies. Therefore, the aim of this research is to study the relationship among adherence to ART, cognitive dysfunction, and abuse of certain substances (alcohol, heroin, cocaine, other stimulants, cannabis and benzodiazepines) and/or methadone treatment in our social environment. We performed an observational case-control study with a sample of 125 HIV+ patients, who were classified as patients with poor adherence (cases) and subjects with adequate compliance (controls). Adherence was defined by the Hospital Pharmacy and verified with the Simplified Medication Adherence Questionnaire (SMAQ) and the reference physician's clinical impression. Cognitive functioning was measured with the Zoo Map Test and Trail Making Test (TMT). Substance abuse was collected through a semi-structured clinical interview protocol. Statistical analysis was made using a binary logistic regression model. The results indicate that both alcohol abuse and neurocognitive impairment measured by Zoo Map Test were significantly associated with poorer adherence to ART. No significant association was found between adherence and other substance use, or between adherence and TMT score. Screening of cognitive impairment measured by the Zoo Map Test and alcohol abuse may lead to the development of strategies to improve de adherence to ART in HIV+ patients.

In the last decades, a lot of attention has been paid to the compounds present in medicinal Cannabis sativa L., such as Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD), and their effects on inflammation and cancer-related pain. The National Cancer Institute (NCI) currently recognizes medicinal C. sativa as an effective treatment for providing relief in a number of symptoms associated with cancer, including pain, loss of appetite, nausea and vomiting, and anxiety. Several studies have described CBD as a multitarget molecule, acting as an adaptogen, and as a modulator, in different ways, depending on the type and location of disequilibrium both in the brain and in the body, mainly interacting with specific receptor proteins CB1 and CB2. CBD is present in both medicinal and fibre-type C. sativa plants, but, unlike Δ9-THC, it is completely nonpsychoactive. Fibre-type C. sativa (hemp) differs from medicinal C. sativa, since it contains only few levels of Δ9-THC and high levels of CBD and related nonpsychoactive compounds. In recent years, a number of preclinical researches have been focused on the role of CBD as an anticancer molecule, suggesting CBD (and CBD-like molecules present in the hemp extract) as a possible candidate for future clinical trials. CBD has been found to possess antioxidant activity in many studies, thus suggesting a possible role in the prevention of both neurodegenerative and cardiovascular diseases. In animal models, CBD has been shown to inhibit the progression of several cancer types. Moreover, it has been found that coadministration of CBD and Δ9-THC, followed by radiation therapy, causes an increase of autophagy and apoptosis in cancer cells. In addition, CBD is able to inhibit cell proliferation and to increase apoptosis in different types of cancer models. These activities seem to involve also alternative pathways, such as the interactions with TRPV and GRP55 receptor complexes. Moreover, the finding that the acidic precursor of CBD (cannabidiolic acid, CBDA) is able to inhibit the migration of breast cancer cells and to downregulate the proto-oncogene c-fos and the cyclooxygenase-2 (COX-2) highlights the possibility that CBDA might act on a common pathway of inflammation and cancer mechanisms, which might be responsible for its anticancer activity. In the light of all these findings, in this review we explore the effects and the molecular mechanisms of CBD on inflammation and cancer processes, highlighting also the role of minor cannabinoids and noncannabinoids constituents of Δ9-THC deprived hemp.

Cannabis is one of the most important industrial crops distributed worldwide. However, the phylogeographic structure and domestication knowledge of this crop remains poorly understood. In this study, sequence variations of five chloroplast DNA (cpDNA) regions were investigated to address these questions. For the 645 individuals from 52 Cannabis accessions sampled (25 wild populations and 27 domesticated populations or cultivars), three haplogroups (Haplogroup H, M, L) were identified and these lineages exhibited distinct high-middle-low latitudinal gradients distribution pattern. This pattern can most likely be explained as a consequence of climatic heterogeneity and geographical isolation. Therefore, we examined the correlations between genetic distances and geographical distances, and tested whether the climatic factors are correlated with the cpDNA haplogroup frequencies of populations. The "isolation-by-distance" models were detected for the phylogeographic structure, and the day-length was found to be the most important factor (among 20 BioClim factors) that influenced the population structures. Considering the distinctive phylogeographic structures and no reproductive isolation among members of these lineages, we recommend that Cannabis be recognized as a monotypic genus typified by Cannabis sativa L., containing three subspecies: subsp. sativa, subsp. Indica, and subsp. ruderalis. Within each haplogroup which possesses a relatively independent distribution region, the wild and domesticated populations shared the most common haplotypes, indicating that there are multiregional origins for the domesticated crop. Contrast to the prevalent Central-Asia-Origin hypothesis of C. saltiva, molecular evidence reveals for the first time that the low latitude haplogroup (Haplogroup L) is the earliest divergent lineage, implying that Cannabis is probably originated in low latitude region.

Drug addiction is a chronic neuropsychiatric disorder that escalates from an initial exposure to drugs of abuse, such as cocaine, cannabis, or heroin, to compulsive drug-seeking and intake, reduced ability to inhibit craving-induced behaviors, and repeated cycles of abstinence and relapse. It is well-known that chronic changes in the brain's reward system play an important role in the neurobiology of addiction. Notably, environmental factors such as acute or chronic stress affect this system, and increase the risk for drug consumption and relapse. Indeed, the HPA axis, the autonomic nervous system, and the extended amygdala, among other brain stress systems, interact with the brain's reward circuit involved in addictive behaviors. There has been a growing interest in studying the molecular, cellular, and behavioral mechanisms of stress and addiction in Latin-America over the last decade. Nonetheless, these contributions may not be as strongly acknowledged by the broad scientific audience as studies coming from developed countries. In this review, we compile for the first time a series of studies conducted by Latin American-based neuroscientists, who have devoted their careers to studying the interaction between stress and addiction, from a neurobiological and clinical perspective. Specific contributions about this interaction include the study of CRF receptors in the lateral septum, investigations on the neural mechanisms of cross-sensitization for psychostimulants and ethanol, the identification of the Wnt/β-catenin pathway as a critical neural substrate for stress and addiction, and the emergence of the cannabinoid system as a promising therapeutic target. We highlight animal and human studies, including for instance, reports coming from Latin American laboratories on single nucleotide polymorphisms in stress-related genes and potential biomarkers of vulnerability to addiction, that aim to bridge the knowledge from basic science to clinical research.

In contrast to several studies that examined different domains of neurocognitive functions in long-term abstinent cannabis users, there are few studies examined impulsivity in cannabis users with prolonged abstinence. The aim of this study was to test whether impulsivity and sensation seeking traits and impulsive decision-making are transient or enduring in patients with cannabis dependence who were abstinent for at least 1 month.The study included 30 patients with cannabis dependence (CDP) who had been abstinent for at least 1 month and 30 healthy controls. All the participants were male and the two groups were matched for age and duration of education.As a result of Iowa Gambling Task (IGT) evaluation, there was no significant group (CDP vs. control) by block interaction in IGT performance (p=0.680). CDP showed significantly higher Barratt Impulsiveness Scale-11 (BIS-11) total (p=0.006), BIS-11 non-planning (p=0.006) and Zuckerman Sensation Seeking Scale experience seeking subscale (p=0.001) scores compared with controls.This is the first study to investigate decision-making, self-report impulsivity and sensation seeking in long-term abstinent CDP. Our findings suggest that both self-report impulsivity and experience seeking may reflect a stable trait in CDP but not deficits on decision-making. This suggestion is consistent with the hypothesis that elevated impulsivity and sensation seeking traits may lead to addiction when they occur together rather than alone.

The credibility of cannabis as a source of a legitimate pharmaceutical ingredient in prescription medications took a major step forward in 2018 when the FDA approved Epidiolex (cannabidiol) for two types of severe seizures. Epidiolex was a stellar candidate for approval. It reduced convulsive seizures by about 40% and has a good safety profile.

Cannabinoids are the derivatives of the cannabis plant, the most potent bioactive component of which is tetrahydrocannabinol (THC). The most commonly used drugs containing cannabinoids are marijuana, hashish, and hashish oil. These compounds exert their effects via interaction with the cannabinoid receptors CB1 and CB2. Type 1 receptors (CB1) are localised mostly in the central nervous system and in the adipose tissue and many visceral organs, including most endocrine organs. Type 2 cannabinoid receptors (CB2) are positioned in the peripheral nervous system (peripheral nerve endings) and on the surface of the immune system cells. Recently, more and more attention has been paid to the role that endogenous ligands play for these receptors, as well as to the role of the receptors themselves. So far, endogenous cannabinoids have been confirmed to participate in the regulation of food intake and energy homeostasis of the body, and have a significant impact on the endocrine system, including the activity of the pituitary gland, adrenal cortex, thyroid gland, pancreas, and gonads. Interrelations between the endocannabinoid system and the activity of the endocrine system may be a therapeutic target for a number of drugs that have been proved effective in the treatment of infertility, obesity, diabetes, and even prevention of diseases associated with the cardiovascular system.

Increasingly, states are legalizing cannabis for recreational use. Improved accessibility may allow adults with pain to use cannabis more liberally. Greater understanding is needed about how adults with pain perceive the effects of cannabis, particularly those who also use opioid analgesics.To examine the perceived effects of cannabis among adults who have been prescribed opioids for persistent pain.A survey-based study was conducted on 150 adults with persistent pain. Data from two open-ended questions were analyzed using a qualitative descriptive approach and content analysis.Data analysis led to identification of two main categories and five subcategories: (a) cannabis benefits with two subcategories of "physiological" and "mental health"; (b) adverse effects with three subcategories of "physiological," "mental health," and "social and economic concerns."Both positive and negative effects of cannabis were described. Nursing practice, including open communication with patients, can be guided by patient perspectives surrounding benefits and adverse effects of cannabis use.

Prison mental health care is a significant topic which has been already studied and described in literature, particularly because of important implications both in the prison and in the health care system. It's not uncommon that inmates suffering from mental disorders are referred to high security forensic services (HSFS) but, to date, studies assessing factors associated with relevant referrals to these services are missing. So, the aim of our study is to investigate socio-demographic, criminological, psychopathological and toxicological variables among those who were referred to HSFS as compared to their non-referred counterpart.We conducted a cross-sectional study recruiting 159 subjects receiving prison inpatient care in an Italian jail, between January 2010 and August 2015. No subjects were excluded from the study. The mean age was 39.About half of included prisoners suffered from personality disorder while one-third from psychotic disorders. >60% of the subjects had comorbid substance use disorders. The odds of being referred to HSFS were related to previous admission (odds ratio [OR] = 5.34, 95% confidence interval [CI] 1.66-17.16), diagnosis of psychosis (OR = 2.79, 95% CI 1.11-7.04) and cannabis use disorder (OR = 2.68, 95% CI 1.14-6.28). Personality disorder was inversely associated to the referral to forensic facilities (OR = 0.37, 95% CI 0.14-0.97).Mental health services should improve preventive measures for vulnerable prisoners in order to reduce criminal recidivism and forensic readmission.

To review the efficacy, safety, pharmacology and pharmacokinetics of pure, plant-derived cannabidiol (CBD; Epidiolex) in the treatment of Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS).Relevant information was identified through EMBASE and Ovid MEDLINE (1946 to October 2018). Product labeling and https://www.clinicaltrials.gov were also reviewed.English language articles evaluating efficacy and safety in humans with treatment-resistant epilepsies were reviewed; additional pharmacology and pharmacokinetic studies in humans, animals, and in vitro were also included.Pure, plant-based CBD is a pharmaceutical grade extract that exhibits clinically significant antiseizure properties, with a hypothesized multimodal mechanism of action. In the GWPCARE trial series, CBD displayed superior efficacy in reducing key seizure frequencies (convulsive seizures in DS; drop seizures in LGS) by 17% to 23% compared with placebo as adjunctive therapy to standard antiepileptic drugs in patients 2 years of age and older. Common adverse effects were somnolence, diarrhea, and elevated hepatic transaminases. Noteworthy drug-drug interactions included clobazam, valproates, and significant inducers/inhibitors of CYP2C19 and 3A4 enzymes. Relevance to Patient Care and Clinical Practice: A discussion regarding CBD dosing, administration, adverse effects, monitoring parameters, and interactions is provided to guide clinicians. CBD offers patients with DS and LGS a new treatment option for refractory seizures.This is the first cannabis-derived medication with approval from the US Food and Drug Administration. This CBD formulation significantly reduces seizures as an adjunct to standard antiepileptic therapies in patients ≥2 years old with DS and LGS and is well tolerated.

Driving under the influence of drugs (DUID) increases the risk of serious injury or death in traffic accidents. The aim of this study was to provide information about DUID in Spanish drivers.10,064 oral fluid samples were collected from Spanish drivers that tested positive on the roadside using the Dräger DrugTest 5000 (DDT5000) between 2013 and 2015. Samples were collected using Quantisal™ and analysed by LC-MS/MS at the Toxicology Laboratory of the Institute of Forensic Science of the University of Santiago de Compostela.Drivers were mainly young men (85.1% male, 29.7 ± 8.1 years old). In 98.5% of cases, LC-MS/MS results confirmed at least one of the positive results detected on the roadside. Cannabis (82.4%) and cocaine (42.1%) were the most commonly detected drugs. Poly-drug use was observed in 42.7% of drivers, mostly for all illicit drugs (>80%) except for cannabis (42.6%). Illicit drug and single-drug use was more frequent among drivers under 35 years old, and medicines and poly-drug use more common among drivers older than 35 years old. The on-site device performance was calculated using both the DDT5000 cut-offs and the LC-MS/MS method LOQs. Sensitivity (>73% vs >58%), specificity [>94% for all the compounds regardless the cut-offs used, except for cannabis (71%)] and accuracy (>87.5% with both cut-offs) fulfilled the DRUID Project requirements in all cases.LC-MS/MS confirmation result was negative in only 1.5% of the cases. The DUID driver profile was a young man, consuming cannabis or a combination of cannabis and cocaine.

Physicians are at risk of burnout, anxiety and depression. Prevention is needed from the beginning of the medical studies to detect early poor mental health outcomes.To determine the prevalence and associated of psychiatric or psychological follow-up in a national sample of undergraduate and postgraduate medical students (UPMS).UPMS of the 35 French Medicine faculties were recruited through mailing lists and social networks between December 2016 and May 2017 and fulfilled Internet anonymised questionnaires.Overall, 10,985 UPMS were included in the present study (2165 (19.7%) postgraduate, 31.6% males, mean aged 21.8 years). Overall, 1345 (12.2%) were followed-up by a psychiatrist and/or a psychologist, 20.5% of them were regular anxiolytic consumers and 17.2% of them were regular antidepressant consumers. In multivariate analyses, being followed-up by a psychiatrist and/or psychologist was associated with older age (aOR = 1.2[1.2-1.2], p < 0.0001), female gender (aOR = 0.5[0.5-0.7], p < 0.0001), current alcohol use disorder (aOR = 1.3[1.3-1.5], p < 0.0001), higher anxiolytic (aOR = 3.1[2.5-3.7],p < 0.0001) and antidepressant (aOR = 11.7[7.6-18.0],p < 0.0001) consumption, and with lower self-reported general health, social functioning and mental health quality of life (all aORs = 0.9, all p < 0.05). The UPMS followed-up by psychiatrist and/or psychologist reported to have been more frequently exposed to sexual assault (5.1% vs. 0.9%, aOR = 2.5[1.3-4.7], p < 0.0001), domestic violence (3.3% vs. 0.8% aOR = 2.1[1.2-4.0], p = 0.01) and parents divorce (11% vs. 6.4%, aOR = 1.5[1.2-1.9], p = 0.001). Students followed-up by a psychiatrist and/or psychologist reported more frequently to seek alleviating anxiety (aOR 1.9[1.6-2.3], p < 0.0001), depression (aOR 1.7[1.3-2.1],p < 0.0001), coping with studies difficulties (aOR 1.5[1.2-1.8],p < 0.0001), experiencing more stress at hospital (aOR = 2.3[1.6-3.5],p < 0.001) and more burnout syndrome (aOR = 1.4[1.1-1.8], p = 0.03).Around 12% of UPMS are followed-up by a psychiatrist and/or a psychologist. These students reported higher antidepressant and anxiolytic consumption, psychic suffering and altered quality of life, associated with professional pressure and personal issues. Public health programs should be developed to help these students through their studies to prevent later mental /addictive issues and professional suffering. Improving UPMS mental health may also improve the later quality of care of their patients and global stress at hospital.

Multiple sclerosis is a complex autoimmune disorder which characterized by demyelination and axonal loss in the central nervous system (CNS). Several evidences indicate that some new drugs and stem cell therapy have opened a new horizon for multiple sclerosis treatment, but current therapies are partially effective or not safe in the long term. Recently, herbal therapies represent a promising therapeutic approach for multiple sclerosis disease. Here, we consider the potential benefits of some herbal compounds on different aspects of multiple sclerosis disease. The medicinal plants and their derivatives; Ginkgo biloba, Zingiber officinale, Curcuma longa, Hypericum perforatum, Valeriana officinalis, Vaccinium macrocarpon, Nigella sativa,Piper methysticum, Crocus sativus, Panax ginseng, Boswellia papyrifera, Vitis vinifera, Gastrodia elata, Camellia sinensis, Oenothera biennis, MS14 and Cannabis sativa have been informed to have several therapeutic effects in MS patients.

The use of illicit drugs has become a worldwide health problem. Substances with the potential to be abused may have direct or indirect effects on physiologic mechanisms that lead to organ system dysfunction and diseases.The present study aims to investigate the structural and reabsorption integrity of the nephron among Egyptian addicts of tramadol alone and coabused with cannabis.Sixty-five males were included in the study, they were classified into control group (G1=19), tramadol addicts group (G2=18), and tramadol coabused with cannabis addicts group (G3=28). Parameters investigated for structural integrity were urinary levels ofleucineaminopeptidase and N-acetyl-β-D-glucosaminidase, and urinary parameters for reabsorption integrity were levels of copper and zinc as well as calcium, also urinary creatinine was measured. In addition, urinary levels of tramadol and tetrahydrocannabinol were estimated.Among the two addicted groups, all measured parameters were not significantly different in comparison with the control group except for urinary calcium excretion which was found to be significantly increased among the two addicted groups.Both tramadol addiction alone or coabused with cannabis causes increased urinary excretion of calcium, indicating reabsorption dysfunction of calcium without affecting structural integrity along the nephron.

Although there are a number of studies about substance use by medical students, the majority are still cross-sectional. We aimed to investigate prevalence, 2-year incidence, and factors associated with substance use during medical training.This longitudinal study included medical students in 4 different waves (with each wave equaling 1 semester). Socio-demographic data, Duke Religion Index (DUREL), DASS-21, and the "Alcohol, Smoking and Substance Involvement Screening Test" (ASSIST) were used.A total of 327 (56.2%) medical students were followed for 2 years. Prevalence of lifetime substance use was 89.9% for alcohol, 34.5% for cannabis, and 17.1% for sedatives. Tobacco had the greatest incidence of use over the 2 years (16.4%), followed by alcohol (13.8%) and cannabis (13.8%). At least 24% of the students would need an intervention for alcohol use, 11.4% for tobacco, and 6.5% for cannabis. Alcohol use during wave 4 was associated with organizational religiosity, and alcohol and tobacco use at the baseline; tobacco use during wave 4 was associated with age, non-organizational religiosity, and cannabis and tobacco use at the baseline; and cannabis use during wave 4 was associated with cannabis and tobacco use at the baseline.Our results indicate an increase in the incidence of lifetime substance use during medical training. Prior use of substance was associated with a higher chance of use after 2 years, while age and religiousness seem to reduce the chance of use.

The Cannabis Act legalized the possession and sale of nonmedical cannabis in Canada on October 17, 2018. Evaluating the impact of cannabis legalization requires a more thorough understanding than is provided by most existing measures of cannabis use. The aim of this study was to pretest a range of cannabis consumption measures used in a population-based survey and to share insights gained in the process. Cognitive interviewing was conducted among 10 cannabis users aged ≥16 years. Comprehension and self-reporting of consumption types and amounts, sources of purchase, and cannabinoid levels were examined. Findings revealed areas for improvement in a number of survey items, including unclear wording and reference images. Identified issues were used to improve the survey for use in the International Cannabis Policy Study. The authors discuss important principles (e.g., use of visual cues, user-selected units, and time frames) that should be adopted when assessing cannabis use in population-based studies.

Cannabis is the second most commonly abused illicit drug after methamphetamine in South Korea. To prove cannabis consumption, 11-nor-9-carboxy-tetrahydrocannabinol (THC-COOH), the metabolite of tetrahydrocannabinol (THC), was screened for in a hair analysis. In this study, we developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis method, which was used to analyze authentic hair samples in 2017. Possible contaminants on the surface of hair samples were eliminated by washing twice each with 2mL of methanol and distilled water. After adding an internal standard (THC-COOH-d3), the hair samples (about 20mg each) were digested with 1M NaOH, extracted twice with mixed organic solvents (n-hexane:ethyl acetate), and analyzed by an LC-MS/MS system. Identification and quantification of THC-COOH and THC-COOH-d3 were performed using a multiple reaction monitoring (MRM) mode at m/z 245 and 191 and m/z 248, respectively (quantifier ions are underlined). The following validation parameters were evaluated: selectivity, linearity, limit of detection (LOD), limit of quantification (LOQ), precision, accuracy, matrix effect, and recovery. The LOD and LOQ of the method was 0.1pg/mg. Good linearity was achieved for THC-COOH in the range from 0.1 to 20pg/mg. The method showed an acceptable precision and accuracy, both of which were less than 15% at the three concentrations of THC-COOH (0.2, 1, and 10pg/mg). THC-COOH showed ion suppression at these three concentrations. The concentrations of THC-COOH in the authentic hair samples ranged from 0.10 to 27.30pg/mg (total 586 cases), and its concentrations were classified as low, medium, or high ranges, i.e., 0.10-0.39pg/mg, 0.39-1.99pg/mg, or 1.99-27.30pg/mg, respectively, according to statistical evaluation. This method showed the possibility of replacing the existing gas chromatography-tandem mass spectrometry (GC-MS/MS) analysis. However, further development of our LC-MS/MS method is necessary in order to meet the recommended 0.05pg/mg cut-off.

Hemp (Cannabis sativa L.), traditionally cultivated for industrial use and harvested for fibers and seeds, has raised much interest as a sustainable crop in the last years. Recently, hemp seeds and derived oil have started to be used in a variety of food products. Hemp-based food products are considered less allergenic than those from other edible seeds, although this statement has never been experimentally verified. In this study high purity grade hemp flour (HF) and hemp protein isolate (HPI) were obtained through a fast and cheap process starting from defatted hemp cakes, a residue of hempseed oil extraction. HPI resulted enriched at nearly 86% protein, mainly constituted by the storage protein edestin (accounting for 70% total protein). In vitro protein digestibility was determined using a static model of gastrointestinal digestion (GID), which included a final step with purified brush border membrane (BBM) enzyme preparations. HF and HPI showed a high degree of digestibility. The survival of potential bioactive and/or allergenic peptide sequences in digests was investigated by peptidomic analysis. Only a limited number of sequences survived GID. Among them, fragments from 12 seed proteins. These fragments were precursors of sequences with potential bioactive peptides, which might justify the bioactivity of HPI hydrolysates, reported in previous studies. More importantly, all known hemp allergens, including the major thaumatin-like protein and LTP, were entirely eliminated by the HPI production process, neither fragments of the proteins were present after GID. These data support the use of HPI as an ingredient for hypoallergenic foods.

Drug consumption in individual cities, regions, and at various music events and festivals across the EU has generally been monitored via questionnaires, patients' medical data, and police reports. However, an overview of drug consumption obtained from these methods can be negatively affected by various subjective factors. We aimed to investigate an association between levels of target drugs in wastewater, music genres, and festival courses. The occurrence of illicit drugs, their metabolites, and psychoactive compounds was investigated in the influent of six wastewater treatment plants in the Czech and Slovak Republic during seven large-scale music festivals from different music genres: metal, rock, pop, country and folk, ethnic, multi-genre, dance, and trance. The total number of participants included >130,000 active festival attendees. The association between music genre and illicit drug and/or psychoactive pharmaceutical consumptions is discussed on the basis of the results obtained through wastewater analyses. The observed trend was similar to worldwide published data with a specific local phenomenon of methamphetamine prevalence that did not significantly change between music events. Increased specific loads of cocaine (measured as its metabolite benzoylecgonine) and Ecstasy, along with some cannabis, were mainly observed during pop/rock and dance music festivals. However, there was no significant increase observed in the specific loads of all monitored psychoactive pharmaceuticals. This study demonstrates that the abuse of some illicit drugs is closely associated with specific music preferences.

EVICT project has noted the increase in cannabis use in the Spanish youth population, and has studied its association with tobacco, concluding that: It has an influence in the learning to smoke process: The beginning can be combined and with bi-directional influence. It has an influence on dependence the development of dependence Their interaction is relevant in the development of dependence. It has an influence on toxicity: Smoking tobacco and cannabis generates greater problems than smoking tobacco alone. And, therefore, the EVICT team issues some considerations: Prevention considerations. Differentiate between therapeutic and recreational use. Smoking cannabis is not therapeutic nor innocuous, and can affect the development of nicotine dependence, or, less frequently, cannabis dependence. Approach and treatment considerations. In A first option of cessation of both must be proposed in people who consume tobacco and cannabis Harm Reduction. To those that only consume tobacco/cannabis: Harm Reduction programs should be more applicable to those in whom consumption is considered more problematic.

To quantify changes in (i) potency (concentration of Δ9 -tetrahydrocannabinol; %THC), (ii) price (euros/g of cannabis) and (iii) value (mg THC/euro) of cannabis resin and herbal cannabis in Europe.Repeated cross-sectional study.Data collected from 28 European Union (EU) member states, Norway and Turkey by the European Monitoring Centre for Drugs and Drug Addiction.Outcome variables were potency, price and value for cannabis resin and herbal cannabis in Europe, 2006-16. Inflation was estimated using the Harmonised Indices of Consumer Prices. Mixed-effects linear regression models were used to estimate linear and quadratic time trends, with a random intercept and slope fitted to account for variation across countries.Resin potency increased from a mean [95% confidence interval (CI)] of 8.14% THC (6.89, 9.49) in 2006 to 17.22 (15.23, 19.25) in 2016. Resin price increased from 8.21 euros/g (7.54, 8.97) to 12.27 (10.62, 14.16). Resin increased in value, from 11.00 mg THC per euro (8.60, 13.62) to 16.39 (13.68, 19.05). Quadratic time trends for resin potency and value indicated minimal change from 2006 to 2011, followed by marked increases from 2011 to 2016. Herbal cannabis potency increased from 5.00% THC (3.91, 6.23) to 10.22 (9.01, 11.47). Herbal price increased from 7.36 euros/g (6.22, 8.53) to 12.22 (10.59, 14.03). The value of herbal cannabis did not change from 12.65 mg of THC per euro (10.18, 15.34) to 12.72 (10.73, 14.73). All price trends persisted after adjusting for inflation.European cannabis resin and herbal cannabis increased in potency and price from 2006 to 2016. Cannabis resin (but not herbal cannabis) increased in the quantity of Δ9 -tetrahydrocannabinol per euro spent. Marked increases in resin potency and value from 2011 to 2016 are consistent with the emergence of new resin production techniques in European and neighbouring drug markets.

Although research suggests links between emotion regulation strategies and substance use outcomes, little work has examined the relationship between specific strategies (i.e., reappraisal and suppression) and outcomes (i.e., alcohol and cannabis consumption and related problems). To date, no research has examined the association between emotion regulation strategies and protective behavioral strategies used while engaging in substance use. Thus, the current study examined these relations for females and males. Undergraduates (N = 643) completed an online battery of self-report measures. Using structural equation modeling, results indicated improved Emotion Regulation Questionnaire model fit after one item was removed. Reappraisal was negatively associated with alcohol binge frequency and related problems for females, though suppression was negatively related to these outcomes for males. Reappraisal was also negatively associated with cannabis-related problems for males only. Reappraisal was positively associated with all types of protective behavioral strategies use for females, whereas only alcohol-specific serious harm reduction and cannabis protective behavioral strategies were significant for males. Latent variable interactions between reappraisal and protective behavioral strategies were significant for past-month cannabis use and related problems for males and indicated protective behavioral strategies use was more protective against past-month use and cannabis-related problems for those high in reappraisal. Although replication is necessary, these preliminary findings suggest the link between emotion regulation strategies and substance use outcomes among college students is complex and future work may benefit from examining these relations from an emotion regulation flexibility perspective.

To date, research investigating the association between adolescent marijuana use and anxiety is mixed, given differences in how anxiety is measured and the age ranges studied. The research is further limited as many relevant studies have small sample sizes. This investigation examines the association between marijuana use (use in the past 30 days) and anxious mood lability (rapid fluctuation in emotional states) during early adolescence (average age 14.4, spring of 8th grade) through midadolescence (10th grade).Participating adolescents (N = 466; 52.8% female) were from rural and suburban communities and 38% were Hispanic/Latino. Ecological Momentary Assessment (EMA) was used to measure adolescents' anxious mood in real time; the EMAs were collected within 30 days of the adolescent report of their marijuana use.Multilevel models with measurement waves (7 time points) nested in individuals showed that anxious mood lability was significantly higher for adolescents reporting recent marijuana use compared to those reporting no recent marijuana use. Although females were higher than males in anxious mood lability, the association between anxious mood lability and recent marijuana use did not differ by gender. Post hoc analysis showed that the associations between anxious mood lability and recent marijuana use did not differ between assessments conducted pre and post legalization of adult recreational marijuana use.The association between recent marijuana use and anxious mood lability for youth is important for understanding the developmental processes of cannabis use and anxious mood disorders in adolescence and young adulthood.

Recently, multiple compounds have been synthesized that target the allosteric binding site(s) of CB1. These CB1 positive allosteric modulators may capture the benefits of cannabinoid receptor activation without unwanted psychoactive effects, such as sedation. For example, ZCZ011 blocks neuropathic pain, absent the catalepsy, sedation, and hypothermia caused by CB1 orthosteric modulators, including Δ9-tetrahydrocannabinol (THC). The primary goal of the present study was to evaluate the potential of ZCZ011 to attenuate somatic signs of cannabinoid withdrawal in mice. Mice were repeatedly administered THC (10 mg/kg, s.c.) or vehicle, and withdrawal was either precipitated using the CB1 antagonist rimonabant (3 mg/kg, i.p.) or elicited spontaneously via THC abstinence. ZCZ011 (≥10 mg/kg, i.p.) significantly attenuated somatic signs of withdrawal, including head twitches and paw tremors, but had no effect on locomotor activity or conditioned place preference. We next tested the antiulcerogenic properties of CB1 positive allosteric modulation. Mice were fasted for 22 h, administered ZCZ011, and gastric hemorrhages were induced with the nonsteroidal anti-inflammatory drug diclofenac sodium (100 mg/kg, p.o.). ZCZ011 alone had no effect on gastric ulceration, but ZCZ011 (≥10 mg/kg) blocked ulcer formation when combined with a subthreshold MAGL inhibitor (JZL184; 1 mg/kg, i.p.). Thus, CB1 positive allosteric modulation is a novel approach to treat cannabinoid dependence and gastric inflammation.

Introduction: Cannabinoids are well known to have anti-inflammatory effects in mammalians; however, the Cannabis plant also contains other compounds such as terpenoids, whose biological effects have not yet been characterized. The aim of this study was to compare the anti-inflammatory properties of terpenoids with those of cannabidiol (CBD). Materials and Methods: Essential oils prepared from three monoecious nonpsychoactive chemotypes of Cannabis were analyzed for their terpenoid content and subsequently studied pharmacologically for their anti-inflammatory properties in vitro and in vivo. Results:In vitro, the three essential oils rich in terpenoids partly inhibited reactive oxygen intermediate and nitric oxide radical (NO•) production in RAW 264.7 stimulated macrophages. The three terpenoid-rich oils exerted moderate anti-inflammatory activities in an in vivo anti-inflammatory model without affecting tumor necrosis factor alpha (TNFα) serum levels. Conclusions: The different Cannabis chemotypes showed distinct compositions of terpenoids. The terpenoid-rich essential oils exert anti-inflammatory and antinociceptive activities in vitro and in vivo, which vary according to their composition. Their effects seem to act independent of TNFα. None of the essential oils was as effective as purified CBD. In contrast to CBD that exerts prolonged immunosuppression and might be used in chronic inflammation, the terpenoids showed only a transient immunosuppression and might thus be used to relieve acute inflammation.

From centuries ago cannabis has been known as a botanic product with several properties, with medical use in the ancient world. Nowadays, it is recognized as the active component of marijuana, the drug with the highest rates of illicit use and abuse worldwide according to data provided by the World Health Organization. A huge debate has emerged in these past years with the growing interest to employ cannabis-based products with therapeutic purposes, a strategy that has increased in various European countries, Canada and more than half of the states that conform the United States, simultaneously with an important increase of flexibility in laws and regulations regarding the recreational use of this substance, especially in North America. Although valid arguments can exist for each side, the potential therapeutic use of substances that have ethical-legal implications such as the case of cannabis, require the prescribing doctor to be knowledgeable and to always be updated on the subject, a robust doctor-patient relationship and educational campaigns with truthful information that allow for full awareness of risks vs benefits.

With increasing popularity of marijuana, consumers are likely turning to the internet for information regarding medical marijuana. Accuracy of medical marijuana claims is a significant concern because consumers change their medication management based on information from a single website.The purpose of this study was to evaluate the accuracy and quality of medical marijuana claims on popular websites.Commonly used websites containing claims regarding medical marijuana were selected by utilizing three online marketing tools that rank websites based on number of views, number of visitors, and visitor engagement. Once the top ten most popular websites were selected, medical claims regarding marijuana were reviewed for accuracy and quality using evidence-based tools.Seventy-six percent of claims made by websites were inaccurate and were based on low-quality evidence. Of the medical marijuana claims reviewed, 10% of websites made appropriate cause and effect conclusions. Furthermore, approximately 3% of the medical marijuana claims were written by a healthcare professional.The findings show there is misleading and inaccurate information readily available to consumers online.

Nonrandomized response (NRR) models are a new generation of surveys for sensitive issues. This study aims to evaluate the validity of estimates from the crosswise model (as one of the efficient models) through employing different response probabilities of nonsensitive questions.This cross-sectional study was conducted during October and November 2015 among 1777 students of Tabriz University of Medical Sciences. Estimates of monthly alcohol consumption, and at least one instance of illicit drug use and extramarital sex over the last year were determined using direct questioning (DQ) and the Crosswise model (CM). In the last model, the probability of positive response to the nonsensitive questions was determined by using five different methods: uniform distribution (I), Benford's law (II), and estimations based on data from three other studies (III, IV, V).Crosswise estimates of sensitive behaviors with different probabilities of a positive response to nonsensitive questions differed significantly. For example, estimates of history of using illegal opioids at least once in the last year among men varied significantly from 5.0% to 16.1% with different crosswise models based on the probability of being born in Spring using method I (0.250), III (0.287), IV (0.248), and V (0.310). The model based on Benford's law (II) was applied to estimate alcohol and cannabis consumption, and its estimates showed significant discrepancy with results of crosswise models I and V.Estimates from crosswise model is highly sensitive to the response probability of nonsensitive questions. It seems that if this question is not selected carefully, the mentioned models will provide overestimates or underestimates, and the more-is-better hypothesis is not always valid. To achieve valid estimates, the exact probability of a positive response to the nonsensitive question must be known for the studied population.

Recent studies suggest that youth who have a mental health problem are more likely to be NEET-not in education, employment, or training-but findings remain mixed, and evidence from Canada is limited. We examined this association across a range of mental and substance disorders in a representative sample of Canadian youth.Data were from the 2012 Canadian Community Health Survey-Mental Health ( n = 5622; ages 15-29). The survey identified past-year mental (depression, bipolar, generalized anxiety) and substance (alcohol, cannabis, other drugs) disorders from a structured interview and included questions on suicidal ideation. We classified as NEET respondents who were not in school or employed in the past week. Logistic regression models tested the associations between mental and substance disorders and NEET status, adjusted for sociodemographic, health, and geographic variables.About 10% of youth were NEET. Being NEET was associated with past-year depression (odds ratio [OR] = 1.67; 95% confidence interval [CI], 1.06 to 2.63); bipolar (OR = 2.31; 95% CI, 0.98 to 5.45), generalized anxiety (OR = 2.65; 95% CI, 1.37 to 5.12), and drug use (OR = 3.22; 95% CI, 1.33 to 7.76) disorders; and suicidal ideation (OR = 1.75; 95% CI, 0.99 to 3.09) but was not associated with alcohol (OR = 1.03; 95% CI, 0.63 to 1.69) or cannabis (OR = 0.97; 95% CI, 0.47 to 2.00) disorders.Poor mental health was associated with being NEET in Canadian youth. Efforts targeting NEET should include provisions for mental health. Moreover, youth mental health initiatives should consider educational and employment outcomes. Further longitudinal and intervention studies are warranted.

While Δ9-tetrahydrocannabinol (THC) has been widely studied in the realm of developmental and reproductive toxicology, few studies have investigated potential toxicities from a second widely used cannabis constituent, cannabidiol (CBD). CBD is popularized for its therapeutic potential for reducing seizure frequencies in epilepsy. This study investigated developmental origins of health and disease (DOHaD) via multigenerational gene expression patterns, behavior phenotypes, and reproductive fitness of a subsequent F1 following an F0 developmental exposure of zebrafish (Danio rerio) to THC (0.024, 0.12, 0.6 mg/L; 0.08, 0.4, 2 μM) or CBD (0.006, 0.03, 0.15 mg/L; 0.02, 0.1, 0.5 μM). Embryonic exposure at these concentrations did not cause notable morphological abnormalities in either F0 or F1 generations. However, during key developmental stages (14, 24, 48, 72, and 96 h post fertilization) THC and CBD caused differential expression of c-fos, brain-derived neurotrophic factor (bdnf), and deleted-in-azoospermia like (dazl), while in F1 larvae only CBD differentially expressed dazl. Larval photomotor behavior was reduced (F0) or increased (F1) by THC exposure, while CBD had no effect on F0 larvae, but decreased activity in the unexposed F1 larvae. These results support our hypothesis of cannabinoid-related developmental neurotoxicity. As adults, F0 fecundity was reduced, but it was not in F1 adults. Conversely, in the adult open field test there were no significant effects in F0 fish, but a significant reduction in the time in periphery was seen in F1 fish from the highest THC exposure group. The results highlight the need to consider long-term ramifications of early-life exposure to cannabinoids.

Marijuana has a complicated legal, social, and economic history in the United States, as well as an uncertain future. Marijuana has been consistently tied to racial minority groups since its arrival in the United States in the 1900s, and former Attorney General Jeff Sessions further propagated that notion. AG Sessions even recently wrote a memo that directly contradicted Obama-era policy, demonstrating that the current legal status of marijuana in both state and federal government is currently up for debate. While several states have legalized marijuana for medical or even recreational purposes, federal law still categorizes cannabis as a drug with no currently accepted medical use and a high potential for abuse. The comparison between marijuana, opioids, and ketamine in this article demonstrates that marijuana has been unnecessarily withheld and stigmatized by the federal government. Also reviewed is the impact of stringent marijuana-based legal policies upon the racial makeup of prison populations. The implications of current policy upon potential and future research are also discussed, with the determination that current policy has stymied research and prevented a more accurate determination of the risks and benefits of medical marijuana.

Homeless youth in the United States have high rates of substance use. Existing research has identified social network composition and street-associated stressors as contributing factors. Incarceration is a highly prevalent stressor for homeless youth. Its effect on youth's social network composition and substance use, however, has been neglected.This study investigated the direct and indirect associations between incarceration history and substance use (through social networks) among homeless youth in Los Angeles, California.A sample of 1047 homeless youths were recruited between 2011 and 2013. Computerized self-administrated surveys and social network interviews were conducted to collect youth's sociodemographic characteristics, incarceration history, social network composition, and substance use. Bootstrapping was used to identify the direct and indirect associations between youth's incarceration history and substance use.Incarceration history was positively associated with youth's cannabis, methamphetamine, and injection drug use. The percentage of cannabis-using peers partially mediated the associations between incarceration history and youth's cannabis, cocaine, and heroin use. The percentage of methamphetamine-using peers partially mediated the associations between incarceration history and youth's methamphetamine, cocaine, and injection drug use. The percentage of heroin-using peers partially mediated the association between incarceration history and youth's heroin use. Moreover, the percentage of peers who inject drugs partially mediated the associations between incarceration history and youth's methamphetamine, heroin, and injection drug use.Incarceration history should be taken to a more central place in future research and practice with homeless youth in the United States.

A series of chemical and biochemical parameters of edible hemp resources (seeds, oil, and flour) from the monoecious EU registered hemp genotype Fedora, was determined, including fatty acid profile, phytosterol composition, total phenolics, antioxidant activity, macro- and micro-elements. The fatty acid ω-3/ω-6 approached the nutritionally optimal 3/1 ratio. β-sitosterol and other phytosterols sterols dominated the unsaponifiable fraction. Hemp seeds, flour, and oil contained 767 ± 41, 744 ± 29, and 21 ± 5 mg GAE kg-1 total polyphenols, respectively. The antioxidant potential of Fedora flour and seeds, evaluated through the DPPH (2,2-Diphenyl-1-picrylhydrazyl) assay, was higher than that of oil. K and Mg were the most abundant macro-elements, particularly in flour, while the concentration of trace elements was Fe > Cu > Ni > Mn. The presence of an array of bioactive compound candidate Fedora products as health-promoting food matrices. The ATR-FTIR spectra of hemp-derived products indicated the proximate composition of macro-nutrients.

The current pilot study probed the time course of attentional bias to cannabis-related cues among individuals with cannabis use disorders (CUDs) compared with healthy controls. Forty participants (individuals with CUDs, n = 20, Mage = 26.2 and healthy controls, n = 20, Mage = 28) completed a modified visual attention task in which they made decisions about the orientation of a target line while ignoring temporally flanking lines and cannabis-related, positive-, negative-, and neutral-images as behavioral responses and event-related potentials (ERPs) were recorded. To examine the time course of attentional bias, we analyzed ERP responses separately to targets and distractors from 125 ms to 620 ms after stimulus onset. Results showed that, compared with healthy controls, cannabis users demonstrated greater selective attention failure (i.e., had more difficulties ignoring distractor stimuli) when making decisions in the presence of cannabis cues. Likewise, cannabis smokers demonstrated relatively larger differences in accuracy (i.e., committed more errors in target decisions) between trials involving cannabis cues versus neutral cues. ERP data revealed that the N1 component (125-200 ms after stimulus onset) to flankers preceding cannabis cues peaked relatively earlier and was of larger amplitude in cannabis users, suggesting an early perceptual bias toward the cannabis cues. Findings suggest that individuals with CUDs have poorer selective attention, impaired inhibitory control, and early attentional biases toward cannabis uses compared with healthy nonusers. The augmented early perceptual response suggests an involuntary orienting of attention toward cannabis cues. Implications for future research and intervention development for individuals with CUD are discussed. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

The aim of this survey was to assess the stress in fishermen by analysing its relationship with sociodemographic and professional characteristics, by evaluating work stressors, and by estimating psychosomatic symptoms.This cross-sectional survey involved representative sample of 828 artisanal and coastal fishermen. All participants were men and had a regular activity for at least 2 years. We used an individual questionnaire inspired by those of the National Institute for Research and Security of France and of the Karasek's Job Content Questionnaire.The prevalence of self-reported stress was 53.9%. The average age was 36.7 ± 8.7 years, it was higher among stressed than non-stressed. The prevalence of stress was higher in subjects with dependents (69.1%) versus 30.9% without dependents, and among those living alone (61%) versus 47.5% among those living in couple. The prevalence of harmful habits was 68.5% for tobacco smoking or snuff, 36.8% for cannabis smoking, 35.4% for alcohol consumption, 8.6% for other psychotropic substances and medications, and 21.4% for antalgic drugs. These toxic habits were significantly higher in stressed individuals. Thirty-three point seven per cent had self-reported chronic pathologies (40.5% among stressed vs. 25.7% non-stressed). Thirty-four per cent were overweight (38.3% among stressed vs. 28.8% non-stressed), and 14% obese (19.3% among stressed vs. 7.6% non-stressed). The average daily working hours were 11.2 h (12.8 h among stressed subjects vs. 10.5 h non-stressed). Psychological demand was higher in stressed subjects, while decisional latitude and social support were lower. Psychosomatic symptoms were higher among stressed than non-stressed. The main suggestions of the fishermen were to improve income, social welfare, health insurance, safety on board, quality of lifestyle, sport and leisure activities, information and awareness campaigns of occupational stress, and fight against addictive behaviours.Fishermen were at a high risk of chronic stress with its health consequences. Health promotion and education initiatives should be conducted to raise fishermen's awareness of the dangers of occupational stressors.

At Risk Mental State (ARMS) clinics are specialised mental health services for young, help-seeking people, thought to be at ultra-high risk of developing psychosis. Their stated purpose is to reduce transitions from the ARMS state to clinical psychotic disorder. Reports of ARMS clinics provide 'evidence-based recommendations' or 'guidance' for the treatment of such individuals, and claim that such clinics prevent the development of psychosis. However, we note that in an area with a very well-developed ARMS clinic (South London), only a very small proportion (4%) of patients with first episode psychosis had previously been seen at this clinic with symptoms of the ARMS. We conclude that the task of reaching sufficient people to make a major contribution to the prevention of psychosis is beyond the power of ARMS clinics. Following the preventative approaches used for many medical disorders (e.g. lung cancer, coronary artery disease), we consider that a more effective way of preventing psychosis will be to adopt a public health approach; this should attempt to decrease exposure to environmental factors such as cannabis use which are known to increase risk of the disorder.

With limited Canadian research on predictors of drug use during pregnancy, the primary objective was to assess the relative effects of socioeconomic, demographic, and mental health risk factors associated with drug use during pregnancy. Predictors of an Apgar score <  7 and fetal macrosomia were examined as secondary outcomes.This retrospective cohort study consisted of 25,734 pregnant women from Southwestern Ontario. Data were prospectively obtained from perinatal and neonatal databases at a tertiary hospital in London, Ontario. Using a Geographic Information System, neighborhood-level socioeconomic variables were obtained by mapping maternal postal codes. Separate logistic regressions were computed for all outcome variables.The rates of alcohol, tobacco, and cannabis use during pregnancy were 1.9%, 16.2%, and 2.3%, respectively. The mean maternal age was 29.4±5.4 years. Maternal age was inversely associated with alcohol, tobacco and cannabis use, whereas lone-parent household, depression, and anxiety increased the odds of substance use. Depression was the top risk factor of all three substances. Compared to women who were not depressed during pregnancy, women who were depressed were 2.15 times more likely to use alcohol (95% CI: 1.60, 2.90), 1.70 times more likely to smoke tobacco (95% CI: 1.48, 1.95), and 2.56 times more likely to use cannabis (95% CI: 1.95, 3.35). Adverse birth outcomes were also associated with overweight and obesity, gestational diabetes and insulin-dependent diabetes.Maternal depression is the primary risk factor of drug use during pregnancy. Policy interventions that target at-risk women are important considerations to improve maternal mental health.

The endocannabinoids system (ECS) has garnered considerable interest as a potential therapeutic target in various carcinomas and cancer-related conditions alongside neurodegenerative diseases. Cannabinoids are implemented in several physiological processes such as appetite stimulation, energy balance, pain modulation and the control of chemotherapy-induced nausea and vomiting (CINV). However, pharmacokinetics and pharmacodynamics interactions could be perceived in drug combinations, so in this short review we tried to shed light on the potential drug interactions of medicinal cannabis. Hitherto, few data have been provided to the healthcare practitioners about the drug⁻drug interactions of cannabinoids with other prescription medications. In general, cannabinoids are usually well tolerated, but bidirectional effects may be expected with concomitant administered agents via affected membrane transporters (Glycoprotein p, breast cancer resistance proteins, and multidrug resistance proteins) and metabolizing enzymes (Cytochrome P450 and UDP-glucuronosyltransferases). Caution should be undertaken to closely monitor the responses of cannabis users with certain drugs to guard their safety, especially for the elderly and people with chronic diseases or kidney and liver conditions.

Nurses are important agents in public health, which includes being active in tobacco control. Studies show that nurses who smoke are less inclined to offer smoking cessation aid. Nursing students, as the future labor force of nursing, are one of the key groups to monitor.To identify the prevalence and determinants of use of several tobacco products, e-cigarettes, and cannabis among nursing students in Catalonia.Cross-sectional multicenter study.15 university nursing schools in Catalonia (Spain) in 2015-2016.Nursing students attending class at the day of the survey.An anonymous, self-administered questionnaire based on the Global Health Professional Survey was designed. The questions included information on consumption of several tobacco products (manufactured cigarettes, roll your own cigarettes, etc.), e-cigarettes, and cannabis. We estimated the prevalence of use (%) and computed multilevel logistic regressions models, at two levels, to calculate the odds ratios (OR) and their corresponding 95% confidence intervals (CI), adjusting for several individual sociodemographic variables and the nursing school as a grouping variable.4381 students participated in the study (57.2% of Nursing students in Catalonia at the time of the survey). 29.7% (95%CI: 27.2-32.2) were smokers (18.4% daily and 11.3% occasionally). 66.4% smoked manufactured cigarettes, 47.0% roll your own cigarettes, 10.0% waterpipe, and 0.4% e-cigarettes. The main predictors of smoking were: being ≥25 years (OR = 2.57, 95%CI: 2.03-3.26) and belonging to other Spanish regions (OR = 1.82, 95%CI: 1.30-2.54). 71.5% had low nicotine dependence as defined by the Heavy Smoking Index. Among 11.5% (95%CI: 10.6-12.4) of students used cannabis (daily or occasionally), and men presented higher odds of use (OR = 2.81, 95%CI: 2.11-3.73) than women.Tobacco and cannabis use is high among nursing students. It is necessary to carry out early tobacco and cannabis cessation programs among young nursing students.

Cannabis use increases the risk of developing psychosis, and subjects with psychosis are more likely to use cannabis. However, studies on the influence of cannabis on psychotic dimensions, response to treatment, and functional outcomes showed conflicting results. Such heterogeneity may be due the inclusion of patients who were already under treatment, and lack of specificity in evaluations. We investigated whether cannabis use yields distinct symptom profiles and functionality in a cohort of antipsychotic-naïve patients at first episode of psychosis (FEP).This research is part of a prospective cohort study performed in Sao Paulo, Brazil. The baseline assessment was completed by 175 individuals, and 99 of them were reassessed in a ten-week follow up. We investigated the relationship between cannabis exposure variables (acute use, lifetime use and age at first use) and outcomes: symptom dimensions and functioning.Individuals who reported acute use of cannabis had higher excitement symptoms at baseline, higher excitement and positive response rates, but no significant differences at follow-up. Additionally, more days of cannabis use in the last month predicted worse functionality and clinical impression at baseline but not at follow-up.The acute use of cannabis influenced the clinical presentation at our FEP baseline assessment, but did not to influence symptoms or functional outcomes at 10-week follow-up. Additionally, acute cannabis users had a better response for excitement and positive symptoms. Higher excitement symptoms at presentation of FEP should raise concerns of possible acute use of cannabis. Longer follow-up times may elucidate whether the effects on functionality would be more evident later in disease development.

The aim of this study was to explore the pharmacokinetics of the two main active compounds (THC and CBD) contained in the cannabis oil extract Bedrocan® in fasting and fed dogs. Bedrocan® (20% delta-9-tetrahydrocannabinol [THC] and 0.5% cannabidiol [CBD]) was administered at 1.5 and 0.037 mg/kg THC and CBD, respectively in fasted and fed dogs according to a 2 × 2 cross over study design. The quantification of the two active ingredients was performed by LC/MS. No detectable concentrations of CDB were found at any collection time. THC was quantifiable from 0.5 to 10 h, although there was large inter-subject variability. Fed dogs showed a longer absorption phase (Tmax 5 vs 1.25 h) and lower maximal blood concentration (7.1 vs 24 ng/mL) compared with the fasted group. A larger AUC was found in the fasted group; the relative oral bioavailability in fed animals was 48.22%.

Persistent post-surgical pain and associated disability are common after a traumatic fracture repair. Preliminary evidence suggests that patients' beliefs and perceptions may influence their prognosis.We used data from the Fluid Lavage of Open Wounds trial to determine, in 1560 open fracture patients undergoing surgical repair, the association between Somatic PreOccupation and Coping (captured by the SPOC questionnaire) and recovery at 1 yr.Of the 1218 open fracture patients with complete data available for analysis, 813 (66.7%) reported moderate to extreme pain at 1 yr. The addition of SPOC scores to an adjusted regression model to predict persistent pain improved the concordance statistic from 0.66 to 0.74, and found the greatest risk was associated with high (≥74) SPOC scores [odds ratio: 5.63; 99% confidence interval (CI): 3.59-8.84; absolute risk increase 40.6%; 99% CI: 30.8%, 48.6%]. Thirty-eight per cent (484 of 1277) reported moderate to extreme pain interference at 1 yr. The addition of SPOC scores to an adjusted regression model to predict pain interference improved the concordance statistic from 0.66 to 0.75, and the greatest risk was associated with high SPOC scores (odds ratio: 6.06; 99% CI: 3.97-9.25; absolute risk increase: 18.3%; 95% CI: 11.7%, 26.7%). In our adjusted multivariable regression models, SPOC scores at 6 weeks post-surgery accounted for 10% of the variation in short form-12 physical component summary scores and 14% of short form-12 mental component summary scores at 1 yr.Amongst patients undergoing surgical repair of open extremity fractures, high SPOC questionnaire scores at 6 weeks post-surgery were predictive of persistent pain, reduced quality of life, and pain interference at 1 yr.NCT00788398.

African Americans have the most severe burden of human immunodeficiency virus (HIV) of all racial/ethnic groups in the United States. Also, HIV continues to be a serious threat to the health of the Hispanic/Latino community. For prevention purposes, the present study examined the relationship of both cannabis use and self-control with HIV risk behaviors in a sample of African American and Puerto Rican female adolescents, young adults, and adults. Among the total of 343 female participants, half were African American and the other half were Puerto Rican. Logistic regression analyses were used to examine earlier cannabis use as well as self-control and later HIV risk behaviors. High frequency of cannabis use and high self-control measured at ages 19 to 29 were positively and negatively related to having sexual intercourse with someone they just met at ages 32 to 39. Prevention programs should incorporate the role of cannabis use and low self-control as related to HIV risk behaviors. Our results may have particular utility for designing interventions focused on not only cannabis use (a risk factor) but also self-control (a protective factor) as related to HIV sexual risk behaviors.

There is increasing interest in the effect of legalization (particularly recreational legalization) of cannabis on prevalence of use and related problems. However, there is no consensus about the impact of policy change on cannabis use, particularly among adolescents. Legalization may increase adolescent use through mediating factors such as perceived risk and normative beliefs regarding the use of cannabis. Washington State enacted Initiative 502 on December 2012, which legalized and taxed recreational cannabis for adults aged ⩾21 years. This paper used data from a randomized, controlled intervention trial for cannabis-using adolescents that was recruiting participants in Seattle before and after the policy change to evaluate the following goals: assess differences in substance use, problems, and symptomatology pre- and post-policy change; evaluate several proposed risk factors that may be associated with such differences; and describe participants' understanding of the law and how this understanding may relate to rates of use. Analyses revealed no significant differences pre- to post-policy in rate of substance use. However, there were significant post-policy increases in problems and use disorder symptoms. Despite these differences, there were no significant increases in norms, attitudes, or perceptions of risk. Participants were able to answer most questions regarding policy changes correctly, indicating a good understanding of the policy. Results provided no evidence that policy change influenced heavy-using adolescents' rates of use nor the proposed risk factors associated with problematic use patterns.

In Canada, substance use is one of the key predisposing factors that may lead to risky sexual behaviors among post-secondary students. There is considerable economic burden and significant public health concern posed by substance use and sexually transmitted infections (STIs). The purpose of this study was to examine the prevalence of substance use preferences (alcohol, cannabis, and other drugs) and its association with STIs among Canadian post-secondary students.This is a cross-sectional study using data from the National College Health Assessment II, Spring 2016 survey conducted by the American College Health Association. There were 31,642 sexually active participants, representing 41 post-secondary institutions in Canada. Descriptive analysis and logistic regression were conducted to estimate the effect of substance use preferences on STIs.This study found that participants reported being current users of alcohol (80%), cannabis (23%), and other drugs (8%). Additionally, 3.96% of the participants self-reported being diagnosed or treated for an STI in the last 12 months. Multivariate logistic analysis revealed current cannabis use to be significantly associated with self-reported STIs (aOR, 1.34; 95% CI, 1.12-1.6). There was a significant association between current drug use and STIs among male (aOR, 3.04; 95% CI, 2.27-4.06) and female participants (aOR, 1.87; 95% CI, 1.52-2.30). Having multiple sexual partners, a history of sexual assault, being homosexual, Black, and >21 years old were also found to have a significant association with self-reported STIs (P-value <0.001).In this study, significant associations were found between cannabis and other drug use and STIs among post-secondary students in Canada. The results of this study can help inform institutions of higher learning and public health professionals in the design, implementation, and evaluation of substance use and STI policies and effective school-based health programming.

Examine the risk of preterm birth (PTB, < 37 weeks) and early term birth (37-38 weeks) for women with reported drug abuse/dependence.The population was drawn from singleton livebirths in California from 2007 to 2012. Drug abuse/dependence was determined from maternal diagnostic codes (opioid, cocaine, cannabis, amphetamine, other, or polysubstance). Relative risks, adjusted for maternal factors were calculated for PTB and early term birth.Of the 2,890,555 women in the sample, 1.7% (n = 48,133) had a diagnostic code for drug abuse/dependence. The percentage of PTBs varied from 11.6% (cannabis) to 24.3% (cocaine), compared with 6.7% of women without reported drug abuse/dependence.Women with reported drug abuse/dependence during pregnancy were at increased risk of having a PTB and all but those using cannabis were at risk of having an early term birth. Women using cocaine and polysubstance were at the highest risk of birth < 32 weeks.

Lifestyle risk factors, such as drinking or unhealthy diet, can expotentiate detrimental health effects. Therefore, it is important to investigate multiple lifestyle risk factors instead of single ones. The study aims at: (1) identifying patterns of lifestyle risk factors within the adult general population in Germany and (2) examining associations between the extracted patterns and external factors.Cross-sectional study.General German adult population (aged 18-64 years).Participants of the 2015 Epidemiological Survey of Substance Abuse (n=9204).Lifestyle risk factors (daily smoking, at-risk alcohol consumption, unhealthy diet, low physical activity, weekly use of pharmaceuticals, as well as consumption of cannabis and other illicit drugs).A latent class analysis was applied to identify patterns of lifestyle risk factors, and a multinomial logistic regression was carried out to examine associations between the extracted classes and external factors. A total of four classes were extracted which can be described as healthy lifestyle (58.5%), drinking lifestyle (24.4%), smoking lifestyle (15.4%) and a cumulate risk factors lifestyle (1.7%). Individuals who were male, at younger age and single as well as individuals with various mental health problems were more likely to show multiple lifestyle risk factors.Healthcare professionals should be aware of correlations between different lifestyle risk factors as well as between lifestyle risk groups and mental health. Health promotion strategies should further focus especially on younger and single men.

Cannabis is the most prevalent illicit drug used by adolescents worldwide. Over the past 40 years, changes in cannabis potency through rising concentrations of Δ-9-tetrahydrocannabiol (THC), decreases in cannabidiol, or both, have occurred. Epidemiological and experimental evidence demonstrates that cannabis with high THC concentrations and negligible cannabidiol concentrations is associated with an increased risk of psychotic outcomes, an effect on spatial working memory and prose recall, and increased reports of the severity of cannabis dependence. However, many studies have failed to address cannabis use in adolescence, the peak age at which individuals typically try cannabis and probably the most vulnerable age to experience its harmful effects. In this Review, we highlight the influence that changing cannabis products have on adolescent health and the implications they carry for policy and prevention measures as legal cannabis markets continue to emerge worldwide.

To determine if higher potency cannabis is associated with earlier progression to regular cannabis use, daily cannabis use, and cannabis use disorder symptom onset.Data sources were the Michigan Longitudinal Study, an ongoing prospective, high-risk family study investigating the course and predictors for substance use disorders among youth beginning prior to school entry and time-parallel national average trends in delta-9-tetrahydrocannabinol (i.e., psychoactive compound in cannabis). The national average trends in delta-9-tetrahydrocannabinol were used to estimate potency level for the individual. Only cannabis users were included in analyses (n = 527).Cox regression showed an increased risk of progression from cannabis initiation to cannabis use disorder symptom onset by 1.41 times (p < .001) for each unit increase in national average delta-9-tetrahydrocannabinol as compared to those not endorsing CUD symptom onset, adjusting for sex, regular use, and cohort effects. Accounting for regular use, individuals initiating cannabis at national average 4.9% delta-9-tetrahydrocannabinol were at 1.88 times (p = .012) higher risk for cannabis use disorder symptom onset within one year compared to those who did not endorse CUD symptom onset, while those initiating cannabis at national average 12.3% delta-9-tetrahydrocannabinol were at 4.85 times (p = .012) higher risk within one year.This study provides prospective evidence suggesting higher potency cannabis, on average in the U.S., increases risk for onset of first cannabis use disorder symptom. Development of guidelines regarding cannabis potency is critical for reducing the costs associated with negative health outcomes.

A small body of work has started developing cannabis use "typologies" for use in treatment and prevention. Two potentially relevant dimensions for classifying cannabis use typologies are medical versus recreational cannabis use and the co-use of cannabis and alcohol. Here we compare alcohol use and related problems between cannabis users with and without medical cannabis recommendations.Data come from a larger general population study in Washington State conducted between January 2014 and October 2016. All participants in the analytic sample (n = 991) reported using both alcohol and cannabis in the past 12 months. The primary exposure was having a medical recommendation for cannabis. Outcomes were past-30-day drinking (drinks/day, frequency of 5+ drinks, and maximum number of drinks in a day) and past-12-month Alcohol Use Disorders Identification Test (AUDIT) scores.Compared with those without medical cannabis recommendations, cannabis users with medical cannabis recommendations had 0.59 times fewer drinks/day, 0.44 times fewer occasions drinking 5+, and 0.78 times the average maximum number of drinks in one day (all ps < .05). Those with a recommendation also had 0.87 times lower AUDIT total scores (p < .05) and 0.57 times lower AUDIT problem scores (p < .01).Cannabis users with medical cannabis recommendations drink less and have fewer alcohol-related problems than those without recommendations, even after adjusting for health status. Future studies should examine nonhealth reasons regarding how medical and nonmedical users use cannabis differently.

Co-use of cannabis and alcohol is associated with increased drinking and other negative consequences relative to use of alcohol alone. One potential explanation for these differences is overvaluation of alcohol (e.g., alcohol demand) among co-users, similar to established overvaluation of alcohol among tobacco and alcohol co-users. This study examined differences in alcohol demand between an alcohol and cannabis co-user group and an alcohol-only group.A large sample of adult drinkers (n = 1,643, 54% female) was recruited through an online crowdsourcing site (Amazon Mechanical Turk). Of the full sample, 476 participants reported weekly or greater cannabis use in the past 6 months (co-user group); 888 reported never using cannabis in the past 6 months (alcohol-only group). Assessments included a validated alcohol purchase task and self-report measures of alcohol and cannabis use.Co-users reported significantly higher alcohol consumption across the elastic portion of the alcohol demand curve (i.e., $1.50-$9.00/drink). Analyses of covariance controlling for alcohol use and demographics revealed significantly higher breakpoint (p = .025) and Omax (p = .002) and significantly lower elasticity (p < .003) in the co-user group. Intensity and Pmax did not significantly differ between groups.Co-users of cannabis and alcohol overvalue alcohol compared with individuals who drink alcohol but do not use cannabis. This study is generally consistent with prior studies on alcohol and tobacco co-users, providing converging evidence that polysubstance use is associated with overvaluation of alcohol. These findings have important implications for treatment and prevention, particularly in the context of changes in cannabis legalization.

Several epidemiological studies have reported that veterans and nonveterans have comparable substance use disorder (SUD) prevalence and SUD treatment rates for SUD and treatments of several types. No studies have compared functioning among veterans with SUD to veterans without SUD or to nonveterans.We investigated the prevalence of past-year and lifetime SUD (based on criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition), overall and by substance, and estimated the association with physical and mental health functioning and treatment utilization and need among veterans and nonveterans in a nationally representative sample.Predicted prevalence of any past-year SUD, with and without tobacco use disorder (TUD), among veterans was 32.9% and 17.1%, and prevalence of any lifetime SUD, with and without TUD, was 52.5 and 38.7%, respectively. Veterans had higher prevalence of past-year and lifetime SUD for some substances (e.g., tobacco, alcohol) but not others (e.g., cannabis, opioid). Lower physical and mental health functioning was found among veterans, relative to nonveterans, and participants with SUD, relative to those without SUD, and veterans with SUD reported the lowest functioning across all domains. More veterans than nonveterans received any SUD treatment and SUD treatment in specific domains (e.g., self-help). About 70% of veterans with past-year SUD did not receive treatment, but only 5.4% reported needing and not receiving treatment.Relative to nonveterans, veterans have higher prevalence of past-year TUD and lifetime alcohol use disorder or TUD and lower physical or mental health functioning. A minority of veterans receive SUD treatment, and few report unmet need for treatment.

Changes in gray matter volume and thickness are associated with adolescent alcohol and cannabis use, but the impact of these substances on surface area remains unclear. The present study expands on previous findings to examine the impact of alcohol and cannabis on surface area before and after use initiation.Scans for 69 demographically similar youth were obtained at baseline (ages 12-14 years; before substance use) and at 6-year follow-up (ages 17-21 years). Participants were classified into three groups based on substance use: alcohol use initiators (ALC, n = 23), alcohol and cannabis use initiators (ALC+CU, n = 23), and individuals with minimal substance use (<3 lifetime alcohol and 0 marijuana use episodes; CON, n = 23). For each hemisphere, group differences in surface area across time (pre- and post-substance use initiation) and significant group-by-time interactions were examined individually for 34 cortical regions using repeated measures analysis of covariance. A vertex-wise analysis assessed group differences in surface area percent change.A significant group-by-time interaction was found in three regions, bilateral medial orbitofrontal cortices and right insula. Although all regions showed decreases in surface area over time (ps < .05), a more substantial decrease was identified in the ALC group. Of note, the right medial orbitofrontal cortex survived the conservative vertex-wise analyses (p < .001), as a more substantial decrease was found in the ALC compared to the ALC+CU group in this region.Surface area in the medial orbitofrontal cortex may be a useful intermediate phenotype for exploring the mechanisms underlying the effects of substance use on brain development.

A flowering plant of variegated ingredients and psychoactive qualities, Cannabis has long been used for medicinal and recreational purposes. Regulatory approvals have been gained across a broad range of palliative and therapeutic indications, and in some cases, included in standard treatment guidelines. Areas covered: The use of Cannabis and cannabinoid-based-medicines in oncology is summarized in this article. Cannabinoids are classified according to natural and synthetic subtypes and their mechanisms of action expounded. The variability of available products is discussed in the clinical context and data regarding chemotherapy-induced nausea and vomiting, cancer-related pain, anorexia, insomnia, and anxiety are presented. Moreover, immunological and antineoplastic effects in preclinical and clinical trials are addressed. Concepts such as synergism or opposition with conventional treatment modalities, the sequence of administration and dosage, molecular cross-talk and malignancy-cannabinoid congruence, are explored. Finally, side-effects, limitations in trial design and legislation barriers are related. Expert opinion: Sufficient evidence supports the use of Cannabis for palliative indications in oncology; however, patients should be carefully selected, guided and followed. Promising research suggests the potent antineoplastic activity, but more data must be accrued before conclusions can be drawn.

Substance use disorder (SUD) during pregnancy requires efficacious interventions based on understanding the ebb and flow of risk and protective factors for substance use across time. To assess how these fluctuations are associated temporally with substance use, we used ecological momentary assessment (EMA) to evaluate substance use risk (posttraumatic stress disorder [PTSD] symptoms) and protective (prenatal fetal bonding) factors and their associations with prenatal substance use recorded in real time.Pregnant women in SUD treatment (N = 33) with prior trauma exposure received smartphones with an EMA application that queried them thrice daily for 28 days about PTSD symptoms, prenatal bonding, and substance use.Nearly all (N = 32) provided EMA data resulting in 2049 EMA reports (74% compliance). Most participants reported tobacco (72%), alcohol (22%), heroin (41%), and/or other illicit drug (6%-31%) use at least once via EMA. There were moderate associations (average β = 0.23) between greater daily peak PTSD symptoms and substance use with significant effects on illicit drug (β = 0.37), cannabis (β = 0.35) and cigarette use (β = 0.24). Prenatal bonding subscales were modestly associated with substance use, with daily intensity of attachment low point associated with lower heroin (β=-0.34), but higher alcohol (β = 0.24) use. Quality of attachment low point was associated with higher cigarette use (β = 0.06).Despite the SUD severity and social instability of this sample, we observed high rates of compliance. We found preliminary support suggesting daily PTSD symptoms as a risk factor and less consistent support for prenatal bonding as a protective factor for prenatal substance use.

The current study explores the therapeutic potential of Cannabidiol (CBD), a compound in the Cannabis plant, using both sexes of 2 "depressive-like" genetic models, Wistar Kyoto (WKY) and Flinders Sensitive Line (FSL) rats. Rats ingested CBD (30 mg/kg) orally. In the saccharin preference test, following a previous report of a pro-hedonic effect of CBD in male WKY, we now found similar results in female WKY. CBD also decreased immobility in the forced swim test in males (both strains) and in female WKY. These findings suggest a role for CBD in treating mental disorders with prominent symptoms of helplessness and anhedonia.

Pancreatitis is an increasingly common clinical condition that causes significant morbidity and mortality. Cannabis use causes conflicting effects on pancreatitis development. We conducted a larger and more detailed assessment of the impact of cannabis use on pancreatitis.We analyzed data from 2012 to 2014 of the Healthcare Cost and Utilization Project-Nationwide Inpatient Sample discharge records of patients 18 years and older. We used the International Classification of Disease, Ninth Edition codes, to identify 3 populations: those with gallstones (379,125); abusive alcohol drinkers (762,356); and non-alcohol-non-gallstones users (15,255,464). Each study population was matched for cannabis use record by age, race, and gender, to records without cannabis use. The estimation of the adjusted odds ratio (aOR) of having acute and chronic pancreatitis (AP and CP) made use of conditional logistic models.Concomitant cannabis and abusive alcohol use were associated with reduced incidence of AP and CP (aOR: 0.50 [0.48 to 0.53] and 0.77 [0.71 to 0.84]). Strikingly, for individuals with gallstones, additional cannabis use did not impact the incidence of AP or CP. Among non-alcohol-non-gallstones users, cannabis use was associated with increased incidence of CP, but not AP (1.28 [1.14 to 1.44] and 0.93 [0.86 to 1.01]).Our findings suggest a reduced incidence of only alcohol-associated pancreatitis with cannabis use.

SummaryHumans have always used mind-altering drugs. However, in 1961 the United Nations approved the Single Convention, under which the production, sale or possession of a number of drugs, including heroin, cocaine, ecstasy and cannabis, became illegal. The prohibitionist regime was then introduced by most countries around the world and has substantially remained in place ever since. Some countries, particularly those in Latin America, have never criminalised the use of cannabis. A small number of countries have introduced more liberal policies. This article examines the evidence of the consequences of policy liberalisation and argues that there is now a clear case for every country to examine its drug policies and to introduce evidence-based policies with a public health focus.Declaration of interestNone.

Research has shown that a history of childhood adversities is common in patients with psychiatric disorders but few studies have investigated links between specific types of adversity and specific psychiatric disorders.We investigated the frequency of early childhood adversities in a sample consisting of 91 patients with diagnosis of schizophrenic spectrum disorders (SSD), 74 patients with bipolar disorder (BD), 83 patients with major depressive disorder (MDD) and 85 healthy controls and sought to identify adverse early childhood life events that predict the development of major psychiatric disorders. The Childhood Experiences of Care and Abuse questionnaire was used to collect data on traumatic experiences occurring before the age of 17 years and comprehensive demographic data were also collected. The data were analyzed with chi-squared tests, t-tests, post-hoc and logistic regression.Maternal absence/loss and economic difficulties in the early life were more prevalent in the BD group than other groups. Escape from home, cannabis abuse, psychological abuse, physical abuse and loneliness were more frequent in the SSD group than in other groups. Paternal absence, neglect of core needs, serious familial tension and absence of adult and peer confidants were all less common in the HC group than in the other groups. The regression model confirmed that different types of adversities play a crucial role in the development of the three investigated disorders.Our results support that SSD, BD and MDD are associated to different childhood adversities. This suggests that psychosocial interventions that reduce the incidence of these early life adversities might reduce the incidence of severe and disabling psychiatric disorders.

Marijuana is the most commonly used psychoactive drug in the USA. A 35-year-old man with a medical history of marijuana abuse is admitted to the hospital due to crushing substernal chest pain. ECG shows evolving ST-segment elevation with a rise in cardiac enzymes, consistent with ST-elevation myocardial infarction. A urine toxicology screen is positive for cannabis and negative for cocaine and other stimulant drugs. An emergent cardiac catheterisation reveals no evidence of coronary artery disease or thrombosis. A diagnosis of coronary vasospasm is strongly considered, and the patient is started on calcium channel blocker, with a resolution of symptoms and ECG changes. Marijuana-induced coronary spasm causing myocardial infarction has rarely been reported. Marijuana is becoming a social norm in adolescents and there remains a misconception that it is harmless and even beneficial. Increasing drug abuse remains a public health concern, necessitating population education by physicians for safer healthcare practices.

Pain and substance use are highly prevalent and co-occurring conditions that continue to garner increasing clinical and empirical interest. Although nicotine and tobacco, alcohol, and cannabis each confer acute analgesic effects, frequent or heavy use may contribute to the development and progression of chronic pain, and pain may be heightened during abstinence. Additionally, pain can be a potent motivator of substance self-administration, and it may contribute to escalating use and poorer substance-related treatment outcomes. We integrated converging lines of evidence to propose a reciprocal model in which pain and substance use are hypothesized to interact in the manner of a positive feedback loop, resulting in the exacerbation and maintenance of both conditions over time. Theoretical mechanisms in bidirectional pain-substance use relations are reviewed, including negative reinforcement, social cognitive processes, and allostatic load in overlapping neural circuitry. Finally, candidate transdiagnostic factors are identified, and we conclude with a discussion of clinical implications and future research directions. Expected final online publication date for the Annual Review of Clinical Psychology Volume 15 is May 7, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Typically, for measurements with high dynamic range, the range is reduced by using the square root transform. By using non-integer roots coupled with systematic experimental design, improvements to the measurements may be obtained. The effect of using non-integer root transformation was evaluated using high-resolution mass spectrometry (HRMS) combined with nano-electrospray ionization (Nano-ESI) to differentiate 23 samples of Cannabis. The mass spectra were evaluated and classified using different mass resolving powers and non-integer root transformations. Classification was achieved by super partial least squares discriminant analysis (sPLS-DA), support vector machine (SVM), and SVM classification tree type entropy (SVMTreeH). The 2.5 root transformation gave the best overall performance at different resolving powers for chemical profiling from a multilevel factorial experimental design using 2 factors and more than 4 levels. Response surface modeling using a cubic polynomial model of the sPLS-DA prediction accuracies yielded optima at 0.005 for resolving power and 2.3 for the root transformation. Root transformation is an important spectral preprocessing tool for decreasing the dynamic range, so that the relative variance of smaller but more important features may be inflated.

With the increasing push to legalize cannabis in Western nations, there is a need to gage the potential impact of this policy change on vulnerable populations, such as those with mental illness, including schizophrenia, mood, and anxiety disorders. This is particularly important as there are strong motives in these individuals to seek short-term reward (e.g., "getting high"). Nonetheless, data to support the beneficial effects of cannabis use in psychiatric populations are limited, and potential harms in patients with psychotic and mood disorders have been increasingly documented. This article reviews the effects of cannabis in people with mental illness. Then, we provide a reconciliation of the addiction vulnerability and allostatic hypotheses to explain co-morbidity addiction in mentally ill cannabis users, as well as to further aid in developing a rational framework for the assessment and treatment of problematic cannabis use in these patients.

The treatment of infantile spasms is challenging, especially in the context of the following: (1) a severe phenotype with high morbidity and mortality; (2) the urgency of diagnosis and successful early response to therapy; and (3) the paucity of effective, safe, and well-tolerated therapies. Even after initially successful treatment, relapse risk is substantial and the most effective therapies pose considerable risk with long-term administration. In evaluating any treatment for infantile spasms, the key short-term outcome measure is freedom from both epileptic spasms and hypsarrhythmia. In contrast, the most important long-term outcomes are enduring seizure-freedom and measures of intellectual performance in later childhood and adulthood. First-line treatment options-namely hormonal therapy and vigabatrin-display moderate to high efficacy but also exhibit substantial side-effect burdens. Data on efficacy and safety of each class of therapy, as well as the combination of these therapies, are reviewed in detail. Specific hormonal therapies (adrenocorticotropic hormone and various corticosteroids) are contrasted. Those etiologies that prompt specific therapies are reviewed briefly, as are an array of second-line therapies supported by less-compelling data. The ketogenic diet is discussed in greater detail, with a focus on the limitations of numerous available studies that generally suggest that it is efficacious. Special discussion is allocated to cannabidiol-the investigational therapy that has received the most attention, and which is already in use in the form of various artisanal cannabis extracts. Finally, a treatment algorithm reflecting the concepts and controversies discussed in this review is presented.

Despite federal prohibition of medical marijuana possession, sale, and use, marijuana use continues to escalate as state legalization persists and expands. The purpose of this discussion is to provide a brief summary of the evidence regarding both potential benefits and risks of medical marijuana use.

Research into comorbidity of alcohol and cannabis use disorders has resulted in inconsistent findings, especially among simultaneous users, who used alcohol and cannabis together on a single occasion. This study investigated the association of alcohol and cannabis use disorders among simultaneous users using a network perspective, which considers direct relationships between symptoms. We used a subset of simultaneous alcohol and cannabis users driven from the representative population-based sample of young Swiss men cohort study on substance use risk factors (C-SURF) (n = 1559 at baseline and n = 991 at follow-up). Self-reported symptoms of alcohol and cannabis use disorders were collected. Network analyses included network estimation, visualization, and community detection tests. Alcohol and cannabis use symptoms were separated in two distinct clusters, with few paths between them (eleven positive edges at baseline, three at follow-up). Withdrawal symptoms were likely to connect the two disorders at baseline, but not at follow-up. Alcohol and cannabis use disorders appeared as separate disorders among simultaneous users. Our findings mitigated previous findings on the detrimental association between alcohol and cannabis use. Future studies should incorporate network analyses as a means to study comorbidity in other community and clinical samples to confirm our preliminary findings.

Individual and family characteristics early on in life are associated with adolescent smoking; however, their role with regard to long-term tobacco smoking trajectories into young adulthood is not well-known, which is what we set out to study using data from a longitudinal community-based cohort.We used data from 2,025 youths in France (12-26 years at baseline, 16 years of follow-up), participating in the longitudinal TEMPO cohort study. First, we modeled smoking trajectories from adolescence onwards using Group-Based Trajectory Modeling, by using the declared consumption of cigarettes at different ages. Second, among trajectories of smokers, associations with individual and family characteristics in childhood and adolescence were studied using multinomial logistic regression.We observed 5 smoking trajectories: non-smokers (62.3%), 3 groups of persistent smokers with different levels of tobacco use (low, intermediate, high), and a group characterized by high-level smoking followed by cessation. Among participants who were lifetime smokers (n = 763), the trajectory of tobacco use was associated with early substance use initiation, academic attainment, grade retention, and parental smoking. Early tobacco and cannabis use initiation predicted high-level tobacco use, whether it persisted (OR 2.29, 95% CI 1.23-4.28) or not (OR 2.99, 95% CI 1.59-5.63). Grade retention and parental smoking predicted persistent smoking of intermediate (respectively OR 1.53, 95% CI 1.03-1.92; OR 1.74, 95% CI 1.03-2.92) or high level use (respectively OR 1.74, 95% CI 1.07-2.85; OR 1.70, 95% CI 0.91-3.18). Poor academic attainment predicted all 3 smoking trajectories, especially persistent high-level smoking (no high school degree: OR 5.29, 95% CI 1.65-16.97, vocational degree: OR 1.94, 95% CI 0.99-3.80).Tobacco smoking trajectories from adolescence to adulthood are associated with early substance use initiation, parental smoking, and academic difficulties.

Harms and benefits of opioids for chronic noncancer pain remain unclear.To systematically review randomized clinical trials (RCTs) of opioids for chronic noncancer pain.The databases of CENTRAL, CINAHL, EMBASE, MEDLINE, AMED, and PsycINFO were searched from inception to April 2018 for RCTs of opioids for chronic noncancer pain vs any nonopioid control.Paired reviewers independently extracted data. The analyses used random-effects models and the Grading of Recommendations Assessment, Development and Evaluation to rate the quality of the evidence.The primary outcomes were pain intensity (score range, 0-10 cm on a visual analog scale for pain; lower is better and the minimally important difference [MID] is 1 cm), physical functioning (score range, 0-100 points on the 36-item Short Form physical component score [SF-36 PCS]; higher is better and the MID is 5 points), and incidence of vomiting.Ninety-six RCTs including 26 169 participants (61% female; median age, 58 years [interquartile range, 51-61 years]) were included. Of the included studies, there were 25 trials of neuropathic pain, 32 trials of nociceptive pain, 33 trials of central sensitization (pain present in the absence of tissue damage), and 6 trials of mixed types of pain. Compared with placebo, opioid use was associated with reduced pain (weighted mean difference [WMD], -0.69 cm [95% CI, -0.82 to -0.56 cm] on a 10-cm visual analog scale for pain; modeled risk difference for achieving the MID, 11.9% [95% CI, 9.7% to 14.1%]), improved physical functioning (WMD, 2.04 points [95% CI, 1.41 to 2.68 points] on the 100-point SF-36 PCS; modeled risk difference for achieving the MID, 8.5% [95% CI, 5.9% to 11.2%]), and increased vomiting (5.9% with opioids vs 2.3% with placebo for trials that excluded patients with adverse events during a run-in period). Low- to moderate-quality evidence suggested similar associations of opioids with improvements in pain and physical functioning compared with nonsteroidal anti-inflammatory drugs (pain: WMD, -0.60 cm [95% CI, -1.54 to 0.34 cm]; physical functioning: WMD, -0.90 points [95% CI, -2.69 to 0.89 points]), tricyclic antidepressants (pain: WMD, -0.13 cm [95% CI, -0.99 to 0.74 cm]; physical functioning: WMD, -5.31 points [95% CI, -13.77 to 3.14 points]), and anticonvulsants (pain: WMD, -0.90 cm [95% CI, -1.65 to -0.14 cm]; physical functioning: WMD, 0.45 points [95% CI, -5.77 to 6.66 points]).In this meta-analysis of RCTs of patients with chronic noncancer pain, evidence from high-quality studies showed that opioid use was associated with statistically significant but small improvements in pain and physical functioning, and increased risk of vomiting compared with placebo. Comparisons of opioids with nonopioid alternatives suggested that the benefit for pain and functioning may be similar, although the evidence was from studies of only low to moderate quality.

Increases in electronic media communication (EMC) and decreases in face-to-face peer contact in the evening (FTF) have been thought to explain the recent decline in adolescent substance use (alcohol, tobacco, cannabis). This study addresses this hypothesis, by examining associations between (time trends in) EMC, FTF, and substance use in more than 25 mainly European countries.Using 2002-2014 data from the international Health Behaviour in School-aged Children (HBSC) study, we ran multilevel logistic regression analyses to investigate the above associations.National declines in substance use were associated with declines in FTF, but not with increases in EMC. At the individual level, both EMC and FTF related positively to substance use. For alcohol and cannabis use, the positive association with EMC was stronger in more recent years. Associations between EMC and substance use varied across countries, but this variation could not be explained by the proportion of young people using EMC within countries.Our research suggests that the decrease in FTF, but not the increase in EMC, plays a role in the recent decrease in adolescent substance use.

Cannabis exerts its psychoactive effect through cannabinoid receptors that are widely distributed across the cortical surface of the human brain. It is suggested that cannabis use may contribute to structural alterations across the cortical surface. In a large, multisite dataset of 120 controls and 141 cannabis users, we examined whether differences in key characteristics of the cortical surface - including cortical thickness, surface area, and gyrification index were related to cannabis use characteristics, including (i) cannabis use vs. non-use, (ii) cannabis dependence vs. non-dependence vs. non-use, and (iii) early adolescent vs. late adolescent onset of cannabis use vs. non-use. Our results revealed that cortical morphology was not associated with cannabis use, dependence, or onset age. The lack of effect of regular cannabis use, including problematic use, on cortical structure in our study is contrary to previous evidence of cortical morphological alterations (particularly in relation to cannabis dependence and cannabis onset age) in cannabis users. Careful reevaluation of the evidence on cannabis-related harm will be necessary to address concerns surrounding the long-term effects of cannabis use and inform policies in a changing cannabis regulation climate.

To characterize the socio-demographic characteristics, medical conditions, and psychiatric comorbidities of users of marijuana for medical and non-medical purposes.Data were from the National Epidemiological Survey on Alcohol and Related Conditions III, a US nationally representative in-person interview of 36,309 adults age ≥18 years in 2012-2013.In relation to non-medical only users (n = 3339), combined (n = 362) and medical only (n = 82) users had higher prevalence of every medical condition examined. As compared to the combined use group, those using marijuana only for medical purposes were much less likely to have anxiety, alcohol, or non-medical prescription opioid use disorders.Medical-only users appear to use it for evidence-based medical reasons and have lower prevalence of substance use disorder than other marijuana users. Nonetheless, because most medical marijuana users also use non-medically, screening for psychiatric disorders and prevention efforts for cannabis use disorder should be implemented when authorizing medical marijuana.

Opioid misuse constitutes a significant public health problem and is associated with a host of negative outcomes. Despite efforts to curb this increasing epidemic, opioids remain the most widely prescribed class of medications. Prescription opioids are often used to treat chronic pain despite the risks associated with use, and chronic pain remains an important factor in understanding this epidemic. Cannabis is another substance that has recently garnered attention in the chronic pain literature, as increasing numbers of individuals use cannabis to manage chronic pain. Importantly, the co-use of substances generally is associated with poorer outcomes than single substance use, yet little work has examined the impact of opioid-cannabis co-use.The current study examined the use of opioids alone, compared to use of opioid and cannabis co-use, among adults (n = 450) with chronic pain on mental health, pain, and substance use outcomes.Results suggest that, compared to opioid use alone, opioid and cannabis co-use was associated with elevated anxiety and depression symptoms, as well as tobacco, alcohol, cocaine, and sedative use problems, but not pain experience.These findings highlight a vulnerable population of polysubstance users with chronic pain, and indicates the need for more comprehensive assessment and treatment of chronic pain.

The co-use of tobacco and cannabis is a common practice worldwide and carries with it substantial public health burden. Few interventions exist that target both substances and little is known about quit interest, treatment preferences, and drug substitution during past cessation attempts, which is critical to guide the development of treatment strategies. The goal of this study was to provide descriptive information regarding quit interest, treatment preferences, and perceived drug substitution among adult (age 18 +) cannabis-tobacco co-users. Participants (N = 282) from two independent survey samples (recruited from Amazon Mechanical Turk) from across the United States were combined. Among all participants, 57% were female, 79% were White, and average age was 33.31 (SD = 9.54) years old. Approximately 80% had tried to quit smoking cigarettes at least once, while 40% had tried to quit using cannabis at least once. Of those who tried to quit, 50% self-reported a perceived increase in their cannabis use during tobacco cessation and 62% self-reported a perceived increase in their tobacco use during cannabis cessation. Average quit interest (10-point scale) for cannabis was 2.39 (SD = 2.35) and for tobacco was 7.07 (SD = 2.90). Results of this study suggest that tobacco use should be addressed among cannabis-tobacco co-users, but interventions should consider lack of interest in cannabis cessation. Reduction-based strategies for cannabis use appear to be more acceptable to this nontreatment-seeking, co-using population. Drug substitution during quit attempts for one substance should be further explored as an important treatment consideration. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Hempseed has achieved a growing popularity in human nutrition, particularly regarding essential amino acids and fatty acids. The multiple positive attributes of hempseed have led to the further study of its constituents. In this study, hempseed extract containing phenylpropionamides (TPA) was obtained and its chemical profile and content were obtained using high-performance liquid chromatography technology based on previous study. The anti-neuroinflammatory effect of TPA extract was evaluated using a lipopolysaccharide (LPS)-induced mouse model. Fourteen phenylpropionamides (TPA) were identified in the obtained extract with a total content of 233.52 ± 2.50 μg/mg extract. In mice, TPA prevented the learning and spatial memory damage induced by LPS. Increased brain levels of IL-1β, IL-6, and TNF-α in the LPS-induced mice were reduced by TPA treatment. Furthermore, TPA attenuated LPS-induced hippocampal neuronal damage in mice. This study demonstrates the nutraceutical potential of hempseed from a neuroprotective perspective.

Cannabis allergy has mainly been described following recreational use but some cases also point to cannabis sensitisation as a result of occupational exposure. As a consequence, little is known on the prevalence and clinical phenotype of occupational cannabis allergy. Therefore, this study aims to explore the allergy-associated health risks of occupational cannabis exposure in Belgian police force personnel.81 participants, active in the police force, reporting regular occupational cannabis exposure during the past 12 months, were included. History was combined with a standardised questionnaire on allergies and cannabis exposure.Basophil activation tests (BATs) with a crude cannabis extract and rCan s 3 were performed. In addition, specific (s)IgE rCan s 3 as well as sIgE to house dust mite, six pollen and three mould allergens were quantified.Although 42% of the participants reported respiratory and/or cutaneous symptoms on occupational cannabis exposure, all cannabis diagnostics were entirely negative, except one symptomatic case demonstrating a borderline result. Furthermore, there is no significant difference between the groups with and without symptoms on cannabis exposure in terms of allergenic sensitisations.The origins of the reported respiratory and cutaneous symptoms during cannabis exposure remain elusive but are probably due to non-immune reactions. It should be noted that the study was volunteer-based possibly reflecting an excessive number of symptomatic individuals. Nevertheless, as only one participant reported using fully protective gear, much improvement is needed for reducing the number of symptoms reported on duty, independent of their origin.

Cannabis is among the most widely used substances worldwide. The United States has seen an increase in the number of adult daily cannabis users and in the number of adults diagnosed with cannabis use disorder. However, little work has examined patterns of use or unique subgroups of adult cannabis users, which may be useful in developing targeted treatment interventions for problematic cannabis users. Therefore, the current study used latent profile analysis to identify whether cannabis users can be categorized across distinct subgroups of adult users.The sample included 374 current cannabis using adults (64.2% Male; Mage = 32.6). Cannabis use frequency, quantity, and related problems were used to differentiate subgroups. Further, age, race, emotion dysregulation, affect, anxiety sensitivity, other substance use, and motives for cannabis use were examined as class correlates.Results supported five unique classes of cannabis users, generally ranging from light, infrequent users with few problems to heavy, frequent users with more problems. Additionally, race, negative affectivity, anxiety sensitivity, emotion regulation, cannabis use motives, and alcohol use emerged as unique predictors of class membership. The current findings substantiate past work for heterogeneous latent classes that underlie the larger cannabis using population, however, this study provides novel evidence for subgroups of adult users.The identification of different classes of cannabis users may inform future treatment interventions, and ultimately, lead to the development of personalized treatments for each class based on correlates of group membership.

Peroxisome proliferator-activated receptors (PPARs) are a family of ligand-activated nuclear transcription factors, with three characterized subtypes: PPARα, PPARβ/δ, and PPARγ. The biological correlation between the two PPAR subtypes PPARα and γ and carcinogenesis is well-characterized; however, substantially less is known about the biological functions of PPARβ/δ. PPARβ/δ has been reported to repress transcription when PPARβ/δ and PPARα or PPARγ are simultaneously expressed in some cells, and MDA-MB-231 cells express functional levels of PPARβ/δ. We have previously reported that Δ9-tetrahydrocannabinol (Δ9-THC), a major cannabinoid component of the drug-type cannabis plant, can stimulate the expression of fatty acid 2-hydroxylase (FA2H) via upregulation of PPARα expression in human breast cancer MDA-MB-231 cells. Although the possibility of an inhibitory interaction between PPARα and PPARβ/δ has not been demonstrated in MDA-MB-231 cells, we reasoned if this interaction were to exist, Δ9-THC should make PPARα free to achieve FA2H induction. Here, we show that a PPARβ/δ-mediated suppression of PPARα function, but not of PPARγ, exists in MDA-MB-231 cells and Δ9-THC causes FA2H induction via mechanisms underlying the cancellation of PPARβ/δ-mediated inhibition of PPARα, in addition to the upregulation of PPARα.

Cannabis is the most commonly used illicit drug and is known to alter state of consciousness and impair neurocognitive function. However, the mechanisms underlying these effects have yet to be fully elucidated. Rodent studies suggest that Δ9-tetrahydrocannabinol (THC) activates dopaminergic neurons in the limbic system, subsequently enhancing dopamine, which is implicated in the rewarding effects of cannabis. Additional evidence suggests that THC may act indirectly on dopamine firing by modulating GABA and glutamate release. This double-blind, placebo-controlled study assessed the acute influence of two doses of THC on brain kinetics of glutamate, GABA, and dopamine, in relation to behavioral outcomes, by using magnetic resonance spectroscopy and functional magnetic resonance imaging. Twenty occasional cannabis users received acute doses of cannabis (300 µg/kg THC) and placebo, in one of two dose regimes (full dose and divided dose), during two separate testing days. Administration of THC increased striatal glutamate concentrations, and dopamine as indicated by a reduction in functional connectivity (FC) between the nucleus accumbens (NAc) and cortical areas. Alterations in glutamate and FC were dose dependent and evident in the full dose group where THC serum concentrations exceeded 2 ng/ml at T-max. Average glutamate changes correlated strongly with FC alterations. Additionally, THC induced changes in FC correlated with feelings of subjective high and decreased performance on an attention task. Taken together, this suggests that THC elicits subjective and cognitive alterations via increased striatal dopaminergic activity and loss of corticostriatal connectivity, which is associated with an increase in striatal glutamate.

Sexual minority women (SMW) report greater rates of cannabis use. Posttraumatic stress disorder (PTSD) symptom severity is related to greater cannabis use among SMW, and it is theorized that this is due to SMW using cannabis in an attempt to manage negative affectivity associated with PTSD symptoms. However, this is the first known study to test this hypothesis. Among undergraduate women who endorsed lifetime cannabis use (N = 439, 10.5% self-identified SMW), SMW reported greater rates of cannabis use, more frequent cannabis use, greater coping-motivated use, and greater PTSD symptom severity than heterosexual women. Serial mediation analyses revealed that SMW reported more frequent cannabis use via the serial effect of PTSD symptom severity and coping-motivated cannabis use. Given the high rates of trauma exposure and cannabis use among SMW, findings suggest that SMW could benefit from exposure-based interventions in addition to cognitive behavioral skills that would teach them more adaptive strategies to manage negative affect associated with trauma exposure and PTSD symptoms.

Cannabis is the most commonly used illicit drug among general and pregnant populations. Despite recommendations to abstain from cannabis use, its use is increasing during the perinatal period. In this integrative review, we aim to understand women's perspectives about the health aspects of perinatal cannabis use. The following databases were searched: MEDLINE, PsycInfo, EMBASE, and CINAHL. We included quantitative and qualitative studies with a primary focus on perinatal cannabis use. The methodological quality of the included studies was appraised using appropriate checklists. Extracted data were integrated into a single data matrix and iteratively compared across studies to summarize and synthesize the data. Full text of 33 citations was retrieved and reviewed of which 6 studies met the inclusion criteria. Women who continued to use cannabis during pregnancy often perceived no general or pregnancy-specific risk compared to nonusers. The uncertainty regarding adverse perinatal consequences, its perceived therapeutic effects, and lower costs of cannabis compared to that of cigarettes contributed to cannabis use. A lack of communication with health care providers regarding the health aspects of cannabis was evident. Women perceived this lack of counseling as an indication that adverse outcomes associated with cannabis use are not significant. Women's perceptions of health risks associated with cannabis use are important factors in the decision-making process regarding use or cessation, particularly as legal concerns are fading away. A discussion about health concerns surrounding cannabis use may influence women's perceptions of risk and help them to make informed choices.

Introducction. The purpose of this study was to analyze the relationship between emotional and behavioral difficulties and suicidal ideation, bullying and cyberbullying, and substance use in adolescents.The sample consisted of a total of 1,664 participants (M=16.12 years, SD=1.36, range 14-19 years, 697 males), selected by stratified random sampling. The instruments used were the Strengths and Difficulties Questionnaire, the Paykel Suicide Scale, the Cyberbullying- Brief Questionnaire, the Modified Substance Consumption Questionnaire, and the Oviedo Infrequency Response Scale.The results showed that 7.7% of adolescents obtained risk scores of poor mental health, and 13.4% would be in the limit score range. In addition, the results indicated that adolescents who showed a possible risk of emotional and behavioral mental health problems also present greater suicidal ideation, behaviors related to bullying and cyberbullying (perception, victimization), and substance use, specifically tobacco and cannabis.These results increase awareness of the importance of adolescents’ mental health, improve the training of health professionals and guide the implementation of measures to promote health and reduce the risk factors for suicide, school bullying and of substance use and abuse.

Synthetic cannabinoids (SCs) are novel psychoactive substances that are easily acquired, widely abused as a substitute for cannabis, and associated with cardiotoxicity and seizures. Although the structural bases of these compounds are scaffolds with known affinity and efficacy at the human cannabinoid type-1 receptor (hCB1), upon ingestion or inhalation they can be metabolized to multiple chemical entities of unknown pharmacological activity. A large proportion of these metabolites are hydroxylated on the pentyl chain, a key substituent that determines receptor affinity and selectivity. Thus, the pharmacology of SC metabolites may be an important component in understanding the in vivo effects of SCs. We examined nine SCs (AB-PINACA, 5F-AB-PINACA, ADB/MDMB-PINACA, 5F-ADB, 5F-CUMYL-PINACA, AMB-PINACA, 5F-AMB, APINACA, and 5F-APINACA) and their hydroxypentyl (either 4-OH or 5-OH) metabolites in [3H]CP55,940 receptor binding and the [35S]GTPγS functional assay to determine the extent to which these metabolites retain activity at cannabinoid receptors. All of the SCs tested exhibited high affinity (<10 nM) and efficacy for hCB1 and hCB2 The majority of the hydroxypentyl metabolites retained full efficacy at hCB1 and hCB2, albeit with reduced affinity and potency, and exhibited greater binding selectivity for hCB2 These data suggest that phase I metabolites may be contributing to the in vivo pharmacology and toxicology of abused SCs. Considering this and previous reports demonstrating that metabolites retain efficacy at the hCB1 receptor, the full pharmacokinetic profiles of the parent compounds and their metabolites need to be considered in terms of the pharmacological effects and time course associated with these drugs.

The purpose of this systematic review was to examine the association and directionality between mental health disorders and substance use among adolescents and young adults in the U.S. and Canada.The following databases were used: Medline, PubMed, Embase, PsycINFO, and Cochrane Library. Meta-analysis used odds ratios as the pooled measure of effect.A total of 3656 studies were screened and 36 were selected. Pooled results showed a positive association between depression and use of alcohol (odds ratio (OR) = 1.50, 95% confidence interval (CI): 1.24⁻1.83), cannabis (OR = 1.29, 95% CI: 1.10⁻1.51), and tobacco (OR = 1.65, 95% CI: 1.43⁻1.92). Significant associations were also found between anxiety and use of alcohol (OR = 1.54, 95% CI: 1.19⁻2.00), cannabis (OR = 1.36, 95% CI: 1.02⁻1.81), and tobacco (OR = 2.21, 95% CI: 1.54⁻3.17). A bidirectional relationship was observed with tobacco use at baseline leading to depression at follow-up (OR = 1.87, CI = 1.23⁻2.85) and depression at baseline leading to tobacco use at follow-up (OR = 1.22, CI = 1.09⁻1.37). A unidirectional relationship was also observed with cannabis use leading to depression (OR = 1.33, CI = 1.19⁻1.49).This study offers insights into the association and directionality between mental health disorders and substance use among adolescents and young adults. Our findings can help guide key stakeholders in making recommendations for interventions, policy and programming.

It has been known for nearly 50 years that cannabis and the psychoactive constituent Δ9-tetrahydrocannabinol (THC) reduce intraocular pressure (IOP). Elevated IOP remains the chief hallmark and therapeutic target for glaucoma, a major cause of blindness. THC likely acts via one of the known cannabinoid-related receptors (CB1, CB2, GPR18, GPR119, GPR55) but this has never been determined explicitly. Cannabidiol (CBD) is a second major constituent of cannabis that has been found to be without effect on IOP in most studies.Effects of topically applied THC and CBD were tested in living mice by using tonometry and measurements of mRNA levels. In addition the lipidomic consequences of CBD treatment were tested by using lipid analysis.We now report that a single topical application of THC lowered IOP substantially (∼28%) for 8 hours in male mice. This effect is due to combined activation of CB1 and GPR18 receptors each of which has been shown to lower ocular pressure when activated. We also found that the effect was sex-dependent, being stronger in male mice, and that mRNA levels of CB1 and GPR18 were higher in males. Far from inactive, CBD was found to have two opposing effects on ocular pressure, one of which involved antagonism of tonic signaling. CBD prevents THC from lowering ocular pressure.We conclude that THC lowers IOP by activating two receptors-CB1 and GPR18-but in a sex-dependent manner. CBD, contrary to expectation, has two opposing effects on IOP and can interfere with the effects of THC.

Aims We present a case of a five-year-old female admitted postoperatively to the Paediatric Critical Care Unit with a history of refractory seizures for which her parents were administering cannabis oil. Methods We discuss the issues surrounding cannabis prescription in Ireland and the role of parental autonomy in medication selection and administration. Results An administration regime was agreed upon following discussion with the child’s parents. Conslusion While this case raised ethical and legal issues, we must also consider parental autonomy and their role as advocate for their child during admission to critical care.

Introduction and Objective: Org27569 is a prototypical allosteric modulator of the cannabinoid receptor 1 (CB1). It belongs to the indole-2-carboxamide scaffold and has been intensively investigated in pharmacology and in structure-activity relationship (SAR) studies. Although azaindoles are rare in natural products and differ only by the presence of an extra ring nitrogen, they were demonstrated as valuable bioisosteres in many pharmacologically important molecules. To extend the SAR investigation of the indole-2-carboxamide class of CB1 allosteric modulators, azaindole (pyrrolopyridine) rings were used to replace the indole ring of Org27569 analogs to explore the potential of azaindole-2-carboxamides as CB1 allosteric modulators. Using 6- and 7-azaindole in lieu of the indole moiety within this class of CB1 allosteric modulators indeed improved the aqueous solubility. Materials and Methods: We synthesized 6- and 7-azaindole-2-carboxamides and their indole-2-carboxamide counterparts. The molecules were evaluated by [3H]CP55,940 binding and [35S]GTPγS binding assays for their allosteric modulation of the CB1 receptor. Results: The 7-azaindole-2-carboxamides lost the ability to bind to the CB1 receptor. The 6-azaindole-2-carboxamides (e.g., 3c and 3d) showed markedly reduced binding affinities to the CB1 receptor in comparison with their indole-2-carboxamide counterparts. However, they behaved similarly as indole-2-carboxamides in potentiating the orthosteric agonist binding and inhibiting the orthosteric agonist-induced G-protein coupling. The results indicated that some azaindole scaffolds (e.g., 6-azaindole) are worth further exploration, whereas the 7-azaindole ring is not a viable bioisostere of the indole ring in the Org27569 class of CB1 allosteric modulators.

Background and Aims: Legalization of cannabis (CB) for both medicinal and, in some states, recreational use, has given rise to increasing usage rates across the country. Of particular concern are indications that frequent CB use may be selectively harmful to the developing adolescent brain compared with adult-onset usage. However, the long-term effects of heavy, adolescent CB use on brain structure and cognitive performance in late-life remain unknown. A critical brain region is the hippocampus (HC), where there is a striking intersection between high concentrations of cannabinoid 1 (CB1) receptors and age-related pathology. Design: We investigated whether older adults (average age=66.6+7.2 years old) with a history of early life CB use show morphological differences in hippocampal subregions compared with older, nonusers. Methods: We performed high-resolution magnetic resonance imaging combined with computational techniques to assess cortical thickness of the medial temporal lobe, neuropsychological testing, and extensive drug use histories on 50 subjects (24 formerly heavy cannabis users [CB+ group] abstinent for an average of 28.7 years, 26 nonusers [CB- group]). We investigated group differences in hippocampal subregions, controlling for age, sex, and intelligence (as measured by the Wechsler Test of Adult Reading), years of education, and cigarette use. Results: The CB+ subjects exhibited thinner cortices in subfields cornu ammonis 1 [CA1; F(1,42)=9.96, p=0.0003], and CA2, 3, and the dentate gyrus [CA23DG; F(1,42)=23.17, p<0.0001], and in the entire HC averaged over all subregions [F(1,42)=8.49, p=0.006]. Conclusions: Negative effects of chronic adolescent CB use on hippocampal structure are maintained well into late life. Because hippocampal cortical loss underlies and exacerbates age-related cognitive decline, these findings have profound implications for aging adults with a history of early life usage. Clinical Trial Registration: ClinicalTrials.gov # NCT01874886.

The use of medical marijuana-both the psychoactive tetrahydrocannabinol and its nonpsychoactive relative cannabidiol-is a growing practice in facilities served by senior care pharmacists. Currently, 30 states have approved its use under a variety of different regulations and for a number of conditions. Its use is bolstered by a growing number of Americans who support legalization of cannabis. Though oral synthetic cannabinoid compounds are approved by the Food and Drug Administration for chemotherapy-induced nausea and vomiting and appetite stimulation associated with AIDS, synthetic products differ from plant-derived products in several ways. In addition, use of these substances has created a regulatory and legal quagmire that differs considerably depending on the state in which the pharmacist practices. In long-term care, pharmacists face an entirely different set of challenges than pharmacists who practice in other settings: Increasingly, long-term care residents and their attending physicians are asking to use medical marijuana. This manuscript discusses how some long-term care facilities are accommodating this substance that federally and in many states is considered illegal. It also discusses some of the challenges faced by pharmacists who work in dispensaries.

Due to renewed interest in the cultivation and production of Italian Cannabis sativa L., we proposed a multi-methodological approach to explore chemically and biologically both the essential oil and the aromatic water of this plant. We reported the chemical composition in terms of cannabinoid content, volatile component, phenolic and flavonoid pattern, and color characteristics. Then, we demonstrated the ethnopharmacological relevance of this plant cultivated in Italy as a source of antioxidant compounds toward a large panel of enzymes (pancreatic lipase, α-amylase, α-glucosidase, and cholinesterases) and selected clinically relevant, multidrug-sensible, and multidrug-resistant microbial strains (Staphylococcus aureus, Helicobacter pylori, Candida, and Malassezia spp.), evaluating the cytotoxic effects against normal and malignant cell lines. Preliminary in vivo cytotoxicity was also performed on Galleria mellonella larvae. The results corroborate the use of this natural product as a rich source of important biologically active molecules with particular emphasis on the role exerted by naringenin, one of the most important secondary metabolites.

Cannabidiol (CBD) is a non-psychotomimetic cannabinoid compound that is found in plants of the genus Cannabis. Preclinical research has suggested that CBD may have a beneficial effect in rodent models of post-traumatic stress disorder (PTSD). This effect is believed to be due to the action of CBD on the endocannabinoid system. CBD has seen a recent surge in research regarding its potential value in a number of neuro-psychiatric conditions. This is the first study to date examining the clinical benefit of CBD for patients with PTSD.This retrospective case series examines the effect of oral CBD administration on symptoms of PTSD in a series of 11 adult patients at an outpatient psychiatry clinic. CBD was given on an open-label, flexible dosing regimen to patients diagnosed with PTSD by a mental health professional. Patients also received routine psychiatric care, including concurrent treatment with psychiatric medications and psychotherapy. The length of the study was 8 weeks. PTSD symptom severity was assessed every 4 weeks by patient-completed PTSD Checklist for the DSM-5 (PCL-5) questionnaires.From the total sample of 11 patients, 91% (n = 10) experienced a decrease in PTSD symptom severity, as evidenced by a lower PCL-5 score at 8 weeks than at their initial baseline. The mean total PCL-5 score decreased 28%, from a mean baseline score of 51.82 down to 37.14, after eight consecutive weeks of treatment with CBD. CBD was generally well tolerated, and no patients discontinued treatment due to side effects.Administration of oral CBD in addition to routine psychiatric care was associated with PTSD symptom reduction in adults with PTSD. CBD also appeared to offer relief in a subset of patients who reported frequent nightmares as a symptom of their PTSD. Additional clinical investigation, including double-blind, placebo-controlled trials, would be necessary to further substantiate the response to CBD that was observed in this study.

As the number of states legalizing marijuana for medical and/or recreational use continues to grow, there are an increasing number of children exposed to marijuana-containing products in homes and communities. Increased exposure leads to a greater probability of accidental ingestion and toxicity. Because marijuana ingestion can cause a dangerous and potentially life-threatening toxicity for children, pediatric health care providers need an increased awareness of the danger. This article describes the growing problem and outlines clinical management as well as prevention. [Pediatr Ann. 2018;47(12):e474-e476.].

The endocannabinoid system is a complex and nearly ubiquitous network of endogenous ligands, enzymes, and receptors that can also be stimulated by exogenous compounds such as those derived from the marijuana plant, Cannabis sativa. Recent data have shown that the endocannabinoid system is fully functional in the skin and is responsible for maintaining many aspects of skin homeostasis, such as proliferation, differentiation, and release of inflammatory mediators. Because of its role in regulating these key processes, the endocannabinoid system has been studied for its modulating effects on both inflammatory disorders of the skin and skin cancer. Although legal restrictions on marijuana as a Schedule I drug in the USA have made studying cannabinoid compounds unfavorable, an increasing number of studies and clinical trials have focused on the therapeutic uses of cannabinoids. This review seeks to summarize the current, and rapidly expanding field of research on the broad potential uses of cannabinoids in inflammatory and neoplastic diseases of the skin.

Cannabis has been used for medicinal purposes for thousands of years. The prohibition of cannabis in the middle of the 20th century has arrested cannabis research. In recent years there is a growing debate about the use of cannabis for medical purposes. The term 'medical cannabis' refers to physician-recommended use of the cannabis plant and its components, called cannabinoids, to treat disease or improve symptoms. Chronic pain is the most commonly cited reason for using medical cannabis. Cannabinoids act via cannabinoid receptors, but they also affect the activities of many other receptors, ion channels and enzymes. Preclinical studies in animals using both pharmacological and genetic approaches have increased our understanding of the mechanisms of cannabinoid-induced analgesia and provided therapeutical strategies for treating pain in humans. The mechanisms of the analgesic effect of cannabinoids include inhibition of the release of neurotransmitters and neuropeptides from presynaptic nerve endings, modulation of postsynaptic neuron excitability, activation of descending inhibitory pain pathways, and reduction of neural inflammation. Recent meta-analyses of clinical trials that have examined the use of medical cannabis in chronic pain present a moderate amount of evidence that cannabis/cannabinoids exhibit analgesic activity, especially in neuropathic pain. The main limitations of these studies are short treatment duration, small numbers of patients, heterogeneous patient populations, examination of different cannabinoids, different doses, the use of different efficacy endpoints, as well as modest observable effects. Adverse effects in the short-term medical use of cannabis are generally mild to moderate, well tolerated and transient. However, there are scant data regarding the long-term safety of medical cannabis use. Larger well-designed studies of longer duration are mandatory to determine the long-term efficacy and long-term safety of cannabis/cannabinoids and to provide definitive answers to physicians and patients regarding the risk and benefits of its use in the treatment of pain. In conclusion, the evidence from current research supports the use of medical cannabis in the treatment of chronic pain in adults. Careful follow-up and monitoring of patients using cannabis/cannabinoids are mandatory.

Positive relationships with family, friends and school staff are consistently linked with health and wellbeing during adolescence, though fewer studies explore how these micro-systems interact to influence adolescent health. This study tests the independent and interacting roles of family, peer and school relationships in predicting substance use, subjective wellbeing and mental health symptoms among 11-16 year olds in Wales. It presents cross-sectional analyses of the 2013 Health Behaviour in School-aged Children survey, completed by 9055 young people aged 11-16 years. Multilevel logistic regression analyses are used to test associations of family communication, family support, relationships with school staff, school peer connectedness, and support from friends, with tobacco use, cannabis use, alcohol use, subjective wellbeing and mental health symptoms. Positive relationships with family and school staff were consistently associated with better outcomes. Support from friends was associated with higher use of all substances, while higher school peer connectedness was associated with better subjective wellbeing and mental health. Better relationships with school staff were most strongly associated with positive subjective wellbeing, and fewer mental health symptoms where pupils reported less family support. Support from friends was associated with higher cannabis use and worse mental health among pupils with lower family support. Relationships with family and school staff may be important in protecting young people against substance use, and improving wellbeing and mental health. Interventions focused on student-staff relationships may be important for young people with less family support. Interventions based on peer support should be mindful of potential harmful effects for pupils with less support from family.

Prevalence of cannabis use among older Americans (aged ≥ 65) appears to be rising, and emerging evidence associates cannabis use with several oral diseases. The burden of oral diseases among older Americans is great, but literature discussing potential implications of increasing rates of cannabis use and the oral health of older persons is lacking. This paper explores the latest trends in prevalence of cannabis use among older Americans and summarizes the literature on the oral health status of older adults and oral effects of cannabis use, and considers broad implications for oral health and public health policy and future research. Further studies on the effects cannabis use on the oral health of older adults are needed. Future research should investigate older subjects' susceptibility to cannabis-related oral diseases, as well as the proportions that develop disease. Policymakers may wish to tackle barriers to access of dental services for the older population, or target subsets of the population that suffer from comparably higher rates of oral diseases, while dental professionals may require training on managing underlying substance use behaviors in addition to clinical oral manifestations.

Adolescent cannabis use is associated with working memory impairment. The present randomized controlled trial assigned adolescents ages 14 to 21 enrolled in cannabis use treatment to receive either working memory training (experimental group) or a control training (control group) as an adjunctive treatment. Cognitive function, drug use, and other outcomes were assessed before and after training. We observed few differences in cognitive, functional, or self-reported drug use outcomes as a function of training group, although tetrahydrocannabinol (THC) urinalysis results favored the experimental group. These findings are similar to previous studies in substance users, which have shown limited transfer effects for working memory training.

Alcohol and cannabis were the two main substances of misuse among certain groups in Sudan, especially young adults. Over the past decade, there has been a surge in the use of other substances, including prescribed drugs, among young people and university students in particular. There are two major shortcomings: first, in the absence of reliable data, the extent of the problem is unknown; second, the preventive and treatment interventions so far being adopted are meagre. To describe the possible causes behind the escalation of this problem and to discuss applicable measures that need to be implemented to control this rapidly growing problem. The paper will highlight the current situation of substance use in Sudan, as well as suggesting preventive measures that need to be taken to curb this problem. Research and evidence-based preventive approaches are desperately needed to aid policy makers in controlling this problem. Culture-specific treatment interventions are also necessary. The implementation of a national substance misuse control strategy is of paramount importance.

In the context of cannabis legalization, an important question among clinicians, policymakers, and the public is whether availability of legal cannabis will significantly reduce consumption (demand) of illegal cannabis. Using paradigms from behavioural economics, we tested the prediction that legal cannabis would be an asymmetrical substitute for illegal cannabis, with legal cannabis operating as a superior commodity based on its regulated status. In a sample of 289 adult cannabis users in Ontario, we found evidence of substitutability for both legal and illegal cannabis, but significantly lower substitutability of illegal for legal cannabis, a pattern that was also present for price elasticity (α) and Pmax. Thus, the data indicated asymmetric substitution such that the availability of legal cannabis substantially decreased demand for illegal cannabis, but a significantly smaller effect in reverse. These results suggest that the introduction of legal cannabis into the market may disrupt and reduce illegal purchases, contributing to the reduction of the potential harms associated with the illegal market. However, in revealing price windows in which legal cannabis is preferred over the contraband alternative, these data also have significant implications for pricing policies.

Adolescent cannabis use has been implicated as a risk factor for schizophrenia; however, it is neither necessary nor sufficient. Previous studies examining this association have focused primarily on the role of the cannabinoid receptor 1 (CB1R) with relatively little known about a key regulatory protein, the cannabinoid receptor interacting protein 1 (CNRIP1). CNRIP1 is an intracellular protein that interacts with the C-terminal tail of CB1R and regulates its intrinsic activity. Previous studies have demonstrated aberrant CNRIP1 DNA promoter methylation in post-mortem in human patients with schizophrenia, and we have recently reported decreased methylation of the CNRIP1 DNA promoter in the ventral hippocampus (vHipp) of a rodent model of schizophrenia susceptibility. To examine whether augmented CNRIP1 expression could contribute to the pathology of schizophrenia, we performed viral-mediated overexpression of CNRIP1 in the vHipp of Sprague Dawley rats. We then tested these rats for behavioral correlates of schizophrenia symptoms, followed by electrophysiology to determine the effects on the dopamine system, known to underlie psychosis. Here, we report that overexpression of vHipp CNRIP1 induces impairments in latent inhibition and social interaction, similar to those observed in individuals with schizophrenia and in rodent models of the disease. Furthermore, rats overexpressing vHipp CNRIP1 displayed a significant increase in ventral tegmental area (VTA) dopamine neuron population activity, a putative correlate of psychosis. These data provide evidence that alterations in CNRIP1 may contribute to the pathophysiology of schizophrenia, as overexpression is sufficient to produce neurophysiological and behavioral correlates consistently observed in rodent models of the disease.

Medicolegal realities surrounding "medical marijuana" or "medical cannabis" are rapidly evolving in the United States. Clinicians are increasingly being asked by patients to share information about or certify them for medical cannabis. In order to engage in informed discussions with patients or be comfortable certifying them in states with medical cannabis laws, clinicians may benefit from an understanding of the current state of medical knowledge about medical cannabis. Intended for the generalist and subspecialist, this review provides an overview of the legal status, pharmacology, benefits, risks, and abuse liability of medical cannabis along with a general framework for counseling patients.

Pre-clinical research supports that cannabinoids reduce opioid dose requirements, but few studies have tested this in humans. This review evaluates ecological and epidemiological studies that have been cited as evidence that medical cannabis use may reduce opioid use and opioid-related harms. Medline and Embase were searched for relevant articles. Data were extracted on study setting, analyses approach, covariates, and outcomes. Eleven ecological and 14 epidemiological studies were found. In ecological studies, states that allow medical cannabis laws have reported a slower rate of increase in opioid overdose deaths compared with states without such laws. These differences have increased over time and persisted after controlling for state sociodemographic characteristics and use of prescription monitoring programmes. Few studies have controlled for other potential confounders such as opioid dependence treatment and imprisonment rates. Some epidemiological studies provide evidence that cannabis availability may reduce opioid use, but are limited by selection bias, cross-sectional designs, and self-reported assessments of the opioid-sparing effects of cannabis. Some epidemiological and ecological studies suggest that cannabis may reduce opioid use and harms, although important methodological weaknesses were identified. Well-designed clinical studies may provide more conclusive evidence on whether cannabinoids can reduce opioid use and related harm.

Nightmares are considered the hallmark of posttraumatic stress disorder (PTSD). Although the characteristics of these distressing dreams may vary with the type of traumatic event, the pathophysiology exposes central dysfunction of brain structures at the level of the hippocampus, amygdala, and locus coeruleus, modulated by neurochemical imbalance in nor-adrenergic, dopaminergic, and serotonin pathways. Underlying comorbid conditions, including other sleep disorders, may contribute to worsening symptoms. Addressing sleep disruption can alleviate the severity of these nocturnal events and augment the effectiveness of other PTSD treatments. The expansion of behavioral treatment modalities for PTSD-related nightmares has been encouraging, but the core of these interventions is heavily structured around memory manipulation and imagery rescripting. A lack of a standardized delivery and a high dropout rate continue to pose significant challenges in achieving successful outcomes. The efficacy of existing pharmacological studies, such as α-adrenergic blocking agents, antidepressants, and atypical antipsychotics, has been undermined by methodological limitations and absence of large randomized controlled trials. This review is aimed at reviewing the available treatment strategies for alleviating nightmares in subjects with PTSD. Given the intricate relationship between PTSD and nightmares, future clinical trials have to adopt a more pragmatic approach focused not only on efficacy of novel interventions but also on adjunctive iteration of existing therapies tailored to individual socio-cultural background.

This study aims to examine the association between depression, anxiety and substance use among Canadian post-secondary students.This study used data from the spring 2016, American College Health Association - National College Health Assessment II (ACHA-NCHA II) survey. It includes 43,780 college students from 41 Canadian post-secondary institutions. The exposure variables of interest were alcohol, cannabis and tobacco use, and the outcome variables of interest were diagnosis or treatment for depression and/or anxiety. Descriptive statistics, univariate and multivariate logistic regression models were used to analyze our data.Our study found that 14.7% of post-secondary students were diagnosed or treated for depression and 18.4% for anxiety within the past 12 months. Among current (past 30 days) substance use, it was reported that alcohol (69.3%), cannabis (17.9%) and tobacco (11%) were the most common. There was a significant association between depression and current tobacco use (OR =1.36, 95% CI: 1.22-1.52, P<0.001) and current cannabis use (OR =1.17, 95% CI: 1.05-1.31, P<0.001). There was also a gender-specific association between anxiety and female alcohol users (OR =1.41, 95% CI: 1.24-1.62, P<0.001).The results of this study found significant associations between depression, tobacco use and cannabis use, and anxiety and alcohol use among post-secondary students. These conditions should be screened concurrently for improved outcomes among this vulnerable population.

The use of cannabis for therapeutic and recreational purposes is growing exponentially. Nevertheless, substantial questions remain concerning the potential cognitive and affective side-effects associated with cannabis exposure. In particular, the effects of specific marijuana-derived phytocannabinoids on neural regions such as the prefrontal cortex (PFC) are of concern, given the role of the PFC in both executive cognitive function and affective processing. The main biologically active phytocannabinoids, ∆-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), interact with multiple neurotransmitter systems important for these processes directly within the PFC. Considerable evidence has demonstrated that acute or chronic THC exposure may induce psychotomimetic effects, whereas CBD has been shown to produce potentially therapeutic effects for both psychosis and/or anxiety-related symptoms. Using an integrative combination of cognitive and affective behavioral pharmacological assays in rats, we report that acute intra-PFC infusions of THC produce anxiogenic effects while producing no impairments in executive function. In contrast, acute infusions of intra-PFC CBD impaired attentional set-shifting and spatial working memory, without interfering with anxiety or sociability behaviors. In contrast, intra-PFC CBD reversed the cognitive impairments induced by acute glutamatergic antagonism within the PFC, and blocked the anxiogenic properties of THC, suggesting that the therapeutic properties of CBD within the PFC may be present only during pathologically aberrant states within the PFC. Interestingly, the effects of PFC THC vs. CBD were found to be mediated through dissociable CB1 vs. 5-HT1A-dependent receptor signaling mechanisms, directly in the PFC.

Alcoholic gastritis, a superficial erosive disease of the stomach, is a common manifestation of risky alcohol use. In contrast, cannabis which is frequently co-used with alcohol suppresses gastric acidity and might counteract the deleterious effect of alcohol on the gastric mucosa. However, no clinical study has examined the impact of cannabis use on the development of alcoholic gastritis among risky alcohol users.We analyzed hospital discharge records of adults (age ≥ 18 years), from 2014 of the Nationwide Inpatient Sample, with a diagnosis of risky alcohol use (n = 316,916). We used a propensity-based matching algorithm to match cannabis users to nonusers on 1:1 ratio (30,713: 30,713). We then measured the adjusted relative risk (aRR) for having alcoholic gastritis using conditional Poisson regression models with generalized estimating equations.Our study revealed that among risky alcohol users, cannabis co-users have a lower prevalence of alcoholic gastritis compared to noncannabis users (1,289 [1,169 to 1,421] vs. 1,723 [1,583 to 1,875] per 100,000 hospitalizations for risky alcohol use), resulting in a 25% decreased probability of alcoholic gastritis (aRR: 0.75 [0.66 to 0.85]; p-value <0.0001). Furthermore, dependent cannabis usage resulted in a lower prevalence of alcoholic gastritis when compared to both nondependent cannabis users (0.72 [0.52 to 0.99]) and to noncannabis users (0.56 [0.41 to 0.76]).We reveal that risky alcohol drinking combined with cannabis use is associated with reduced prevalence of alcohol-associated gastritis in patients. Given increased cannabis legislation globally, understanding whether and how the specific ingredients in cannabis plant extract can be used in the treatment of alcoholic gastritis is paramount. In this regard, further molecular mechanistic studies are needed to delineate the mechanisms of our novel findings not only for alcoholic gastritis but also for gastritis from other causes.

Though many interventions have been shown to be effective in helping smokers quit, outcomes may differ between light and heavy smokers. We identified differences in baseline characteristics and post-intervention cessation rates among smoker groups at two safety-net hospitals.We retrospectively analyzed cessation rates in 1,604 patients randomized to either a quitline referral (1-2 telephone counseling sessions) or intensive counseling program (7 telephone sessions). Participants were stratified into light-intermittent (smoked on ≤24 of last 30 days), light-daily (smoked on >24/30 days, 1-9 cigarettes per day (CPD)), or heavy smokers (smoked on >24/30 days, ≥10 CPD). We compared baseline characteristics between smoker types using chi-squared tests, then identified predictors of 30-day abstinence using a multivariable model.Compared to light-daily and light-intermittent smokers, heavy smokers were more likely to be white, male, concomitant e-cigarette users, to have high-risk alcohol use, to have used quitting aids previously, to have current or lifetime substance use (excluding cannabis) and have lower confidence in quitting. However, in multivariable analysis, smoker type was not significantly associated with cessation. The statistically significant predictors of cessation at 6 months were higher confidence in quitting and enrollment in the intensive counseling intervention.Smoker type (light-intermittent, light-daily, or heavy) does not independently predict success in a cessation program. However, smoker type is strongly associated with patients' confidence in quitting, which may be one predictor of cessation.This study of two safety-net hospitals emphasizes that the number of cigarettes smoked per day does not independently predict smoking cessation. Additionally, heavy smokers are at highest risk for the detrimental health effects of tobacco, yet have lower confidence and motivation to quit. Confidence in quitting may be one factor that affects cessation rates, however further study is needed to identify which other attributes predict cessation. These findings suggest that smoker type may still be a useful proxy for predicting cessation, and that interventions specifically designed for and validated in heavy smokers are needed to better aid these individuals.

As a consequence of the Presidential Decree that reforms and additions the General Statute of Health with regard to medicinal and scientific use of tetrahydrocannabinol, its isomers and stereochemical variants, the National Academy of Medicine of Mexico declares its position in favor of regulating investigation and national production thereof.

This study sought to estimate the number of illicit retailers and the average price of cannabis in the largest municipality in each province and territory in Canada by obtaining information from retailers.Online search engines were used to identify retailers in each municipality. The advertised prices for various volumes of the least expensive, most expensive, and most popular dry herb were determined using the retailer's website, Weedmaps, or Leafly. Data was collected between October 2017 and May 2018, including two waves in Toronto to examine changes over a five-month period.Across the 13 municipalities, 997 cannabis retailers were identified, including 215 physical storefronts. The average price per gram of cannabis was $10.02, $7.80, and $12.30 for the most popular, least expensive, and most expensive strains, respectively. The price-per-gram decreased as purchase volume increased: purchasing one-eighth of an ounce and one ounce of cannabis led to savings of up to 9% and 27%, respectively. Prices were consistent across municipalities, although the number of outlets varied greatly. Prices were similar between storefronts and delivery-only services; however, delivery services offered larger discounts for cannabis purchased by the ounce. The five-month comparison in Toronto revealed modest changes in the number of retailers and more pronounced changes in the price of the most popular and least expensive strains.The findings depict a well-established retail cannabis market in Canada in the year prior to legalization. The average advertised price of the most popular cannabis varieties was approximately $10, which aligns with the projected retail price of cannabis from licensed sources following legalization in Canada.

Cannabis use disorder (CUD) is prevalent and demand for treatment is increasing, yet few individuals engage in formal treatment and the efficacy of established interventions for CUD is modest. Existing clinical trials evaluating psychosocial and pharmacological treatments for CUD have incorporated a wide variety of measures for assessing cannabis use outcomes, including abstinence, self-reported frequency and quantity used, withdrawal, use/dependence severity, and other psychosocial outcomes. The heterogeneity of measures and outcomes has limited quantitative analyses of the comparative effectiveness of existing interventions. The purpose of this systematic review is to: 1) identify and characterize approaches for measuring cannabis use in existing CUD intervention trials, including abstinence, frequency and quantity of use, and 2) summarize measures used to assess treatment efficacy in other outcome domains (e.g., cannabis use severity, psychosocial functioning, cannabis withdrawal), and provide a platform for future research to evaluate which outcome measures are most likely to reflect treatment efficacy and clinically significant improvement in other outcome domains.

Addictive disorders are characterized by impulsive behavior that leads to difficulties in preventing certain behaviors despite negative consequences. This symptom predisposes to a vulnerability in developing addictive disorders and is also aggravated by the addiction process itself. As such, understanding the underlying mechanisms of impulsivity is a challenge for understanding the pathophysiology of addiction. One common link between impulsivity and addiction is that both involve actions and decisions that are realized faster than they should be in time. Impulsive traits increase the tendency to choose immediate gratification instead of delayed gratification even when preferred. This observation suggests a relationship between impulsivity and time processing. To better understand this relationship, we reviewed the literature that describes the relationship between time processing and impulsivity in addictive disorders in humans. Despite a lack of literature concerning this question in alcohol, cannabis and gambling disorders, we highlight that addictive behaviors are a good model for understanding the pathophysiology of impulsivity, and could help us to better understand the relationship between time perception and impulsivity.

Cannabis is one of the most commonly used drugs among adolescents, with initial use beginning between the ages of 12 to 17. Although often perceived as a 'soft drug', both short- and long-term use have been associated with numerous adverse outcomes, including cognitive impairment, increased risk of substance abuse, and heightened risk of psychosis or schizophrenia in individuals with a predisposition. Further, the severity of these impairments is closely linked to initiation of use, i.e. earlier use increases risk. It has been suggested that adolescent vulnerability to the adverse consequences of cannabis use is due to ongoing brain development occurring during this time. Indeed, the adolescent brain continues to be remodeled well into adolescence and early adulthood, particularly in the prefrontal cortex (PFC). The medial prefrontal cortex (mPFC) has been implicated in reward processing and decision-making and alterations in mPFC development due to adolescent cannabis exposure could impair these functions. To model the effects of cannabis on mPFC function, we administered the synthetic cannabinoid WIN 55, 212-2 (WIN) to male and female rats from postnatal day 30-60. Once animals reached adulthood, we used a Probabilistic Reward (PR) choice task to elicit PFC activity and measure how patterns of activity to task-related events were modulated by adolescent WIN-treatment. Adult animals showed subtle effects of WIN-treatment on choice patterns. During task performance, mPFC activity elicited by lever press at the time of choices and reward delivery following choices were reduced in WIN-treated animals. This lasting effect of WIN suggests an impairment of the maturation of excitatory-inhibitory balance of signals in mPFC during adolescence, which may alter executive function into adulthood.

Wastewater-based epidemiology (WBE) is a rapidly developing discipline that has the potential to monitor real-time data on regional and temporal differences regarding the use of illicit drugs. With WBE, metabolic products discharged for drug consumption are rapidly collected by sewage systems, which provide valuable evidence on the types and quantities of drugs consumed by a given community. In this study, the samples were collected from the wastewaters entering the facilities in Seyhan and Yuregir Waste Water Treatment Plants (WWTPs), in Adana Province. Composite wastewater analysis was performed by using liquid chromatography tandem mass spectrometry (LC-MS/MS) and the analysis revealed multiple drugs including cocaine and its main metabolite, benzoylecgonine, amphetamine-like stimulants including amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA), and 3,4-methylenedioxyethamphetamine (MDEA), opiates including morphine, codeine, heroin metabolite 6-acetylmorphine (6-MAM), the metabolite of cannabis, 11-nor-carboxy-THC (THC-COOH), and the main metabolite of Δ9-tetrahydrocannabinol (THC), 11-hydroxy (THC-OH). Mean drug consumption rates were as follows: cocaine, 0.18; amphetamine, 0.43; methamphetamine, 0.06; MDMA (ecstasy), 1.30; heroin, 1.03; THC (marijuana), 28.60 doses/day/1000 persons (15-64years). The consumption rates for some illicit drugs showed a significant difference between seasons, regions, and weekdays-weekends.

Cannabis is one of the most widely used drugs worldwide. Cannabis use disorder is characterised by recurrent use of cannabis that causes significant clinical and functional impairment. There are no approved pharmacological treatments for cannabis use disorder. One approach is to potentiate endocannabinoid signalling by inhibiting fatty acid amide hydrolase (FAAH), the enzyme that degrades the endocannabinoid anandamide. We aimed to test the efficacy and safety of the FAAH-inhibitor PF-04457845 in reduction of cannabis withdrawal and cannabis use in men who were daily cannabis users.We did a double-blind, placebo-controlled, parallel group phase 2a trial at one site in men aged 18-55 years with cannabis dependence according to DSM-IV criteria (equivalent to cannabis use disorder in DSM-5). After baseline assessments, participants were randomly assigned (2:1) to receive PF-04457845 (4 mg per day) or placebo using a fixed block size of six participants, stratified by severity of cannabis use and desire to quit. Participants were admitted to hospital for 5 days (maximum 8 days) to achieve abstinence and precipitate cannabis withdrawal, after which they were discharged to continue the remaining 3 weeks of treatment as outpatients. The primary endpoints were treatment-related differences in cannabis withdrawal symptoms during hospital admission, and week 4 (end of treatment) self-reported cannabis use and urine THC-COOH concentrations in the intention-to-treat population. The study is registered at ClinicalTrials.gov, number NCT01618656.Between Sept 12, 2012, and Jan 18, 2016, 46 men were randomly assigned to PF-04457845 and 24 to placebo. Adherence to study medication was 88%, as confirmed by video-calling and pill count, and corroborated by corresponding drug and anandamide concentrations in blood. Relative to placebo, treatment with PF-04457845 was associated with reduced symptoms of cannabis withdrawal (first day of treatment mean symptom score 11·00 [95% CI 7·78-15·57] vs 6·04 [4·43-8·24]; difference 4·96 [0·71-9·21]; padj=0·048; second day of treatment 11·74 [8·28-16·66] vs 6·02 [4·28-8·47]; difference 5·73 [1·13-10·32]; padj=0·035) and related mood symptoms during the inpatient phase. Additionally, treatment with PF-04457845 was associated with lower self-reported cannabis use at 4 weeks (mean 1·27 joints per day [95% CI 0·82-1·97] vs 0·40 [0·25-0·62]; difference 0·88 [0·29-1·46]; p=0·0003) and lower urinary THC-COOH concentrations (mean 657·92 ng/mL [95% CI 381·60-1134·30] vs 265·55 [175·60-401·57]; difference 392·37 [17·55-767·18)]; p=0·009). Eight (17%) patients in the PF-04457845 group and four (17%) in the placebo group discontinued during the treatment period. During the 4-week treatment phase, 20 (43%) of 46 participants in the PF-04457845 group and 11 (46%) of 24 participants in the placebo group had an adverse event. There were no serious adverse events.PF-04457845, a novel FAAH inhibitor, reduced cannabis withdrawal symptoms and cannabis use in men, and might represent an effective and safe approach for the treatment of cannabis use disorder.United States National Institute of Drug Abuse (NIDA).

The objective of this paper is to review the available literature regarding the use of cannabis and cannabinoids in adult oncologic pain management.A integrative review was conducted on March 1, 2018 using PubMed, MEDLINE, CINAHL, Embase, and Scopus. A snowball method was used to extract studies included in systematic reviews that were not included in the primary literature search.Articles reviewed address the use of cannabinoids or cannabis for pain management in oncology patients, either as stand- alone or adjuvant therapy.The final number of articles included is nine articles. Of the nine studies reviewed, eight reviewed the effect of the cannabinoid THC on cancer pain, and one study reviewed the use of medicinally available whole plant cannabis. The following study types were included: multiple multi-center, randomized, placebo- controlled trials and two prospective observational survey studies.Of the eight studies that reviewed the effect of the cannabinoid THC, five found THC to be more effective than placebo, one found THC to be more effective than placebo in American patients but ineffective in patients from other countries, and two found THC to be no more effective than placebo. The study that reviewed the effect of the whole plant cannabis found that there was a significant decrease in pain among those patients smoking cannabis.The lack of evidence in this field of research suggests a need to change policy surrounding cannabis research.

Cannabis may be an effective alternative or adjunctive treatment for peripheral neuropathy, an often debilitating condition for which standard treatments often provide little relief. Most studies show moderately improved pain from inhaled cannabis use, but adverse effects such as impaired cognition and respiratory problems are common, especially at high doses. Data on the long-term safety of cannabis treatments are limited. Until risk-benefit profiles are better characterized, doctors in states where cannabis therapy is legal should recommend it for peripheral neuropathy only after careful consideration.

There is strong evidence that plain cigarette packaging and health warning labels (HWLs) reduce brand appeal and increase health knowledge. There is limited evidence examining this population-level public health approach for cannabis packaging. This issue is of particular importance in light of the recent legalization of recreational cannabis in Canada. The current study examined perceptions of plain packaging and HWLs for cannabis packages among young adults.An online experimental study was conducted with a sample of university students in Alberta, Canada (n = 656). Respondents were randomly assigned to view cannabis packages in one of four conditions: Condition 1: branded pack, Condition 2: plain pack (uniform color, brand imagery removed, standardized font), Condition 3: branded pack with a HWL, and Condition 4: plain pack with a HWL. Respondents in Conditions 3 and 4 viewed five text-based HWLs, each corresponding to a health effect associated with cannabis use: (1) brain development, (2) mental health issues, (3) impaired driving, (4) nonlethal overdose, and (5) addiction. After viewing packs, respondents rated packs and health warnings on various measures.Branded packages without HWLs were rated as most appealing compared to all other packs (p < 0.001 for all contrasts). No differences were found in ratings of appeal when comparing branded and plain packs with HWLs. Warning messages for cognitive development and impaired driving were rated highest on levels of perceived effectiveness, believability, and fear, whereas the addiction warning was rated among the lowest. In general, there were gaps in health knowledge related to cannabis use, however after viewing packs with warnings (compared to viewing packs without warnings) levels of health knowledge increased across all health effects (p < 0.01 for all). Lastly, a significant majority of young adults reported they would purchase the branded pack without a HWL (39.5%), compared to all other pack types (p < 0.05 for all contrasts). The lowest proportion of young adults reported they would purchase a plain pack with a HWL (1.1%).Plain packaging and health warnings may reduce brand appeal and increase health knowledge among young adults.

Circadian rhythms have been related to psychiatric diseases and regulation of dopaminergic transmission, especially in substance abusers. The relationship between them remained enigmatic and no data on the role of clock genes on cannabis dependence have been documented. We aimed at exploring the role of clock gene genotypes as potential predisposing factor to cannabis addiction, using a high throughput mass spectrometry methodology that enables the large-scale analysis of the known relevant polymorphisms of the clock genes. We have conducted a case-control study on 177 Caucasians categorizing between cannabis-addicted subjects and casual consumers based on structured interviews recorded socio-demographic data, AUDIT, Fagerström test, MINI, and medical examinations. Alcohol, opiates, and stimulants' consumption was as exclusion criteria. We report an association between several Single Nucleotide Polymorphism (SNP)s in main circadian genes SNPs, especially the gene locus HES7/PER1 on chromosome 17 and cannabis consumption as well as the development of neuropsychiatric and social disorders. This SNP's signature that may represent a meaningful risk factor in the development of cannabis dependence and its severity requires to be deeply explored in a prospective study.

Cancer cachexia (CC) is common in advanced cancer and is accompanied by negative effects on health-related quality of life (HRQOL). However, methods to identify the impact of CC on HRQOL are limited. Single questionnaire items may provide insight on the effect of CC on HRQOL. Specifically, the use of "feeling of wellbeing" (FWB) on the Edmonton Symptom Assessment System (ESAS) questionnaire and the Distress Thermometer (DT) have been explored. Assessing how these two surrogate measures of HRQOL are impacted among CC stages and what drives these negative effects may allow for focused treatments. Five-hundred and twelve patients referred to a Cancer Rehabilitation Program completed the ESAS, with the question on FWB and the DT at baseline. Patients were separated into CC stages: non-cachexia (NC), pre-cachexia (PC), cachexia (C), refractory cachexia (RC). A mixed model ANOVA with post hoc Tukey adjustment was used to compare means of FWB and distress among the CC stages. To understand what was driving the differences between CC stages, a robust regression model was created with either distress or FWB as the outcome measure, dependent on the other measures in ESAS, age and sex. Finally, the use of cannabinoids in treating appetite loss was examined, as it has a detrimental effect on FWB; 54 patients underwent cannabinoid treatment for appetite loss within a community-based, physician-lead, medical cannabis clinic. A t-test to assess changes in ESAS appetite score after 3 months of cannabinoid treatment was examined. RC patients had a significantly poorer sense of wellbeing than the other cachexia stages (RC: 6.07±0.33). Significant differences in distress were identified between RC patients and those with NC and C, but not with PC (RC: 4.87±0.38, NC: 3.35±0.26, PC: 4.11±0.30, C: 3.60±0.28). FWB was negatively affected by worsening appetite in all CC stages except NC (PC: 0.19±0.08, P=0.022; C: 0.26±0.06, P<0.001; RC: 0.23±0.08, P=0.007). ESAS score for lack of appetite significantly improved between baseline (5.07±3.21) and follow-up (3.56±3.15, P=0.003) after cannabinoid treatment, with no significant difference in weight (baseline: 70.7±14.6 kg, 3-month follow-up: 71.0±14.8 kg). Future research should validate both multidimensional and single-item tools to measure HRQOL in patients at different stages of CC. Improvement of HRQOL via appetite stimulation, may be achieved through a multidisciplinary approach, which includes cannabinoid therapy.

Cannabis and tobacco co-use is prevalent, but consensus regarding the reasons for co-use among adults and the degree of interrelatedness between these substances is lacking. Reasons for co-use have been explored with younger users, but little data exists for more experienced users with entrenched patterns of co-use. The goal of this study was to examine characteristics and patterns of cannabis-tobacco co-use among adults in the Southeastern United States (US), where there is a legal landscape of generally restrictive cannabis legislation coupled with more permissive tobacco control compared to other US regions. Participants (N = 432) were regular cannabis users recruited through Amazon Mechanical Turk. Measures included demographics, patterns of cannabis and tobacco use, and reasons for co-use. Within this sample, 42% were current users of tobacco (n = 182). Cannabis-tobacco co-users were older and had more years of cannabis use than cannabis-only users. Among the co-using sub-sample, there was little consistency in the reasons for co-use, suggesting individual differences in the use of both substances. High levels of cannabis-tobacco interrelatedness (i.e., temporally concurrent use) were associated with smoking more cigarettes (tobacco) per day and greater nicotine dependence scores when compared to users with low levels of interrelatedness. Though these results are limited by a small sample size and generalizability issues, there were individual differences in cannabis-tobacco relatedness, which may be of importance when considering treatment strategies for cannabis, tobacco, or both. With additional research, personalized strategies adapted to cannabis-tobacco relatedness profiles among co-users may be warranted as a treatment strategy.

Numerous preclinical studies show that acute cannabinoid administration impairs cognitive performance. Almost all of this research has employed cannabinoid injections, however, whereas smoking is the preferred route of cannabis administration in humans. The goal of these experiments was to systematically determine how acute exposure to cannabis smoke affects working memory performance in a rat model. Adult male (n = 15) and female (n = 16) Long-Evans rats were trained in a food-motivated delayed response working memory task. Prior to test sessions, rats were exposed to smoke generated by burning different numbers of cannabis or placebo cigarettes, using a within-subjects design. Exposure to cannabis smoke had no effect on male rats' performance, but surprisingly, enhanced working memory accuracy in females, which tended to perform less accurately than males under baseline conditions. In addition, cannabis smoke enhanced working memory accuracy in a subgroup of male rats that performed comparably to the worst-performing females. Exposure to placebo smoke had no effect on performance, suggesting that the cannabinoid content of cannabis smoke was critical for its effects on working memory. Follow-up experiments showed that acute administration of either Δ9-tetrahydrocannabinol (0.0, 0.3, 1.0, 3.0 mg/kg) or the cannabinoid receptor type 1 antagonist rimonabant (0.0, 0.2, 0.6, 2.0 mg/kg) impaired working memory performance. These results indicate that differences in the route, timing, or dose of cannabinoid administration can yield distinct cognitive outcomes, and highlight the need for further investigation of this topic.

Cannabis is the most widely used illicit drugs and the changing legal, political and cultural climate will likely increase cannabis use further. One factor that may underlie the transition from recreational use to problematic use is stress. The hormone oxytocin (OXT) modulates stress and may have therapeutic efficacy for substance use disorders, but few studies have examined OXT in cannabis users. Another factor is sex; although more men smoke cannabis, the transition from recreational to problematic use is faster in women. Using a within-subjects design, the effects of intranasal (i.n.) oxytocin (OXT; 40 IU) administration on stress reactivity (using the Trier Social Stress Test; TSST) and cannabis (5.6% THC) self-administration was assessed in recreational cannabis using men (n = 31) and women (n = 32) relative to i.n. placebo (PBO) and no-stress (NST) conditions. The TSST produced expected subjective and cardiovascular effects compared to the NST. However, in the i.n. OXT-TSST condition, positive subjective effects were lower and negative subjective effects were higher in women compared to PBO administration and compared to men. Further, latency to self-administer cannabis was longer in women than men and women self-administered less cannabis than men regardless of stress condition. There were no differences in cannabis craving as a function of sex, stress, or medication. These results suggest that OXT administration may lead to greater stress reactivity in recreational cannabis users, particularly women, and support growing evidence that sex differences should be carefully considered when examining the therapeutic potential of OXT.

Little is known about the reproductive effects of paternal cannabis exposure. We evaluated associations between cannabis or tetrahydrocannabinol (THC) exposure and altered DNA methylation in sperm from humans and rats, respectively. DNA methylation, measured by reduced representation bisulfite sequencing, differed in the sperm of human users from non-users by at least 10% at 3,979 CpG sites. Pathway analyses indicated Hippo Signaling and Pathways in Cancer as enriched with altered genes (Bonferroni p < 0.02). These same two pathways were also enriched with genes having altered methylation in sperm from THC-exposed versus vehicle-exposed rats (p < 0.01). Data validity is supported by significant correlations between THC exposure levels in humans and methylation for 177 genes, and substantial overlap in THC target genes in rat sperm (this study) and genes previously reported as having altered methylation in the brain of rat offspring born to parents both exposed to THC during adolescence. In humans, cannabis use was also associated with significantly lower sperm concentration. Findings point to possible pre-conception paternal reproductive risks associated with cannabis use.

A sensitive, robust method was developed and validated to quantitate thirteen major natural cannabinoid parent and metabolite compounds in human plasma at or below 0.5 ng/mL.A liquid chromatography-tandem mass spectrometry method was developed and validated to measure thirteen cannabinoid compounds: cannabidiol (CBD), cannabidiolic acid (CBDA), cannabidivarin (CBDV), cannabinol (CBN), cannabigerol (CBG), cannabigerolic acid (CBGA), cannabichromene (CBC), Δ-tetrahydocannabinol (THC), Δ-tetrahydrocannabinolic acid A (THCA), Δ-tetrahydrocannabivarin (THCV), 11-hydroxy-Δ-tetrahydrocannbinol (11-OH-THC), 11-nor-9-carboxy-Δ-tetrahydrocannbinol (THC-COOH), and 11-nor-9-carboxy-Δ-tetrahydrocannabinol-glucuronide (THC-COOH-glu). Samples (200 µL) were extracted via protein precipitation and separated with a Kinetex-EVO C18 column and a 65%-95% gradient of methanol and 0.2% ammonium hydroxide/H2O at a flow rate of 0.4 mL/min. Samples were obtained from patients with epilepsy receiving cannabis for the treatment of seizures.The extracted lower limit of quantification was 0.05 ng/mL for CBD, CBDV, CBN, and 11-OH-THC; 0.10 ng/mL for CBDA, CBG, CBC, CBGA, THC, THCA, and THCV; 0.50 ng/mL for THC-COOH and THC-COOH-glu. Mean QC intra-day accuracy and precision for all analytes ranged 96.5-104% and 2.7-4.9% respectively while inter-day accuracy and precision ranged 98-103.3% and 0.2-3.6%, respectively. An absolute matrix effect was observed for some analytes, however, with minimal relative matrix effect. Lack of nonspecific drug binding to extraction glass and plasticware was verified. Patient CBD levels ranged from 0.135-11.13 ng/mL.The validated method met FDA guidelines for Bioanalytical Assays precision and accuracy criteria. The assay reliably confirmed the use of particular medical cannabis formulations in patient samples as well as reliably measured low CBD concentrations from single dose CBD exposure.

Previous research has demonstrated that externalizing symptoms, cannabis use problems, and poor decision-making abilities are each independently related to risky sexual behavior (RSB). However, few studies have examined the joint effect of these factors on RSB among a sample of adolescents.The current study addresses this gap in the literature by examining how externalizing disorder symptoms, cannabis use, and decision-making abilities interact to predict RSB among a sample of adolescents (n = 204; Mage = 15.5) at-risk for escalation in cannabis use. Poisson regression was used for all analyses, and simple slope difference tests were used for all post-hoc analyses.A greater number of externalizing symptoms, more problems from cannabis use, and more risk disadvantageous choices on the Cups Task (CT) total trials and more risk disadvantageous choices on the CT-gain trials predicted greater RSB endorsement. Findings also highlight significant interactions between cannabis use problems and CT-total and -gain trial performance, as well as between cannabis use problems and externalizing symptoms in predicting RSB.Current treatment and prevention approaches to reduce RSB among adolescents may benefit from incorporating techniques that improve decision-making skills.

Background: Considering the enormous progress in the field of neuropharmacology and its global importance, as well as the lack of bibliometric studies examining this field as a whole, it is a high time to assess the prevailing topics and citation performances of its research works. Methods: Web of Science (WoS) was searched to identify relevant neuropharmacology articles, which were analyzed with reference to (1) publication year, (2) journal title, (3) total citation count, (4) authorship, (5) WoS category, and (6) manuscript type. The identified manuscripts were analyzed with VOSviewer for further bibliometric parameters, such as citation analysis of institutions, countries/regions, and journals, and to visualize the citation patterns of the terms appearing in the titles and abstracts. Results: The literature search resulted in 43,354 manuscripts. Nearly 98% of them were published since the 1990s. The majority of the manuscripts were original articles (n = 31,360) and reviews (n = 11,266). The top five WoS categories associated with the analyzed manuscripts were Pharmacology/Pharmacy (n = 14,892, 34.3%), Neurosciences (n = 11,747, 27.1%), Clinical Neurology (n = 4,981, 11.5%), Psychiatry (n = 4,464, 10.3%), and Biochemistry/Molecular Biology (n = 4,337, 10.0%). Seven of the top ten most prolific institutions were located in the USA, and one each in Canada, Italy, and the UK, respectively. Manuscripts mentioning certain molecules or pharmaceuticals had high citations per manuscript, such as those reporting about anandamide, tetrahydrocannabinol (THC), L-glutamate, clozapine, and curcumin. These terms with at least 50 citations per manuscript were mostly related to cannabis and anti-psychotic drugs, with some dealing with anti-epilepsy effects and Alzheimer's disease. Conclusion: We have identified and analyzed all neuropharmacology articles published since the 1990s. Importantly, the area of neuropharmacology research has been growing steadily due to the global trend in population aging and associated with this continuously increasing number of patients with neuropsychiatric disorders worldwide. It is hoped that identification of new pharmaceutically useful molecules or new clinical applications will continue in the future, in order to improve clinical outcomes and to further strengthen the field of neuropharmacology, a research area cross-linking basic and clinical sciences.

Methylphenidate (MPH) is a first line treatment for ADHD and is also misused as a purported cognitive enhancer, yet its effects on brain function are still poorly understood. Recent functional magnetic resonance imaging (fMRI) studies showed that MPH altered cortico-striatal resting functional connectivity (RFC). Here we investigated the effects of MPH in thalamic connectivity since the thalamus modulates striato-cortical signaling. We hypothesized that MPH would increase thalamic connectivity and metabolism, and that this response would be blunted in cannabis abusers. For this purpose, we measured RFC in seven thalamic nuclei using fMRI and brain glucose metabolism using positron emission tomography (PET) and 18F-fluorodeoxyglucose (FDG) in sixteen healthy controls and thirteen participants with cannabis use disorder (CUD) twice after placebo and after MPH (0.5 mg/kg, iv). MPH significantly increased thalamo-cerebellar connectivity and cerebellar metabolism to the same extent in both groups. Group comparisons revealed that in CUD compared to controls, metabolism in nucleus accumbens was lower for the placebo and MPH measures, that MPH-induced increases in thalamic metabolism were blunted, and that enhanced negative connectivity between thalamus and accumbens in CUD was normalized by MPH (reducing negative connectivity). Our findings identify the thalamus as a target of MPH, which increased its metabolism and connectivity. The reduced metabolism in nucleus accumbens and the disrupted thalamo-accumbens connectivity (enhanced negative connectivity) in CUD is consistent with impaired reactivity of the brain reward's circuit. MPH's normalization of thalamo-accumbens connectivity (reduced negative connectivity) brings forth its potential therapeutic value in CUD, which merits investigation.

The emergence of synthetic cannabinoids (SCBs) as drugs of abuse in readily available "Spice" smoking blends has exposed users to much more potent cannabinoids than the phytocannabinoids present in Cannabis sativa L. Increasing reports of adverse reactions are emerging in the clinical literature. SCBs may disrupt the endocannabinoid signalling, which has been shown to be crucial within human endometrium remodelling process. Within this study, a telomerase-immortalised human endometrial stromal cell line (St-T1b) and primary human decidual fibroblasts (HdF) were used to determine the impact of SCBs JWH-122, UR-144 and WIN55,212-2 (WIN) on endometrial stromal cells. Our findings indicate that JWH-122 and UR-144 (0.01-25 μM) induce prompt ROS/RNS formation and endoplasmic reticulum (ER) stress without reduction in cell viability. Disturbances in the normal functions of the ER lead to cell stress response, which is after compensated with the increase in reduced/oxidized glutathione ratio (GSH/GSSG). Instead, WIN induces ER stress, mitochondrial dysfunction and apoptotic cell death. The addition of the CB1 antagonist AM281 significantly reduces the effects on cell viability, suggesting that CB1 plays a key role in WIN-induced apoptosis. Collectively, our data suggests that SCBs have dissimilar effects on human endometrial stromal cells and, thus, may impact human reproductive function through distinct mechanisms that are crucial for the understanding of the pathophysiological outcomes from its abuse.

Background: People who abuse substances are at increased risk of metabolic syndrome and diabetes resulting partly from increased cell damage and due to the effects of opioids on glucose homeostasis. Therefore, people with diabetes who abuse substances may carry greater health risks than the general population resulting from their effect on glucose metabolism. These substances may be in the form of cannabis, hallucinogens, opioids, and stimulants. Therefore, the aim of this review was to evaluate the effects of substance abuse on blood glucose parameters in patients with diabetes. Method: Databases including Embase, Psycho-Info, Google Scholar and PubMed were searched systematically for relevant articles from database inception to May 2018. Search terms including medical subject headings (MeSH) based on the Population, Intervention, Comparator and Outcomes (PICO) framework was used to access the databases. Eligible articles were selected based on set inclusion and exclusion criteria. The articles reviewed were evaluated for quality and meta-analysis and sensitivity analysis were carried out using the Review Manager (RevMan 5.3, The Cochrane Collaboration, Copenhagen, Denmark). The Random effects model was used for the data analysis. Results: Twelve studies which met the inclusion criteria were included in the systematic review, while nine articles were selected for the meta-analysis. The results of the meta-analysis showed that substance abuse does not have significant effects (p > 0.05) on postprandial blood glucose and glycated haemoglobin in patients with diabetes. With respect to the effect of substance abuse on fasting blood glucose, while this was significant (p < 0.05) following meta-analysis, the results of the sensitivity test did not demonstrate any significant difference (p > 0.05) between patients who abused substances compared with control. This would suggest that the effect of substance abuse on fasting blood glucose in these patients was not very reliable or not consistent. Conclusions: The effect of substance abuse on glycated haemoglobin and postprandial blood glucose in patients with diabetes was not significant. In the meta-analysis, while the value was slightly lower with respect to postprandial blood glucose, this was slightly higher in relation to HbA1c in the substance abuse group compared with control. On the other hand, the effect of substance abuse on fasting blood glucose was significant (p = 0.03) compared with control, but this was attenuated following a sensitivity test. A range of factors including eating habits, characteristics of drugs, erratic lifestyle of patients may explain the outcome of this review. There is the need for randomised controlled trials that will include diet and medication history in order to fully understand the effect of substance abuse on blood glucose parameters in patients with diabetes.

Cannabinoids have demonstrated utility in the management of cancer, obesity, and neurologic disease. More recently, their immunosuppressive and anti-inflammatory properties have been identified for the treatment of several dermatologic conditions. This review thus assesses the therapeutic potential of phytocannabinoids, endoocannabinoids, and chemically synthetic cannabinoids in the management of cutaneous disease. The PubMed® and Scopus® databases were subsequently reviewed in December 2017 using MeSH and keywords, such as cannabinoid, THC, dermatitis, pruritus, and skin cancer. The search yielded reports on the therapeutic role of cannabinoids in the management of skin cancer, acne vulgaris, pruritus, atopic and allergic contact dermatitis, and systemic sclerosis. While cannabinoids have exhibited efficacy in the treatment of inflammatory and neoplastic skin conditions, several reports suggest pro-inflammatory and pro-neoplastic properties. Further investigation is necessary to understand the complexities of cannabinoids and their therapeutic potential in dermatology.

Policing practices do not reflect recent decriminalization of drug possession in Mexico. We assessed knowledge of cannabis law as part of a police education program (PEP) post-drug law reform in Tijuana.Officers took pre-/post-PEP surveys; random subsample (n = 759) received follow-up assessments. Longitudinal logistic regression (pre-, post-, 3-months post-PEP) measured knowledge of cannabis law.PEP increased conceptual knowledge of cannabis law from baseline to post-training (AOR = 56.1, CI: 41.0-76.8) and 3 months post-PEP (AOR = 11.3, CI: 9.0-14.2).PEPs improve police knowledge of cannabis law. Reforms should be bundled with PEPs to improve policy implementation. (Am J Addict 2018;XX:XX-XX).

To assess the benefits and harms of cannabis-based products for pediatric epilepsy.We identified in this living systematic review randomized controlled trials (RCTs) and nonrandomized studies (NRSs) involving children with epilepsy treated with cannabis-based products. We searched MEDLINE, Embase, PsycINFO, Cochrane Library, and gray literature (April 25, 2018). The primary outcome was seizure freedom; secondary outcomes were seizure frequency (total, ≥50% reduction), quality of life, sleep, status epilepticus, death, gastrointestinal adverse events, and visits to the emergency room. Data were pooled by random-effects meta-analysis. Risk of bias was assessed for each study, and GRADE was used to assess the quality of evidence for each outcome.Four RCTs and 19 NRSs were included, primarily involving cannabidiol. All RCTs were at low risk of bias, whereas all NRSs were at high risk. Among RCTs, there was no statistically significant difference between cannabidiol and placebo in seizure freedom (relative risk [RR] = 6.77, 95% confidence interval [CI] = 0.36-128.38; 1 RCT), quality of life (mean difference = 0.6, 95% CI = -2.6 to 3.9; 3 RCTs), sleep disruption (mean difference = -0.3, 95% CI = -0.8 to 0.2; 3 RCTs), or vomiting (RR = 1.00, 95% CI = 0.51-1.96; 4 RCTs). There was a statistically significant reduction in the median frequency of monthly seizures with cannabidiol compared with placebo (-19.8%, 95% CI = -27.0% to -12.6%; 3 RCTs) and an increase in the number of participants with at least a 50% reduction in seizures (RR = 1.76, 95% CI = 1.07-2.88; 1 RCT) and diarrhea (RR = 2.25, 95% CI = 1.38-3.68; 3 RCTs). Death and status epilepticus were infrequently reported.Evidence from high-quality RCTs suggests that cannabidiol probably reduces seizures among children with drug-resistant epilepsy (moderate certainty). At this time, the evidence base is primarily limited to cannabidiol, and these findings should not be extended to all cannabis-based products.

Introduction: Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are bioactive cannabinoids. We recently showed that acute THC administration drives region-dependent changes in the mouse brain lipidome. This study tested the hypothesis that cell lines representing cell types present in the central nervous system (CNS), neurons (N18 cells), astrocytes (C6 glioma cells), and microglia (BV2 cells) would respond differently to THC, CBD, or their combination. This experimental strategy also allowed us to test the hypothesis that THC and CBD are metabolized differently if presented in combination and to test the hypothesis that responses to CBD are not like the fatty acid amide hydrolase (FAAH) inhibitor URB597. Finally, we tested the hypothesis that CBD's CNS effects would differ in the N-acyl phosphatidyl ethanolamine-specific phospholipase D (NAPE-PLD) knockout (KO) compared to wild-type (WT) mice. Methods: N18, C6, and BV2 cells were stimulated with 1 μM THC, 1 μM CBD, 1 μM THC:CBD, 1 μM URB597, or vehicle for 2 h and lipids extracted. Adult female WT and NAPE-PLD KO mice were injected with 3 mg/kg CBD or vehicle i.p., brains collected 2 h later, eight brain regions dissected, and lipids extracted. Extracted lipids were characterized and quantified using high-pressure liquid chromatography coupled with tandem mass spectrometry (HPLC/MS/MS). Results: Lipid levels in each cell type were differentially affected by THC, CBD, or THC:CBD with a few exceptions. In all cell lines, THC increased levels of arachidonic acid and CBD increased levels of N-acyl ethanolamines (NAEs), including N-arachidonoyl ethanolamine. More THC remained when cells were coincubated with CBD; however, levels of THC metabolites were cell-type dependent. CBD and URB597 caused very different lipid profiles in the cell-based assays with the primary similarity being increases in NAEs. CBD increased levels of NAEs in the WT hippocampus, cerebellum, thalamus, cortex, midbrain, and brainstem; however, NAEs did not increase in any brain region after CBD in NAPE-PLD KO mice. Conclusions: CBD and THC differentially modify the lipidome of the brain and CNS-type cell lines. Increases in NAEs observed after CBD treatment had previously been attributed to FAAH inhibition; however, data here suggest the alternative hypothesis that CBD is activating NAPE-PLD to increase NAE levels.

There has been emerging evidence of an association between tobacco smoking and schizophrenia spectrum disorders (SSD). Two meta-analyses have reported that people who smoke tobacco have an ~2-fold increased risk of incident schizophrenia or psychosis, even after adjusting for confounding factors. This study aimed to critically appraise the research which has examined the association between tobacco smoking and SSD against the Bradford Hill criteria for causality, to determine the strength of the evidence for a causal relationship. Eight longitudinal studies (seven cohort studies and one case control study) were identified which examined tobacco smoking as an exposure and psychosis as an outcome. All seven cohort studies were assessed as being of high quality using the Newcastle-Ottawa Scale. Six of the eight studies found a statistically significant positive association between tobacco smoking and onset of SSD. These studies reported a consistent association with a moderate to large effect size and a dose response relationship. The studies adjusted for multiple potential confounders including age, sex, socioeconomic status, shared genetic risk, prodromal symptoms, and comorbid cannabis and other substance use. The studies did not adjust for exposure to childhood trauma or prenatal tobacco. There was substantial though inconclusive evidence supporting a causal relationship between tobacco smoking and increased risk of SSD. If a causal relationship does exist, nicotine is most likely responsible for this association. This raises serious public health concerns about the increasing use of e-cigarettes and other products, particularly by adolescents whose nicotine use may increase their risk of SSD. Research is urgently needed to examine the association between e-cigarette use and incident psychosis, particularly in adolescents and young adults.

The endocannabinoid system (ECS) has been recently recognized as a prominent promoter of the emotional homeostasis, mediating the effects of different environmental signals including rewarding and stressing stimuli. The ECS modulates the rewarding effects of environmental stimuli, influencing synaptic transmission in the dopaminergic projections to the limbic system, and mediates the neurophysiological and behavioral consequences of stress. Notably, the individual psychosocial context is another key element modulating the activity of the ECS. Finally, inflammation represents an additional factor that could alter the cannabinoid signaling in the CNS inducing a "sickness behavior," characterized by anxiety, anhedonia, and depressive symptoms. The complex influences of the ECS on both the environmental and internal stimuli processing, make the cannabinoid-based drugs an appealing option to treat different psychiatric conditions. Although ample experimental evidence shows beneficial effects of ECS modulation on mood, scarce clinical indication limits the use of cannabis-based treatments. To better define the possible clinical indications of cannabinoid-based drugs in psychiatry, a number of issues should be better addressed, including genetic variability and psychosocial factors possibly affecting the individual response. In particular, better knowledge of the multifaceted effects of cannabinoids could help to understand how to boost their therapeutic use in anxiety and depression treatment.

In recent years, drug prevention networks and drug education programs have started using Web-based or mobile phone apps as novel prevention tools, testing their efficacy compared with face-to-face prevention.The aim of this study was to assess the potential of an interactive app called Once Upon a High (VoltEgySzer).The app approaches drug prevention from 6 different aspects, and it addresses youngsters with 6 different modules: (1) interactive comics/cartoons, telling stories of recovery; (2) quiz game; (3) roleplay game; (4) introduction of psychoactive drugs; (5) information on the somatic and psychological effects of psychoactive substances; (6) list of available treatment units, rehabs, and self-support groups in Hungary. Students of 2 vocational schools and 2 high schools filled out a questionnaire at a baseline (T0) and a 2-month follow-up (T1) data collection session. Students of 1 vocational school and 1 high school downloaded the Once Upon a High app (app group), whereas students from the other vocational school and high school did not (nonapp group). The time points of T0 and T1 questionnaires contained demographic variables, items with regard to substance use characteristics for both legal and illegal substances, including novel psychoactive substance, exercise habits, knowledge about psychoactive substances, attitudes toward substance users and validated instruments measuring the severity of tobacco (Fagerström Test for Nicotine Dependence), alcohol (Alcohol Use Disorder Identification Test), cannabis (Cannabis Abuse Screening Test), and synthetic cannabinoid consumption. Beliefs about substance use (Beliefs About Substance Abuse) and perceived self-efficacy (General Perceived Self-Efficacy) were also measured. At T1, members of the app group provided additional evaluation of the app.There were 386 students who participated in the T0 session. After dropout, 246 students took part in T1 data collection procedure. Alcohol was the most frequently consumed psychoactive substance (334/364, 91.8% lifetime use), followed by tobacco (252/386, 65.3%, lifetime use) and cannabis (43/323, 13.3% lifetime use). Decreased self-efficacy (beta=-.29, P=.04) and increased daily physical exercise frequencies (beta=.04, P<.001) predicted higher frequencies of past month energy drink consumption, whereas elevated past month alcohol consumption was mainly predicted by a decrease in negative attitudes toward substance users (beta=-.13, P=.04) in the regression models. Once Upon a High was found to be effective only in reducing energy drink consumption (beta=-1.13, P=.04) after controlling for design effect, whereas perceived utility of the app showed correlation with a decreasing alcohol use (rS(44)=.32, P=.03). The roleplay module of the app was found to be the most preferred aspect of the app by the respondents.The Once Upon a High app can be a useful tool to assist preventive intervention programs by increasing knowledge and self-efficacy; however, its efficacy in reducing or preventing substance use needs to be improved and further studied. Additional potential impacts of the app need further testing.

Wastewater-based epidemiology is a well-established and complementary approach for monitoring illicit drug use in the general population. In this study, amphetamine (AMP), methamphetamine (METH), 3,4-methylenedioxymethamphetamine (MDMA), cocaine (COC) (from benzoylecgonine), and cannabis (from THC-COOH) consumption levels were investigated for the first time in Turkey (Istanbul). A solid-phase extraction method was applied to influent wastewater samples collected from two districts, Beyoglu and Catalca. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis was conducted with electrospray ionization in positive mode. Calibration curves were acquired in linear form with >0.999 correlation coefficients. Limit of detection levels were measured as 0.91-151 ng/L, and limit of quantitation levels were in the range of 3 to 500 ng/L. Solid-phase extraction recovery and repeatability experiments were achieved by spiking the mix solution to different concentrations (50, 250, 750 ng/L) in 50 mL tap water and wastewater (500, 1000 ng/L) samples in six replicates. The method was optimized, and recoveries were found to be over 80% for all six substances with up to 11.9% relative standard deviation. According to the real sample results, cannabis was found to be the most abused illicit substance among the analytes. The mean consumptions of the two districts, including seven consecutive days for AMP, METH, MDMA, COC, and cannabis, were found to be 27.2, 322, 331, 385, and 1224 mg/day/1000 inhabitants, respectively. In this presented study, all targeted compounds were analyzed simultaneously with the same analytical conditions. To the best of our knowledge, this report is the first to present illicit drug consumption data from Istanbul.

Current data suggest that opioid misuse or opioid use disorder (OUD) may be over represented among tobacco users. However, this association remains understudied in primary care settings. A better understanding of the extent of heterogeneity in opioid misuse among primary care patients who use tobacco may have implications for improved primary care-based screening, prevention, and intervention approaches.Data were derived from a sample of 2000 adult (aged ≥18) primary care patients across 5 distinct clinics. Among past-year tobacco users (n = 882), we assessed the prevalence of opioid misuse and OUD by sociodemographic characteristics and past-year polysubstance use. Latent class analysis (LCA) was used to identify heterogeneous subgroups of tobacco users according to past-year polysubstance use patterns. Multinomial logistic regression was used to examine variables associated with LCA-defined class membership.Past-year tobacco use was reported by >84% of participants who reported past-year opioid misuse or OUD. Among those reporting past-year tobacco use, the prevalence of past-year opioid misuse and OUD was 14.0% and 9.5%, respectively. The prevalence of opioid misuse or OUD was highest among tobacco users who were male or unemployed. Three LCA-defined classes among tobacco users were identified including a tobacco-minimal drug use group (78.0%), a tobacco-cannabis use group (10.1%), and a tobacco-opioid/polydrug use group (11.9%). Class membership differed by sociodemographic characteristics.Results from this study support the benefit of more comprehensive assessment of and/or monitoring for opioid misuse among primary care patients who use tobacco, particularly for those who are male, unemployed, or polydrug users.

Prescription opioid misuse in Canada has become a serious public health concern and has contributed to Canada's opioid crisis. There are thousands of Canadians who are currently receiving treatment for opioid use disorder, which is a chronic relapsing disorder with enormous impact on individuals and society.The aim of this study was to compare the clinical and demographic differences between cohorts of patients who were introduced to opioids through a prescription and those introduced to opioids for non-medical purposes.This was an observational, prospective cohort study.The study took place in 19 Canadian Addiction Treatment Centres across Ontario.We included a total of 976 participants who were diagnosed with Opioid Use Disorder and currently receiving methadone maintenance treatment. We excluded participants who were on any other type of prescription opioid or who were missing their 6-month follow-up urine screens. We measured the participants' initial source of introduction to opioids along with other variables using the Maudsley Addiction Profile. We also measured illicit opioid use using urine screens at baseline and at 6-months follow-up.Almost half the sample (n = 469) were initiated to opioids via prescription. Women were more likely to be initiated to opioids via a prescription (OR = 1.385, 95% CI 1.027-1.866, P = .033). Those initiated via prescription were also more likely to have post-secondary education, older age of onset of opioid use, less likely to have hepatitis C and less likely to have use cannabis. Chronic pain was significantly associated with initiation to opioids through prescription (OR = 2.720, 95% CI 1.998-3.722, P < .0001). Analyses by gender revealed that men initiated by prescription were less likely to have liver disease and less likely to use cannabis, while women initiated by prescription had a higher methadone dose.This project was limited by its study design being observational in nature; no causal relationships can be inferred. Also, the data did not allow determination of the role that the prescribed opioids played in developing opioid use disorder.Our results have revealed that almost half of this methadone maintenance treatment (MMT) population has been introduced to opioids through a prescription. Given that the increasing prescribing rates of opioids has an impact on this at-risk population, alternative treatments for pain should be considered to help decrease this opioid epidemic in Canada.Opioid use disorder, chronic pain relief, methadone maintenance treatment, prescriptions, male, female.

Studies suggest cannabis may improve symptoms like pain and muscle spasticity in patients with multiple sclerosis (PwMS). Despite cannabis' new-found legality and availability, few studies have explored the profile of PwMS cannabis users and characteristics of their use, particularly in a state where cannabis is legal both for recreational and medicinal use. The purpose of the current study was to evaluate cannabis use among PwMS at a large academic multiple sclerosis (MS) clinic, specifically: (1) prevalence, (2) products used (e.g., cannabidiol vs Δ9-tetrahydocannabinol), (3) symptom treatment, and (4) patient characteristics.PwMS completed questions assessing personal opinions about cannabis use, characteristics of cannabis use, MS history, and sociodemographic details, as well as the self-reported disability-Patient Determined Disease Steps (PDDS), overall quality of life-the Patient Reported Outcome Measure Information System (PROMIS-10), and cognition-the Neuro-QoL ACGC v1.0 measures.Thirty-eight percent (n = 96) of PwMS were current Cannabis users (CUs). Although there were no sociodemographic or clinical differences (p ≤ 0.05) between CUs and Non-Cannabis users (NUs), CUs had significantly higher median disability compared to NUs (PDDS = 2 vs. 1; p = 0.02). Among CUs, 57% categorized their use as strictly medicinal. CUs reported using cannabis most often for pain and insomnia/poor sleep and experienced greater than 60% benefit/relief from cannabis use. Over 90% of respondents desire more research on cannabis for MS, and 74% indicated they would consider using cannabis for their MS.As cannabis legalization has impacted the variety of cannabis products available, there appears to be growing numbers of PwMS using cannabis, with this study's CUs reporting use of highly efficacious products with minimal side-effects.

Growing evidence shows cannabis use is associated with lower rates of metabolic dysregulation. Despite cannabis impacting each sex differently, few studies have examined the metabolic profile of male and female cannabis users separately. Our aim was to investigate sex differences in the impact of cannabis use on metabolic syndrome in adults with psychotic illness.Data from 1078 men and 735 women interviewed in the second Australian national survey of psychosis were analyzed using multiple logistic regression to model separately, for each sex, the influence of no, occasional and frequent past-year cannabis use on metabolic syndrome, adjusting for potential covariates including antipsychotic medication, smoking, and physical activity.The proportion of women and men with metabolic syndrome was 58.1% and 57.6% respectively. Unadjusted analyses showed frequent cannabis use was associated with significantly lower odds of metabolic syndrome for both sexes. In adjusted analyses, the association between metabolic syndrome and frequent cannabis use remained significant for men (AOR = 0.49, 95% CI = 0.31-0.78), but not for women (AOR = 0.68, 95% CI = 0.37-1.24). Frequent cannabis use was associated with lower odds of abdominal obesity, hypertension and elevated triglyceride levels in men only.The differences we found suggest cannabinoid regulation of energy balance may be sex-dependent and highlight the importance of examining cannabis use in men and women separately. At the same time, the negative association between cannabis and psychosis onset and relapse should not be dismissed.

English national prospective, observational cohort study of patients continuously enrolled for five years in opioid substitution treatment (OST) with oral methadone and sublingual buprenorphine. This is a secondary outcome analysis of change in use of alcohol and other drug use (AOD) following identification of heroin use trajectories during OST.All adults admitted to community OST in 2008/09 and enrolled to 2013/14 (n = 7717). Data from 11 sequential, six-monthly clinical reviews were used to identify heroin and AOD use trajectories by multi-level Latent Class Growth Analysis. OST outcome in the sixth and seventh year was 'successful completion and no re-presentation' (SCNR) to structured treatment and was assessed using multi-level logistic regression.With 'rapid decreasing' heroin use trajectory as referent, 'continued high-level' heroin use predicted 'continued high-level' crack cocaine use (relative risk ratio [RRR] 58.7; 95% confidence interval [CI] 34.2-100.5),'continued high-level' alcohol use (RRR 1.2; 95% CI 1.0-1.5), 'increasing' unspecified drug use (RRR 1.7; 95% CI 1.4-2.1) and less 'high and increasing' cannabis use (RRR 0.5; 95% CI 0.4-0.6). 'Increasing' crack use was negatively associated with SCNR outcome for the 'decreasing then increasing' and 'gradual decreasing' heroin use groups (adjusted odds ratio [AOR] 0.5; 95% CI 0.3-0.9 and AOR 0.2; 95% CI 0.1-0.7, respectively).Continued high-level heroin use non-response during long-term OST is associated with high-level crack cocaine and alcohol use, increasing unspecified drug use, but less high and increasing cannabis use. Increasing use of crack cocaine is negatively associated with the likelihood that long-term OST is completed successfully.

To describe patterns of cannabis withdrawal among a large sample of those who use medical cannabis and test the association between withdrawal symptomology and functioning.Adults ages 21 and older (N = 801) who were seeking medical cannabis certification (either for the first time or as a renewal) for chronic pain at medical cannabis clinics in southern Michigan completed baseline measures of cannabis use, withdrawal symptomology, functioning and other related constructs. Patients were included in the current study if they endorsed using cannabis at least weekly over the past three months. Of the persons in the baseline sample (N = 801), 83% endorsed using cannabis at this level of frequency and duration (N = 665).Approximately two-thirds of the sample (67.8%) reported at least one moderate or severe withdrawal symptom. The most commonly observed symptom was sleep difficulties (50.3%), followed by anxiety (27.8%), irritability (26.7%), and appetite disturbance (25.2%). Patients with low mental functioning had significantly higher rates of withdrawal symptom endorsement than patients with high mental functioning. However, no association was observed between physical functioning and withdrawal symptom endorsement. These patterns of association were consistent in multivariate analyses that controlled for other potentially confounding variables.Cannabis withdrawal symptomology is highly prevalent among patients who use medical cannabis at least three times a week. Helping patients recognize the association between poorer functioning and withdrawal may be an effective way to highlight potentially negative consequences of regular and moderate heavy use.

Three new stilbenoids (1-3) and 16 known stilbenoids (4-6) and cannabinoids (7-19) were isolated from the leaves of hemp (Cannabis sativa L.). The structures of the three new compounds were identified as α,α'-dihydro-3',4,5'-trihydroxy-4'-methoxy-3-isopentenylstilbene (HM1), α,α'-dihydro-3,4',5-trihydroxy-4-methoxy-2,6-diisopentenylstilbene (HM2), and α,α'-dihydro-3',4,5'-trihydroxy-4'-methoxy-2',3-diisopentenylstilbene (HM3) by 1D and 2D NMR spectroscopy, LC-MS, and HRESIMS. The known α,α'-dihydro-3,4',5-trihydroxy-4,5'-diisopentenylstilbene (5) and combretastatin B-2 (6) were isolated for the first time from C. sativa f. sativa. These isolated compounds exhibited cytotoxic effects on human cancer cells via inhibiting the proliferation of cancer cells and inducing cell death. Among them, compounds 4, 5, 10, 12, 13, 15, and 19 displayed broad-spectrum cytotoxicity, and 1, 7, and 11 displayed selectivity in inhibition efficiency on MCF-7 and A549 cells, which suppressed the proliferation of cancer cells significantly by inducing cell death. The effects of compounds 1-3 on improving reverse cholesterol transport (RCT) were evaluated by isotope-tracing and western blotting. Results showed that the three stilbenoids showed a cytotoxicity above 1.0 mg L-1, especially that of HM3. They could improve [3H]-cholesterol efflux from Raw 264.7 macrophages to high density lipoproteins by enhancing the protein expression of ABCG1 and SR-B1, and HM1 and HM2 showed a significant difference compared with fenofibrate at 1.0 mg L-1. The three stilbenoids could also significantly improve the protein expression of ABCA1. Further study on HepG2 cells indicated that they improve the protein expression of LDLR, SR-B1 and CYP7A1, especially that of HM1 and HM3. However, they showed no significant effect on PCSK9. The above results indicated that these stilbenoids may elevate the transfer of cholesterol to hepatocytes by improving the protein expression of SR-B1 and LDLR, and the synthesis of bile acid by increasing the protein expression of CYP7A1. In conclusion, HM1 showed lower cytotoxicity and higher activity in improving the RCT-related protein expression. Our study suggests that it may be explored as a novel lipid-lowering drug and as a beneficial ingredient in health functional foods and pharmaceuticals.

Background: The emergence of a multidrug-resistant strain of Plasmodium falciparum (Pf Pailin) raises concern about malaria control strategies. Unfortunately, the role(s) of natural plants/remedies in curtailing malaria catastrophe remains uncertain. The claims of potential antimalarial activity of Cannabis sativa in vivo have not been well established nor the consequences defined. This study was, therefore, designed to evaluate the effects of whole cannabis consumption on malaria-infected host. Methods: Thirty mice were inoculated with dose of 1×107 chloroquine-resistant Plasmodium berghei ANKA-infected erythrocyte and divided into six treatment groups. Cannabis diet formulations were prepared based on weighted percentages of dried cannabis and standard mice diet and the study animals were fed ad libitum. Chemosuppression of parasitemia, survival rates, parasite clearance, and recrudescence time were evaluated. Histopathological studies were performed on the prefrontal cortex (PFC) and hippocampus of the animals after 14 days' consumption of cannabis diet formulation by naive mice. Results: There was a significant difference (p<0.05) in the day-4 chemosuppression of parasitemia between the animals that were fed C. sativa and chloroquine relative to the untreated controls. There was also a significant difference in the survival rate (p<0.05) of animals fed C. sativa diet (40%, 20%, 10%, and 1%) in contrast to control animals on standard mice diet. A parasite clearance time of 2.18±0.4 was recorded in the chloroquine treatment group, whereas recrudescence in chloroquine group occurred on day 7. There were slight histomorphological changes in the PFC and cell densities of the dentate gyrus of the hippocampus of animals that were fed C. sativa.Conclusions:C. sativa displayed mild antimalarial activity in vivo. There was evident reduction in symptomatic manifestation of malaria disease, though unrelated to levels of parasitemia. This disease tolerance status may be beneficial, but may also constitute a transmission burden through asymptomatic carriage of parasites by habitual cannabis users.

Cannabis use is associated with unwanted health outcomes, including anxiety, depression, poor sleep hygiene, and disrupted cognitive functioning. However, research to date has not been able to disentangle the complexities of these relations, leaving behavioral health service providers lacking clear direction for treatment. A limiting factor may be the common practices for cannabis use assessment. Cannabis use is typically assessed by frequency, even though to estimate the amount of psychoactive compounds ingested potency, quantity, and route of administration should also be assessed. This study, one of the first of its kind, takes an important step in assessing cannabis use by studying the link between cannabis potency and behavioral health (i.e., physical and mental health) outcomes. Self-reported data were analyzed using the New Statistics, which focuses on effect sizes and confidence intervals, rather than null hypothesis significance testing. Findings were inconsistent, with some positive, some negative, and some trivial associations across four domains (i.e., demographic variables, cannabis use variables, mental health, and physical health). The most valuable discovery was the importance of method of administration in understanding the link between potency and health. We observed a "potency valley" (i.e., a range of potencies for which products were not available) between flower potencies and concentrate potencies. Further, collapsing potency data across flower and concentrated cannabis obscured important relations between cannabis potency and behavioral health outcomes. Findings suggest that to more fully understand the relation between cannabis potency and behavioral health outcomes, researchers should examine potency separately across routes of administration.

Over the past twenty years, the acceptance and use of medicinal cannabis has increased in the United States. However, there is still a lack of education and comfort as it relates to the therapeutic uses of botanical cannabis and cannabidiol in pharmacy professional curricula. Professional training programs have failed to keep pace with the evolving national landscape and growing acceptance of this therapy.In this manuscript, the current landscape of pharmacy professional involvement in the dispensing and administration of medicinal cannabis throughout the United States is described. A concern exists that there is a knowledge gap among pharmacists and pharmacy students, as demonstrated by recent survey results, related to the pharmacology, dosing, administration, adverse effects, drug interactions, and monitoring of both medicinal and recreational cannabis use.While cannabis use is still considered illegal by the federal government, it is imperative pharmacy educators prepare the next generation of pharmacists to be knowledgeable on the safe and effective use and communication tactics related to cannabis. As a therapy garnering national attention with growing support for use, education on this topic must be included in pharmacy curricula and pharmacy continuing education.

Background Earlier studies suggested a positive impact of spirituality on addictive disorders, but this effect has rarely been studied in a large adolescent and young adult population. Aim To examine the association between spiritual beliefs (general belief, the supporting role of spiritual belief, the critical role of spiritual belief) and potentially addictive behaviors (tobacco, alcohol, cannabis and other illegal drugs, excessive Internet use and gambling). Methods Data were collected using online self-report questionnaires among a sample of 5179 adolescents and young adults aged 15-24 years in post-mandatory education in Switzerland. Statistical analysis at bivariate and multivariate level was performed. Results At the bivariate level, spiritual beliefs were linked to a lower risk of tobacco smoking, alcohol misuse and cannabis use as well as an increased risk of Internet overuse and gambling. However, at the multivariate level, controlling for age, gender, language and place of birth, significant associations were found only for alcohol misuse, Internet overuse and gambling. Conclusion The study provides evidence that spiritual belief could protect youth from the risk of alcohol misuse but could also increase the risk of excessive Internet use and gambling. The role of spiritual beliefs in preventing or motivating these problematic behaviors is of great interest for adolescent health care providers and should be considered in the light of the separation-individuation process and transition from adolescence to adulthood.

Background/Objective: Although alcohol, tobacco and cannabis are the most widely consumed drugs, sparse data exist regarding polydrug use in adolescents and its relationship with impulsivity. This study aims to identify trajectories of polydrug use and analyze differences in impulsivity between them. Method: A total of 1,565 adolescents (54.4% males; mean age = 13.02, SD = 0.57) were annually assessed over three years using the Barratt Impulsiveness Scale, the Zuckerman Impulsive Sensation Seeking Scale, a Stroop Test and a Delay Discounting Task. Frequency of alcohol, tobacco, and cannabis use, intoxication episodes and problem drinking were also assessed. Polydrug trajectories were identified using latent class mixed modelling. To examine differences in self-reported and behavioral impulsivity two mixed multivariate analyses of covariance were used. Results: Three trajectories of substance use were found. The 'Experimental use' and the 'Early use' trajectories presented the lowest and highest impulsivity, respectively. Substance use increases in the 'Telescoped used' trajectory were associated with parallel increases in impulsivity. Conclusions: individuals with divergent patterns of substance use during adolescence differ in their impulsiveness, primarily in general impulsivity and sensation seeking. Present findings suggest the relevance of these facets as possible targets for interventions preventing the onset and escalation of substance use.

We investigated whether adult attention-deficit/hyperactivity disorder (ADHD) predicts risky substance use and substance use disorders (SUDs), and its impact on the course of these problematic substance use patterns. Our sample included 4975 Swiss men (mean age 20 ± 1.2 years) who participated in the baseline and 15-month follow-up assessments of the Cohort Study on Substance Use Risk Factors. We examined: (1) the contribution of ADHD, as assessed at baseline, on the risky use of alcohol, nicotine and cannabis, and their corresponding use disorders (AUD, NUD, CUD) at follow-up; and (2) the association between ADHD and the course of outcomes (i.e., absence, initiation, maturing out, persistence) over 15 months. All analyses were adjusted for socio-demographics and co-morbidity. Men with ADHD were more likely to exhibit persistent risky alcohol and nicotine use, and to mature out of risky cannabis use. ADHD at baseline was positively linked to AUD and negatively to CUD at follow-up, but not to NUD. For all SUDs, ADHD had a positive association with use persistence and maturing out. Comparing these two trajectories revealed that early age of alcohol use initiation distinguished between persistence and maturing out of AUD, while the course of NUD and CUD was related to ADHD symptoms and SUD severity at baseline. Already in their early twenties, men with ADHD are especially likely to exhibit persistent problematic substance use patterns. Substance-specific prevention strategies, particularly implemented before early adulthood, may be crucial to reducing the development and persistence of pathological patterns in such individuals.

Liability to alcohol dependence (AD) is heritable, but little is known about its complex polygenic architecture or its genetic relationship with other disorders. To discover loci associated with AD and characterize the relationship between AD and other psychiatric and behavioral outcomes, we carried out the largest genome-wide association study to date of DSM-IV-diagnosed AD. Genome-wide data on 14,904 individuals with AD and 37,944 controls from 28 case-control and family-based studies were meta-analyzed, stratified by genetic ancestry (European, n = 46,568; African, n = 6,280). Independent, genome-wide significant effects of different ADH1B variants were identified in European (rs1229984; P = 9.8 × 10-13) and African ancestries (rs2066702; P = 2.2 × 10-9). Significant genetic correlations were observed with 17 phenotypes, including schizophrenia, attention deficit-hyperactivity disorder, depression, and use of cigarettes and cannabis. The genetic underpinnings of AD only partially overlap with those for alcohol consumption, underscoring the genetic distinction between pathological and nonpathological drinking behaviors.

Fatty acid conjugates of hydroxy-metabolites of tetrahydrocannabinol (THC) or cannabinol have already been reported as metabolites in rats. In the herein presented investigation, palmitic acid esters of THC and its primary metabolite 11-hydroxy-delta9-tetrahydrocannabinol (11-OH-THC) were synthesized using esterification with palmitic acid chloride. Structural elucidation of the products was conducted using nuclear magnetic resonance spectroscopy (NMR) and liquid chromatography coupled to quadrupole time of flight mass spectrometry (LC-QToF-MS). For the confirmation of a previous cannabis use, body fluids (femoral blood, heart blood, urine, bile) of 27 death cases (all with known cannabis use), including adipose tissue homogenates of six of these cases as well as eleven plasma samples (probably all with regular cannabis use, confirmed by a high 11-nor-9-carboxy-delta9-tetrahydrocannabinol (THC-COOH) concentration (except one sample, >200ng/mL), were tested for THC and its main metabolites 11-OH-THC and THC-COOH using gas chromatography coupled to mass spectrometry (GC-MS). These samples as well as further tissue homogenates of autopsy cases (liver, kidney, brain) were additionally tested for the presence of THC palmitic acid ester or 11-OH-THC palmitic acid diester by means of a liquid chromatographic triple quadrupole mass spectrometric (LC-QQQ-MS) method, in order to evaluate a possible presence of these conjugates in humans. In none of the analyzed samples (in total 196 specimens; plasma (N=11), femoral blood (N=23), heart blood (N=25), urine (N=23), bile (N=27), liver (N=27), kidney (N=27), brain (N=27), adipose tissue (N=6)), palmitic acid esters of THC or 11-OH-THC could be proven. Even if the existence of these esters in human samples cannot be ruled out definitely, suitability as cannabis consumption markers does not seem likely based on our findings.

Presented herein are RNA expression data linked to the exposure of human lung epithelial cells to either low dose radon-emitting rock, tobacco smoke or cannabis smoke. Two cell lines were used, one representing a 'normal' lung epithelial cell (BEAS-2B, derived from immortilized bronchial epithelial cells from a cadaver) and one representing a 'cancerous' lung epithelial cell (NCI-H1975, derived from a primary lung adenocarcinoma from a non-smoker). Control cells were cultured under standard conditions. Test cells were either (a) continuously cultured in the presence of pulverized uranium-containing rock emitting 38 Bq/m3 radon, or (b) exposed five days a week, to a 1:10,000 dilution of either tobacco or cannabis smoke from one cigarette. RNA was extracted from the cells at various time-points over a period of 1-17 weeks (7-140 days). cDNA libraries were prepared from the RNA, and the libraries were sequenced. Raw, aligned sequencing data, from 38 biosamples, are available through a public repository. Differential gene expression data, relating to control and test samples from various time-points, are linked to this article. Detailed analyses relating to these data can be found in the article "Human lung epithelial cells cultured in the presence of radon-emitting rock experience gene expression changes similar to those associated with tobacco smoke exposure" [1].

The purpose of this chapter is to highlight the rich tradition of self-experiments (SEs) with psychoactive substances carried out by scientists and therapists for more than a century. Scientifically inspired controlled SEs dominated until the end of the twentieth century, when ethical requirements minimized controlled SEs and "wild" SEs expanded particularly with the emergence of new psychoactive substances. The review focuses on laughing gas (nitrous oxide), cannabis, cocaine, hallucinogens, entactogens, and dissociative hallucinogens. This is due to the fact that substances that induce "complex" effects such as alteration of space/time experience, ego dissolution, and increased feelings and insights (e.g., hallucinogens, entactogens) represent by far the majority of SEs, whereas SEs with substances inducing "simple" effects such as euphoria, anxiolysis, dissociation, or emotional blunting (e.g., cocaine, opioids) are much rarer or even absent (e.g., benzodiazepines). Complex drug effects are much harder to describe, thus allowing SEs to fulfill a more important function.SEs with psychoactive drugs appeared to emerge in the mid-eighteenth century, which triggered a long-standing tradition throughout the nineteenth and early twentieth century. SEs have been de facto performed for a variety of reasons, ranging from establishing scientific knowledge and gaining philosophical insights to compensating for personal deficits. Self-experimenters can be divided into two general types. Besides their scientific intentions, "exploratory" self-experimenters intend to expand awareness and insight, whereas "compensatory" self-experimenters might aim for coping with psychiatric symptoms or personality deficits. Scientific limitations of SEs are obvious when compared to double-blind, randomized, placebo-controlled trials. Whereas the former might lead to more "realistic" detailed description of subjective effects, the latter lead to more solid results in respect to objectively measurable "average" effects. Possible adverse effects of SEs were identified that resulted in loss of scientific objectivity and decreased control over substance use and addiction, development of isolation, problematic group dynamics, and "social autism."

To evaluate the effectiveness of the online Climate Schools: Ecstasy and Emerging Drugs module over 2 years, and examine the impact of intervention dose on outcomes.Cluster randomised controlled trial.Secondary schools in Australia.1126 students (aged 14.9 years) from 11 schools.Five schools were randomly allocated to the four-lesson internet-based Climate Schools: Ecstasy and Emerging Drugs module. This universal intervention uses cartoon storylines to deliver harm-minimisation information about ecstasy and new psychoactive substances (NPS). It was delivered during health education classes over 4 weeks. Six schools were randomised to the control group (health education as usual). Participants were not blinded to intervention allocation.Students completed self-report surveys at baseline, post-test, 6, 12 and 24 months post-baseline. Intentions to use ecstasy and NPS (including synthetic cannabis and synthetic stimulants), knowledge about ecstasy and NPS and lifetime use of ecstasy and NPS were assessed. This paper reports the results at 24 months post-baseline.Mixed effects regressions were conducted to analyse intervention effects from baseline to 24 months. Post hoc analyses using Inverse Probability of Treatment Weighting compared controls with students who: i) completed all four lessons ('full dose') and ii) partially completed the intervention (≤three lessons, 'incomplete dose').Primary analyses found that controls were significantly more likely to intend on using synthetic cannabis compared with intervention group students (OR=3.56, p=0.01). Results from the weighted analyses indicated that controls reported significantly lower knowledge about ecstasy (p=0.001) and NPS (p=0.04) compared with the full-dose group. No significant differences were observed between the incomplete dose and control groups.The online intervention was effective in modifying students' intentions to use synthetic cannabis up to 24 months; however, this study highlights the importance of delivering prevention programmes in full to maximise student outcomes.ACTRN12613000708752.

Prior research that assesses the relationship between cannabis policy and prevalence rates has yielded mixed results, perhaps due to the varying rigor of these investigations. Addressing some of these issues in rigor and informed by a rational choice theory (RCT), we hypothesize that those policies on the more punitive end of McDonald and colleagues' classification will be most effective. Examining legislation in 27 countries utilizing the Second International Self-Report Delinquency Study (ISRD-2) through hierarchical linear modeling (HLM) models with both individual- and country-level controls, we find little support for these hypotheses. Instead, results from our analysis largely indicate that the variation in country prevalence rates from 2005 to 2007 was not significantly related to cannabis control policy. We comment on possible policy implications for these preliminary results.

Liberalization of marijuana laws in Colorado contributed to increases in cannabis-related adverse events over time. We examined characteristics of patients with healthcare encounters possibly related to cannabis and assessed the temporal association between legalization of recreational marijuana and healthcare encounters possibly attributed to cannabis.Annual encounter rates possibly related to cannabis and alcohol were compared using negative binomial regression. Two-time intervals, pre/post-recreational marijuana legalization (January 2009 to December 2013 and January 2014 to December 2015, respectively) were used to examine changes in monthly rates of emergency encounters and hospitalizations possibly related to cannabis. Level and trend changes on encounter rates by legalization period were assessed using interrupted time series analyses. Encounters possibly related to alcohol were used as a comparator group.Most encounters identified during the study period had alcohol-related International Classification of Diseases Diagnosis and Procedural Codes (ICD-9/10-CM) codes (94.8% vs 5.2% for cannabis). Patients with encounters possibly related to cannabis were younger, more likely to be hospitalized and more likely to be admitted to the psychiatric unit than patients with encounters possibly related to alcohol. Initial and sustained effects of encounter rates possibly related to cannabis demonstrated an increased trend in slope before and after recreational marijuana legalization. The slope became more abrupt following legalization with a significant increase in trend during the post-legalization period (β = 2.7, standard error = 0.3, ρ < 0.0001). No significant change was noted for encounters possibly related to alcohol.Additional research should identify patients at highest risk of an adverse health event related to cannabis and quantify costs associated with cannabis-related healthcare delivery.

Epidemiological and roadside studies suggest that driving after cannabis use (DACU) is prevalent in the United States, and rates have increased following legalization or decriminalization of cannabis in some U.S. states. Reinforcing value of addictive substances (as measured by behavioral economic demand tasks), is an emerging risk factor for driving under the influence. This study sought to expand upon the previously documented link between alcohol demand and driving after drinking by examining whether similar associations exist between cannabis demand and DACU. A large diverse sample of adults (N = 733) recruited via an online crowd-sourcing platform (Amazon Mechanical Turk) competed a validated marijuana purchase task assessing cannabis consumption across a range of prices and validated assessments of DACU, cannabis misuse, and demographics. In analyses of covariance controlling for age, sex, income, and level of cannabis misuse, individuals who endorsed DACU showed elevated cannabis demand across all demand indices examined (ps < .05). Logistic regression indicated that increased intensity of demand was uniquely associated with a greater likelihood of DACU (odds ratio [OR] = 1.61-2.02, ps < .03). Breakpoint, maximum expenditure, and price point corresponding to maximum expenditure uniquely predicted DACU in separate models (OR = 1.41-1.68, ps < .03) but not in a combined model (ORs < 1.36, ps > .47). These results provide initial evidence that elevated cannabis demand may be a distal risk factor for DACU, but future research is needed to clarify the specific relationship between cannabis demand and DACU. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

This large-scale population-based prospective study examined the association between depressive symptoms and cognitive performance at baseline with later functioning in middle-aged adults.The Center for Epidemiologic Studies Depression Scale, the Digit Symbol Substitution Test (DSST), the Trail Making Test B (TMT-B), and the Semantic Verbal Fluency test (SVF) were completed at baseline by 7,426 participants aged ≥ 45 years from February 2012 to December 2013. Role limitations and social functioning were later assessed with the second version of the 12-Item Short Form Health Survey. The association between depressive symptoms and cognitive performance at baseline with functioning at follow-up was examined using general linear models and mediation analyses including sex, age, education, alcohol intake, and cannabis use as covariates.Altered functioning at follow-up was predicted by depressive symptoms (β per standard deviation [95% confidence intervals]: -1.10 [-1.16 to -1.03] and -1.02 [-1.08, -0.96] for role limitations and social functioning, respectively) and DSST, TMT-B, and SVF performance (for role limitations: 0.11 [0.09 to 0.14], -0.11 [-0.13 to -0.08], and 0.03 [0.01 to 0.06], respectively; for social functioning: 0.10 [0.07 to 0.12], -0.08 [-0.11 to -0.06], and 0.04 [0.01 to 0.05], respectively) at baseline. Depressive symptoms were associated with poorer cognitive performance at baseline (-0.19 [-0.25 to -0.13], 0.15 [0.08 to 0.21], and -0.11 [-0.17 to -0.04], respectively). Cognitive performance accounted for only 0.3%-1.4% of the relationship between depressive symptoms and functioning. In contrast, depressive symptoms accounted for 19.5%-43.7% of the association between cognitive performance and functioning.In middle-aged adults from the general population, cognitive impairment is unlikely to substantially explain the association between depressive symptoms and later role limitations and social functioning.

This study estimated whether and how the 12-month prevalence of cannabis use disorder among US youth aged 12-17 and emerging adults aged 18-25 varied by time since first cannabis use.Repeated cross-sectional survey data from the 2015-17 National Surveys on Drug Use and Health (NSDUH).United States.A total of 101 000 NSDUH participants aged 12-25.Past 12-month cannabis use disorder was assessed using DSM-IV criteria.Among youth, the life-time prevalence of cannabis use was 15.3% [95% confidence interval (CI) = 14.86-15.65%]. Among emerging adults, the life-time prevalence of cannabis use was 52.4% (95% CI = 51.77-53.01%). The adjusted 12-month prevalence of cannabis use disorder among youth with life-time cannabis use was 10.9% (95% CI = 9.24-12.75%) in the first year after starting cannabis use, 15.3% (95% CI = 13.68-17.12%) in the second year, 17.7% (95% CI = 15.55-19.97%) in the third year and 20.6% (95% CI = 18.23-23.17%) in the fourth year and beyond, which was consistently higher after the first year (linear trend only: P < 0.0001). The adjusted 12-month prevalence of cannabis use disorder among emerging adults with life-time use ranged from 5.6% (95% CI = 4.26-7.23%) in the first year after starting cannabis use, 7.7% (95% CI = 6.45-9.17%) in the second year and 9.1% (95% CI = 7.81-10.57%) in the third year to 10.5% (95% CI = 9.87%-11.12%) in the fourth year and beyond, which was consistently higher after the first year (linear trend only: P < 0.0001). Within each time-frame since first cannabis use, the adjusted 12-month prevalence of cannabis use disorder was higher among youth life-time users than their emerging adult counterparts.Among youth and emerging adults in the United States, the prevalence of cannabis use disorder appears to increase with time since initiation of use and is higher among youth than among emerging adults during each examined time-frame.

The high rate of cannabis (CAN) use in emerging adults is concerning given prior research suggesting neurocognitive deficits associated with CAN use in youth. Regular CAN use downregulates endocannabinoid activity, while aerobic exercise upregulates cannabinoid receptor 1 activity and releases endocannabinoids. Here we investigate the influence of regular CAN use on neuropsychological performance, and whether aerobic fitness moderates these effects.Seventy-nine young adults (37 CAN users) aged 16-26 participated. Groups were balanced for aerobic fitness level. Exclusion criteria included: left-handedness, past-year independent Axis-I disorders, major medical/neurologic disorders, prenatal issues, or prenatal alcohol/illicit drug exposure. After 3 weeks of abstinence, participants completed a neuropsychological battery and a maximal oxygen consumption test (VO2 max). Multiple regressions tested whether past-year CAN use, VO2 max, and CAN*VO2 max interaction predicted neuropsychological performance, controlling for past-year alcohol use, cotinine, gender, and depression symptoms.Increased CAN use was associated with decreased performance on working memory and psychomotor tasks. High aerobic fitness level was related to better performance on visual memory, verbal fluency, and sequencing ability. CAN*VO2 max predicted performance of psychomotor speed, visual memory, and sequencing ability.Following monitored abstinence, increased CAN use was associated with poorer performance in working memory and psychomotor speed. Higher aerobic fitness level moderated the impact of CAN on visual memory, executive function and psychomotor speed, as more aerobically fit CAN users demonstrated better performance relative to low-fit users. Therefore, aerobic fitness may present an affordable and efficacious method to improve cognitive functioning in CAN users. (JINS, 2019, 25, 134-145).

The prevalence of opioid-associated morbidity and mortality underscores the need for research on non-opioid treatments for chronic non-cancer pain (CNCP). Pain is the most common medical condition for which patients request medical cannabis. Limited research indicates that patients are interested in cannabis as a potential addition to or replacement for opioid medication. This analysis reports on CNCP patient and clinician perceptions about the co-use of cannabis and opioids for CNCP management.We interviewed 23 clinicians and 46 CNCP patients, using semi-structured interview guides, from six safety-net clinics across the San Francisco Bay Area, and 5 key stakeholders involved in CNCP management. We used a modified grounded theory approach to code and analyze transcripts.CNCP patients described potential benefits of co-use of cannabis and opioids for pain management and concerns about dosing and addictive potential. Patients reported seeking cannabis when unable to obtain prescription opioids. Clinicians stated that their patients reported cannabis being helpful in managing pain symptoms. Clinicians expressed concerns about the potential exacerbation of mental health issues resulting from cannabis use.Clinicians are hampered by a lack of clinically relevant information about cannabis use, efficacy and side-effects. Currently no guidelines exist for clinicians to address opioid and cannabis co-use, or to discuss the risk and benefits of cannabis for CNCP management, including side effects. Cannabis and opioid co-use was commonly reported by patients in our sample, yet rarely addressed during clinical CNCP care. Further research is needed on the risks and benefits of cannabis and opioid co-use.

Patients with schizophrenia and substance related comorbidity or substance induced psychotic disorder are difficult to treat. Although the prevalence of a comorbid substance use is approximately 40% in schizophrenia, such patients are usually excluded from clinical trials. We therefore performed a random-effects meta-analysis of all randomized controlled antipsychotic drug trials in this patient subgroup. We searched multiple databases up to May, 2018. The primary outcome was the reduction of substance user; secondary outcomes were craving, mean reduction of substance use, overall change in schizophrenia symptoms, positive and negative symptoms, response, dropouts, quality of life, social functioning, weight gain, sedation, prolactin, extrapyramidal side effects and use of antiparkinsonian medication. We identified 27 references from 19 RCTs published from 1999 to March 2017 including 1742 participants. The most frequent types of substance abuse were cannabis (8 studies) and cocaine (6 studies) use/dependence. Clozapine was superior to other antipsychotics for reduction of substance use and risperidone to olanzapine for craving. Olanzapine, clozapine and risperidone showed superiority for symptom reduction compared to some other drugs. When reported, results of side-effects followed known patterns. The evidence-base is considerable (19 RCTs), however, firm conclusions cannot be drawn due to small sample sizes of individual studies and insufficient reporting.

The therapeutic potential of cannabinoids has been truly constrained heretofore due to their strong psychoactive effects and their high lipophilicity. In this context, precisely due to the lack of psychoactive properties, cannabidiol (CBD), the second major component of Cannabis sativa, arises as the phytocannabinoid with the most auspicious therapeutic potential. Hence, the incorporation of CBD in lipid nanocapsules (LNCs) will contribute to overcome the dosing problems associated with cannabinoids. Herein, we have prepared LNCs decorated and loaded with CBD for glioma therapy and screened in vitro their critical parameters. On the one hand, we have encapsulated CBD into the oily core of LNCs to test their in vitro efficacy as extended-release carriers against the human glioblastoma cell line U373MG. The in vitro antitumor effect was highly dependent on the size of LNCs due to its pivotal role in the extent of CBD release. Effectively, a comparison between two differently-sized LNCs (namely, 20-nm and 50-nm sized carriers) showed that the smaller LNCs reduced by 3.0-fold the IC50 value of their 50-nm sized counterparts. On the other hand, to explore the potential of this phytocannabinoid to target any of the cannabinoid receptors overexpressed in glioma cells, we decorated the LNCs with CBD. This functionalization strategy enhanced the in vitro glioma targeting by 3.4-fold in comparison with their equally-sized undecorated counterparts. Lastly, the combination of CBD-loading with CBD-functionalization further reduced the IC50 values. Hence, the potential of these two strategies of CBD incorporation into LNCs deserves subsequent in vivo evaluation.

Substance induced psychotic disorders (SIPD) have been historically considered as associated with better clinical and functional outcomes than other psychotic diagnoses. As a result, treatments for those with SIPD are often considerably less intensive, yet this is not based on evidence. The present study aimed to examine whether differences exist between those with SIPD and other first episode psychosis (FEP) diagnoses in regards to demographic and clinical factors, and to determine the symptomatic, clinical and functional outcomes in those with SIPD.This study included all young people aged 15-24 who presented with a FEP to the Early Psychosis Prevention and Intervention Centre between 01/01/2011 and 31/12/2013. Group differences were analysed with independent samples t-tests and chi-square analyses and equivalent non-parametric tests as appropriate. Where applicable, odds ratios were calculated.544 young people presented with a FEP and 10.3% (N = 56) were diagnosed with SIPD. Individuals with SIPD were more likely to be male, unemployed, and have a comorbid substance use disorder. There were no significant differences between groups regarding duration of untreated psychosis, severity of psychotic symptoms, time to remission, or rates of relapse. Those with SIPD were less likely to be employed or engaged in study at discharge and 35.7% of those with SIPD had a change of diagnosis to a schizophrenia spectrum or bipolar disorder after a median of 84 weeks.Young people diagnosed with SIPD should be an important focus of early intervention services and receive comparable treatment to those with other psychotic diagnoses.

As medicinal and recreational marijuana use broadens across the United States, knowledge of its effects on the body will become increasingly important to all health care providers, including surgeons.We performed a literature review of Pubmed for articles discussing the basic science related to cannabinoids, as well as articles regarding cannabinoid medications, and cannabis use in surgical patients.The primary components in the cannabis plant, tetrahydrocannabinol (THC) and cannabidiol (CBD), have been made available in numerous forms and formulations to treat multiple medical conditions, and recreational access to marijuana is increasing. Of particular importance to the surgeon may be their effects on prolonging intestinal motility, decreasing inflammation, increasing hunger, mitigating pain, and reducing nausea and vomiting. Perioperative use of medicinal or recreational marijuana will become increasingly prevalent, and the surgeon should be aware of the positive and negative effects of these cannabinoids.

The following chapter offers an overview of results of experimental studies conducted among healthy individuals examining the effects of acute administration of Δ9-THC and other cannabinoids, alone or in combination, on brain function and behavior, also as a function of previous cannabis exposure. In light of their methodological design, these studies have advanced the understanding of the neurobiological mechanisms increasing the risk of long-lasting cognitive dysfunction as well as psychosis in regular cannabis users. Also, direct and indirect evidence supports an alteration of different neurotransmitters, such as dopamine, glutamate, and gamma-aminobutyric acid, in modulating the manifestation of neurocognitive dysfunction and psychosis in the context of both acute and chronic cannabis exposure. Future multimodal neuroimaging studies will integrate the longitudinal information to track the long-term changes in brain neurochemistry and neurophysiology as well as other potential biomarkers induced by sustained cannabis use.

Culpability studies, a common study design in the cannabis crash risk literature, typically report odds-ratios (OR) indicating the raised risks of a culpable accident. This parameter is of unclear policy relevance, and is frequently misinterpreted as an estimate of the increased crash risk, a practice that introduces a substantial "interpretational bias".A Bayesian statistical model for culpability study counts is developed to provide inference for both culpable and total crash risks, with a hierarchical effect specification to allow for meta-analysis across studies with potentially heterogeneous risk parameter values. The model is assessed in a bootstrap study and applied to data from 13 published culpability studies.The model outperforms the culpability OR in bootstrap analyses. Used on actual study data, the average increase in crash risk is estimated at 1.28 (1.16-1.40). The pooled increased risk of a culpable crash is estimated as 1.42 (95% credibility interval 1.11-1.75), which is similar to pooled estimates using traditional ORs (1.46, 95% CI: 1.24-1.72). The attributable risk fraction of cannabis impaired driving is estimated to lie below 2% for all but two of the included studies.Culpability ORs exaggerate risk increases and parameter uncertainty when misinterpreted as total crash ORs. The increased crash risk associated with THC-positive drivers in culpability studies is low.

Evidence obtained in recent decades has demonstrated that the brain still matures in adolescence. Changes in neural connectivity occur in different regions, including cortical and subcortical structures, which undergo modifications in white and gray matter densities. These alterations concomitantly occur in some neurotransmitter systems and hormone secretion, which markedly influence the refinement of certain brain areas and neural circuits. The immaturity of the adolescent brain makes it more vulnerable to the effects of alcohol and drug abuse, whose use can trigger long-term behavioral dysfunction. This article reviews the action of alcohol and drug abuse (cannabis, cocaine, opioids, amphetamines, anabolic androgenic steroids) in the adolescent brain, and their impact on both cognition and behavioral dysfunction, including predisposition to drug abuse in later life. It also discusses recent evidence that indicates the role of the neuroimmune system response and neuroinflammation as mechanisms that participate in many actions of ethanol and drug abuse in adolescence, including the neurotoxicity and alterations in neurocircuitry that contribute to the dysfunctional behaviors associated with addiction. The new data suggest the therapeutic potential of anti-inflammatory targets to prevent the long-term consequences of drug abuse in adolescence.

Mental, personality and substance use disorders are over represented among prisoners and aggressive individuals. The psychopathological and biological markers linked to mental functioning remain still unclear. In particular, the role of trace elements in mental illness is still matter of debate. Here, we investigated whether trace elements are correlated to specific psychopathological phenotype groups.Axis I and II disorders, aggression, impulsivity, adult attention deficit/hyperactivity disorders (ADHD) indices and serum levels of zinc, copper and cadmium were evaluated in 160 male prisoners.Using latent class analysis we could subdivide prisoners into three distinct psychopathological classes: Class 1 characterized by low prevalence of aggression, personality disorders and substance abuse/dependence (alcohol, cannabis, cocaine); Class 2 represented by low prevalence of aggression and high prevalence of personality disorders and substance abuse/dependence; Class 3 defined by high prevalence of aggression, personality disorders and substance abuse/dependence. Serum levels of zinc were higher in Class 2 and 3 compared to Class 1. Moreover, Class 3 was associated with higher scores of impulsivity and ADHD indices.Our results suggest that impulsivity but also adult ADHD indices are related to aggressive behaviour, and higher zinc levels are linked to personality disorders and addictions, but not to aggression.

International public policy on age of first alcoholic drink (AFD) has emphasised the long-term benefits of delaying AFD. This study aimed to compare AFD to age of first intoxication (AFI) as predictors of substance use disorder and mental disorder outcomes in adulthood.Data were obtained from a longitudinal birth cohort in Christchurch, New Zealand. Participants were born in 1977. Analysis samples ranged from n = 1025 (age 18) to n = 962 (age 35). Measures of AFD and AFI were generated using parental- and self-report data collected from age 11. Outcomes at age 18-35 were alcohol quantity consumed, DSM-IV alcohol use disorder (AUD) and AUD symptoms, major depression, anxiety disorder, and nicotine, cannabis, and other illicit drug dependence. Covariate factors measured during childhood included family socioeconomic status, family functioning, parental alcohol-related attitudes/behaviours, and individual factors.There was a significant unadjusted association between AFD and symptoms of AUD (p < .001) and nicotine dependence (p < .05) but not other outcomes. AFI was significantly (p < .05) associated with all outcomes. After adjustment for covariates, the association between AFD and outcomes was not statistically significant. Conversely, in adjusted models, statistically significant (p < .05) associations remained between AFI and all AUD and substance use disorder outcomes but not alcohol consumption or mental disorder outcomes.AFI was a more robust predictor of adult substance use disorder outcomes than AFD. Public health and policy interventions aimed at prevention of long term harms from alcohol should therefore focus on AFI rather than AFD.

The use of marijuana concentrates has escalated in recent years with butane extracts appearing particularly popular. The administration of butane hash oil, colloquially referred to as "dabbing," is distinct from traditional flower cannabis usage due to the THC content of samples and the presence of impurities such as unpurged butane. While this may confer heightened risk to the user, additional significant concerns are tied to fires and explosions. Using butane as a solvent in amateur "blasting" methods may result in a flammable vapor pooling in enclosed spaces and igniting when exposed to a spark. As research on butane extract users, amateur production techniques, health risks, and legality is in its infancy, we explored existing studies on the topic to create a review of substantiated knowledge related to THC extracted using butane. The resulting assessment centers on three areas: 1) dab users including both recreational users and medical marijuana patients; 2) butane extraction techniques including illicit amateur open methods and the safer closed-loop system employed in medicinal/recreational states; and 3) risks, both related to fires and legality. We follow the presentation of this material with a summary of the (mis)information reaching the public in print and online sources so that public educational campaigns can focus on dispelling the inaccuracies and false notions of safety that may be tied to amateur production.

The consumption of alcohol and other drugs causes social and health problems in industrialized societies. Furthermore, alcohol and drug consumption in the workplace is associated with work accidents, absenteeism and low productivity. The aim of the current study is to reduce alcohol and drug consumption among workers in the service industry and, as a secondary aim, to improve their healthy habits through the reduction of alcohol and other drug consumption in their leisure time.This nonrandomized, single-group study was conducted in 12 work centers. The intervention began in 2009 and emphasized 1) health promotion and health monitoring, which included a) alcohol and drug awareness and b) the evaluation and monitoring of alcohol and drug consumption through a semistructured interview designed to assess risky consumption; urine tests aimed at detecting alcohol, cannabis and cocaine use; an Alcotest based on expired air to test for the recent consumption of alcohol and a saliva exam to test for the recent consumption of six drugs; and 2) secondary prevention if risky consumption was identified. Risky alcohol consumption was defined as the ingestion of more than 28 standard drink units (SDUs)/week among men and more than 17 SDUs/week among women (taking into account both work and leisure time). Drug consumption was considered risky consumption.A total of 1103 workers participated, and each received 5 h of awareness training. Those who presented with risky consumption received secondary prevention training. The prevalence of risky alcohol consumption decreased by 4.1% (baseline: 14.7% reduced to 10.6% in the first year; p = 0.001), a reduction that was maintained over a 3-year follow-up period.A comprehensive program of worker health surveillance that involves stakeholders and includes monitoring can be a means of potentially improving compliance with workplace promotion programs, resulting in the facilitation of such beneficial, desired behavior change in areas such as alcohol and drug consumption.

Over the past decade, availability and use of novel psychoactive substances such as synthetic cannabinoid receptor agonists (SCRA) have proliferated globally. However, the prevalence of SCRAs use remains uncertain, as does the degree to which individuals reporting SCRA use prefer SCRA to other drugs.In April 2017, a total of 500 anonymous surveys were completed by clients enrolled in a residential drug recovery program. Chi-square and t tests were used to examine significant differences between those who had ever used SCRA and those who had not. Logistic regression analysis was conducted in order to determine which other substances used within the past 12 months were significantly associated with past-12-month SCRA use.About 69% (68.4%) of clients reported lifetime SCRA use. Those reporting SCRA use were predominantly younger ([Formula: see text] = 32.5 vs. 40.7, P < .001), single (60.3% vs. 48.1%, P = .011), and white (87.1% vs. 77.7%, P = .008) and were more likely to have experienced past-12-month homelessness (6.5% vs. 3.2%, P = .004). This group had higher rates of probation/parole involvement (79.2% vs. 61.8%, P < .001) and incarceration (91.8% vs. 79.6%, P < .001). Individuals reporting SCRA use also showed extensive substance use histories and favored heroin, opioids, and amphetamines compared with SCRA. Only 5.2% of the SCRA-using group stated that SCRA was a preferred substance, and only 11.8% reported that they would try SCRA again. E-cigarettes (adjusted odds ratio [AOR] = 1.88), traditional cannabis (AOR = 3.87), amphetamines (AOR = 2.20), and synthetic cathinones (AOR = 3.51) were significantly associated with past-12-month SCRA use. Motivations for use included circumnavigating drug screens and peer influence. Approximately half of those who tried SCRA reported adverse effects associated with use.Prevalence of SCRA use among individuals with a history of substance misuse and criminal justice system involvement is high; however, SCRA are not indicated as a preferred drug.

To determine whether cannabis use during adolescence can increase risk not only for cannabis use disorder (CUD) but also for conduct problems, potentially mediated by exposure to peers who use cannabis.Longitudinal study analyzing four waves of longitudinal data from 364 racially and socio-economically diverse, urban, US community youth (at baseline: Mage  = 13.51 (0.95); 49.1% female).Self-reports of cannabis use, conduct problems, proportion of peers using cannabis and CUD criteria at the final wave were analyzed using a method sensitive to changes over development, the random-intercept cross-lagged panel model.Change in cannabis use did not predict changes in conduct problems or peer cannabis use over time, controlling for gender, race-ethnicity and socio-economic status. Instead, increases in conduct problems predicted increases in cannabis use and ultimately CUD, with some of the effect mediated by increases in the prevalence of peer cannabis use [β = 0.12, 95% confidence interval (CI) = 0.07, 0.20]. Additionally, affiliation with peers who used cannabis predicted subsequent CUD via increased personal cannabis use (β = 0.08, 95% CI = 0.04, 0.14). Significant within-person betas for the cross-lagged effects ranged between 0.20 and 0.27.Cannabis use in adolescence does not appear to lead to greater conduct problems or association with cannabis-using peers apart from pre-existing conduct problems. Instead, adolescents who (1) increasingly affiliate with cannabis-using peers or (2) have increasing levels of conduct problems are more likely to use cannabis, and this cascading chain of events appears to predict cannabis use disorder in emerging adulthood.

Twenty-nine states have bypassed federal regulations by legalizing marijuana (MJ) either medicinally, recreationally or both. The FDA states that there is no empirical evidence that MJ is effective to treat these disorders. With over a billion individuals living with a disability across the globe, it is crucial to fully research the efficaciousness and safety of medical MJ to treat this population. The purpose to present the results of a scoping review of studies focused on the levels of evidence currently available on medical MJ's efficacy in treatment across a large range of disabilities.Databases were searched for research articles on the current level of evidence to support medical MJ use among people with disabilities.Forty-one peer reviewed articles met the inclusion criteria. Articles focused on attention deficit hyperactivity disorder, post-traumatic stress disorder, depression, schizophrenia, spinal cord injury, multiple sclerosis/movement disorders, fibromyalgia, epilepsy, with some that focused on multiple disabilities.The level of evidence for the use of medical MJ among people with disabilities varies greatly, and has a clear lack of methodologically sound studies. Overall, medical MJ does not improve the level of functioning, but it may improve the overall quality of life for people with disabilities. Implications for Rehabilitation Epilepsy can be a disabling chronic disorder which not only impacts physically but can restricts quality of life. Quality of life is diminished even more with treatment resistant epilepsy. Chronic pain is the leading cause of disability and is the most common cause of long-term disability. There is sufficient evidence that medical marijuana is effective in treating epileptic seizures and chronic pain. Medical marijuana may improve the level of functioning and quality of life for individuals with certain disabilities.

Insomnia is a common problem, however, its prevalence has never been examined in Indian population. Moreover, a number of psychiatric disorders have been found to be associated with insomnia in clinical population, but this association has scarcely been examined in general population.This epidemiological study was done in an urban and a rural population. Subjects were selected using Kish method. After obtaining informed consent, psychiatric disorders were diagnosed using Hindi version of Mini International Neuropsychiatric Interview. Hindi version of Insomnia Severity Index was used to diagnose insomnia.1700 subjects were included in this study. In this study, prevalence of insomnia was 10.3%. Its prevalence increased with increasing years of education (p=0.009). Insomnia was more frequent in subjects living in joint families (p<0.001), having higher education (p=0.009), those who were separated (p<0.001), among subjects belonging to middle socio-economic status (p<0.001) and in urban population compared to semi-urban and rural population (p<0.001). Insomnia was also more frequent among subjects with major depressive disorder, generalized anxiety disorder, alcohol dependence, cannabis dependence and tobacco use. However, binary logistic regression analysis showed that only higher education, unemployment, generalized anxiety disorder and tobacco use were associated with insomnia.Insomnia in general population is associated with higher education, unemployment, generalized anxiety disorders and tobacco use.

The plant Cannabis sativa produces over 140 known cannabinoids. These chemicals generate considerable interest in the medical research community for their possible application to several intractable disease conditions. Recent reports have prompted parents to strongly consider Cannabis products to treat their children with drug resistant epilepsy. Physicians, though, are reluctant to prescribe Cannabis products due to confusion about their regulatory status and limited clinical data supporting their use. We provide the general paediatrician with a brief review of cannabinoid biology, the literature regarding their use in children with drug resistant epilepsy, the current Health Canada and Canadian Paediatric Society recommendations and also the regulations from the physician regulatory bodies for each province and territory. Given the complexities of conducting research on Cannabis products for children with epilepsy, we also discuss outstanding research objectives that must be addressed to support Cannabis products as an accepted treatment option for children with refractory epilepsy.

To assess the relationship between lifetime, past-year, and frequent past-year cannabis use on use of other substances among youth in order to inform prevention initiatives.Data are from 27,900 youth aged 12-17 participating in the 2015-2016 National Surveys on Drug Use and Health. Multivariable multinomial logistic regression assessed the relationship between levels of youth cannabis use and past-year use of other substances compared to youth with no lifetime cannabis use.Prevalence of lifetime cannabis use among youth was 15.4%; 3.0% reported lifetime but not past-year use, 10.3% reported past-year use <200 days, and 2.1% reported past-year use ≥200 days. Past-year tobacco and alcohol use, and past-year misuse of prescription sedatives or tranquilizers, stimulants, and opioids were associated with increased adjusted relative risk ratios across all levels of cannabis use compared to youth reporting no lifetime cannabis use. Increased adjusted relative risk ratios across all levels of cannabis use were seen among youth aged 14-15 and 16-17 compared to 12-17 and among non-Hispanic blacks and Hispanics compared to non-Hispanic whites.Cannabis use is prevalent among youth and associated with other substance use. Efforts to scale up prevention programming and science-based messaging on risks of substance use are needed.

To assess, before legalization in Canada, whether parental cannabis use is associated with initiation of use in adolescent offspring or with use in young-adult offspring.Data were available in 2 longitudinal studies in Montréal, Canada. In AdoQuest, 1048 parents with children in grade 6 reported past-year cannabis use. Cannabis initiation among offspring was measured in grade 7, 9, and/or 11. In the Nicotine Dependence in Teens study, cannabis use data were available for 584 participants (mean age 24 years) and their parents (ie, 542 offspring-mother pairs, 438 offspring-father pairs). The association between parental and offspring cannabis use was estimated using multivariable logistic regression in both studies.In AdoQuest, grade 6 never-users were 1.8 times more likely to initiate cannabis during high school if their parents reported past-year use. In the Nicotine Dependence in Teens study, the aORs (95% CI) for past-year cannabis use among adult offspring were not different for "mother uses cannabis" (2.8 [1.4-5.8]) or "father uses cannabis" (2.1 [1.2-3.8]). Participants with 1 or 2 cannabis-using parents were 1.7 and 7.1 times more likely to use cannabis, respectively, than participants with non-using parents.To enable informed decision-making about their own cannabis use, parents need to be aware that children of cannabis users are more likely to use cannabis in adolescence and young adulthood.

Synthetic cannabinoid receptor agonists (SCRAs) are suggested to have increased potential to induce psychosis compared to natural cannabis (NC). In this review we synthesise current knowledge about the association of SCRA use with psychotic symptoms. Following a literature search we identified 2 toxicology reports, 4 case-control studies, 3 cross-sectional studies and 15 case reports. In each of the case reports, we identified the presence or absence of symptoms based on the items of the Postitive and Negative Syndrome Scele (PANSS). The toxicology reports highlighted the main presenting features as being toxic psychosis and delirium (40%), agitation (10%) and hallucinations (4-7%). The median age was 25 years, and around 80% cases were male. Cross-sectional studies reported that SCRA use was present in approximately 10-13% patients presenting to acute psychiatric services, and was often the cause of their presentation, and that psychotic symptoms were present in 15% patients attending emergency departments following SCRA use. Case-control studies reported that SCRA use was significantly associated with psychotic symptoms and that SCRA users had higher levels of positive psychotic symptoms than NC users. The case reports supported the association of SCRA use with a wide range of positive and negative psychotic symptoms as well as with self-harm, agitation and aggressive behaviour. SCRA use is relatively prevalent in patients with psychosis and may lead to psychotic symptoms in individuals with no past psychiatric history. Further work is required to understand the long term risks of SCRA use and optimal management strategies.

Alcohol and drug use and other health-risk behaviors tend to cluster together among adolescents and contribute a large amount of harm to both themselves and to others. This paper aims to characterize secondary school students based on their clusters of health-risk behaviors and identify factors determining class membership to these behavior-clusters.Data from a national school survey was used to identify clusters of alcohol and drug use and other health-risk behaviors among secondary school students aged 12-15 years using a latent class regression model. A multinomial logistic regression model was used to identify predictors of the cluster membership.A total of 25,566 students were included in the analysis, of which 88% were classified as having low-risk behaviors reporting only moderate alcohol use; 11% as having moderate-risk behaviors, such as driving under the influence of alcohol, fighting, carrying a weapon, and alcohol and tobacco use; and 0.6% as having high-risk behaviors, such as use of illicit drugs, particularly kratom and cannabis. Males, older students, those with a poor school performance, not living with parents, drug use by family members and peers, and having a low level of perceived disdain from their friends if they used drugs were significant risk factors for being in the moderate- and high-risk behavior classes.Alcohol, tobacco and drug use, as well as other health-risk behaviors such as fighting, are clustered in Thai secondary school students. This result highlights the importance of comprehensive prevention and education strategies, particularly for moderate to high-risk groups.

The bioSocial Cognitive Theory (bSCT) hypothesizes two pathways linking dimensions of impulsivity to substance use. The first predicts that the association between reward sensitivity and substance use is mediated by positive outcome expectancies. The second predicts that the relationship between rash impulsiveness and substance use is mediated by refusal self-efficacy. This model has received empirical support in studies of alcohol use. The present research provides the first application of bSCT to a cannabis treatment population and aims to extend its utility to understanding cannabis use and severity of dependence.273 patients referred for cannabis treatment completed a clinical assessment that contained measures of interest.A public hospital alcohol and drug clinic.The Sensitivity to Reward Scale, Dysfunctional Impulsivity Scale, Cannabis Expectancy Questionnaire, Cannabis Refusal Self-Efficacy Questionnaire and Severity of Dependence Scale-Cannabis were completed, along with measures of cannabis consumption.The bSCT model provided a good fit to the data for cannabis use and severity of dependence outcomes. The association between reward sensitivity and each cannabis outcome was fully mediated by positive cannabis expectancies and cannabis refusal self-efficacy. The relationship between rash impulsiveness and each cannabis outcome was fully mediated by cannabis refusal self-efficacy.Findings support the application of the bSCT model to cannabis use and dependence severity and highlight the important role of social cognitive mechanisms in understanding the association between impulsivity traits and these outcomes. The differential association of impulsivity traits to social cognition may assist targeted treatment efforts.

Background: Cannabis harms among Indigenous populations in Australia, New Zealand, Canada and the United States may be magnified by poorer health and heavy use. However, little direct evidence is available to evaluate cannabis' impacts. In communities in remote northern Queensland (Australia) where cannabis has become endemic, opportunities to support change were investigated. Methods: Opportunistically recruited participants (aged 15-49 years) discussed their cannabis use history in interviews in two waves of population sampling in Cape York (Queensland). Wave 1 included 429 people (235 males and 194 females); and wave 2 included 402 people (228 males and 174 females). Current users (used cannabis during the year before interview) described frequency of use, amount consumed, expenditure and dependence symptoms. Other substance use was recorded for 402 people at wave 2. Results: Wave 1: 69% reported lifetime use and 44% current use. Males (55%) were more likely than females (30%) to be current users (P < 0.001). Most (96%) current users described at least weekly use; nearly half (48%) were "heavy" users (≥6 cones/session at least once/week) and 77% met cannabis dependence criteria. Three communities spent up to $AUD14,200/week on cannabis, around $AUD2.0 million/year, or around 9% of community people's total income on cannabis. The majority (79%) of current users wanted to quit or reduce their cannabis use. Wave 2: no difference was observed in the proportion of lifetime (69%, |z| = 0.04, P = 0.968) or current cannabis users (39%, |z| = 1.39, P = 0.164); nor current use among males (71%, |z| = 0.91, P = 0.363) or females (62%, |z| = 0.36, P = 0.719). However, a significant reduction in current users by 15% (|z| = 2.36, P = 0.018) was observed in one community. Of 105 wave 1 current users re-assessed in 2, 29 (27%) had ceased use. These participants reported cost and family commitments as reasons to change and that social support and employment enabled abstinence. Current and lifetime cannabis use were closely associated with all other substance use, particularly tobacco and alcohol (both P > 0.001). Conclusions: High rates of heavy cannabis use in remote Australian Indigenous communities warrant action. Successful cessation among some individuals suggests that significant opportunities are available to support change even where cannabis use may be endemic.

Maternal cigarette smoking is a recognised risk factor for maternal and fetal morbidity and mortality and remains a significant problem in the Irish maternity system. Approximately 11% of Irish women will continue to smoke in pregnancy, despite awareness of the negative impact on their pregnancy. Although recommendations exist for the management of pregnant smokers, information on the antenatal care of Irish smokers in pregnancy has not been described. We reviewed the care given to smokers in a large urban maternity hospital.This is a retrospective cohort study of 100 consecutive smokers and 110 contemporaneous non-smokers who delivered at a large urban maternity hospital of over 8200 births per year in Oct-Nov 2017. Data were obtained from both electronic patient records and chart review to ensure comprehensive capture of outcomes.In general, mothers who smoked were younger (29yrs vs 33yrs p < 0.001) and of higher parity (1.4 vs. 1.0 p < 0.001) than non-smokers. They were less likely to have a planned pregnancy (44.4% vs 79.6%, p < 0.001) and less likely to have taken pre-conceptual folic acid (22.2% vs 58.3%, p < 0.001). These mothers also had a higher rate of history of illicit drug use, particularly cannabis (19.1% vs 0.9%, p < 0.001) and opiates (16.1% vs 0.9%, p < 0.001). Mental health issues were commoner in smokers with 36.3% describing depression, postnatal depression or bipolar disorder and 34.3% experiencing anxiety disorder or panic attacks. Smoking cessation advice was identified in only 36.5% of smokers and no smokers were referred for smoking cessation interventions. Two thirds of smokers were referred for an additional ultrasound, largely due to suspected fetal growth restriction. Infants of smoking mothers had lower mean birthweights (3.16 kg vs 3.47 kg p < 0.001) and mean birth centile (27th vs 47th p < 0.001) than non-smokers. Twenty eight percent of these infants were small for gestational age, an incidence significantly higher than non-smokers at 13% (p < 0.001).Maternal cigarette smoking appears to be a largely tolerated risk factor in the population studied, despite being associated with poor obstetric outcomes. We identified an absence of smoking cessation services and a lack of intervention and structure around care pathways.

Cannabis is the most commonly used recreational drug during pregnancy in the United States. This study aimed to describe the rate of cannabis dependence or abuse use during pregnancy and its effect on obstetrical and neonatal outcomes.A retrospective population-based cohort of births in the United States between 1999 and 2013 was created using data from the National Inpatient Sample. Births to mothers who reported cannabis dependence or abuse were identified using ICD-9 codes, and the effect on various obstetrical and neonatal outcomes was assessed using logistic regression, adjusting for relevant confounders (Canadian Task Force Classification II-2).A total of 12 578 557 births were included in our analysis. The incidence of cannabis abuse or dependence rose from 3.22 in 1000 births in 1999 to 8.55 in 1000 births in 2013 (P < 0.0001). Women reporting cannabis dependence or abuse were more likely to have a preterm premature rupture of membranes (OR 1.46; 95% CI 1.35-1.58), a hospital stay of >7 days (OR 1.17; 95% CI 1.11-1.23), and an intrauterine fetal demise (OR 1.50; 95% CI 1.39-1.62). Neonates born to exposed mothers had a higher risk of prematurity (OR 1.40; 95% CI 1.36-1.43) and growth restriction (OR 1.35; 95% CI 1.30-1.41).Cannabis use during pregnancy steadily increased over the study period. Users of cannabis during gestation were more likely to have adverse outcomes during delivery and require longer periods of hospitalization. Neonates born to exposed mothers were more likely to be born preterm and underweight.

More than four decades ago, the United States Surgeon General issued a warning regarding the medical problems of marijuana smoking, including cardiac toxicity. Since then, many reports have described atrial fibrillation, ventricular tachycardia, acute coronary syndromes, and cardiac arrest temporally related to marijuana use. The subjects were quite young, with no significant cardiovascular risk factors, with the only obvious trigger being marijuana use. Despite these strong signals, the drug is now legalized for recreational use in many states. We believe the time has come to conduct definitive studies about the safety of marijuana before this trend moves to the rest of the nation.

Evidence suggests that cannabis use may be associated with suicidality in adolescence. Nevertheless, very few studies have assessed this association in low- and middle-income countries (LMICs). In this cross-sectional survey, we investigated the association of cannabis use and suicidal attempts in adolescents from 21 LMICs, adjusting for potential confounders.Data from the Global school-based Student Health Survey was analyzed in 86,254 adolescents from 21 countries [mean (SD) age = 13.7 (0.9) years; 49.0% girls]. Suicide attempts during past year and cannabis during past month and lifetime were assessed. Multivariable logistic regression analyses were conducted.The overall prevalence of past 30-day cannabis use was 2.8% and the age-sex adjusted prevalence varied from 0.5% (Laos) to 37.6% (Samoa), while the overall prevalence of lifetime cannabis use was 3.9% (range 0.5%-44.9%). The overall prevalence of suicide attempts during the past year was 10.5%. Following multivariable adjustment to potential confounding variables, past 30-day cannabis use was significantly associated with suicide attempts (OR = 2.03; 95% CI: 1.42-2.91). Lifetime cannabis use was also independently associated with suicide attempts (OR = 2.30; 95% CI: 1.74-3.04).Our data indicate that cannabis use is associated with a greater likelihood for suicide attempts in adolescents living in LMICs. The causality of this association should be confirmed/refuted in prospective studies to further inform public health policies for suicide prevention in LMICs.

Background: The nascent cannabis industry is often challenged by a lack of guidance, unproven methodologies and conflicting legal challenges. The actual sampling and sample preparation of cannabis can be a difficult endeavor due the economic value, material complexity and heterogeneous nature of a plant based material. Objective: Examine the challenges of cannabis material sampling and sample processing as it relates to other similar materials. Method: In this paper, the complexity of sampling and sample preparation are reviewed for use in the cannabis industry. The mechanisms for sample processing are examined and compared for the best preparation techniques for targeted analytes in cannabis analysis. Results: Cryogenic grinding is one of the best methods for sample processing for the preservation of volatile compounds. Conclusions: Proper sampling techniques and procedures, including the use of standards, ensure homogeneity and improve analysis accuracy. Highlights: Methods of sample processing and preparation for cannabis plant material were examined to ensure homogeneity, accuracy and reproducibility.

In the current research, we examined the association of key risk and protective factors for gambling involvement from the domains of family environment, conduct problems/delinquency, substance use, and depressive psychopathology in a nationally representative sample. The sample was comprised of 13,291 young adults (ages 18-26; Meanage = 22.8) self-identifying as European American (n=9,939) or African American (n=3,335) who participated in Wave III (n = 15,170) of the restricted-use National Longitudinal Study of Adolescent to Adult Health. We used separate logistic regressions to study participation in specific gam bling categories (lottery games, casino-type games, other games). Childhood neglect, physical discipline, and current alcohol use was associated across each of the three gam bling categories. Our results also revealed differences between European American and African American subjects. Current cannabis use was associated with all three categories among African Americans, while current cigarette use was associated among European Americans for lottery games, and depression (female) was associated with other games. We also applied multinomial logistic regression to study gambling involvement based on the number of gam bling categories that the participant engaged in 2 or more (referent), only 1, or none at all. Our results revealed that delinquency/conduct symptoms (AOR=0.83) along with cannabis use (African American; AOR =0.66), cigarette use (European American; AOR =0.83), current alcohol use (AOR=0.66) were associated with gambling in two categories vs. gambling in one category. Childhood physical discipline (AOR=0.75) and childhood neglect (AOR=0.75) were associated with gam bling in two categories vs. no gambling. Further are needed to investigate the developmental pathways leading to increased gam bling involvement among African American and European American adolescents and young adults.

Epilepsy is considered to be one of the most common non-communicable neurological diseases especially in low to middle-income countries. Approximately one-third of patients with epilepsy have seizures that are resistant to antiepileptic medications. Clinical trials for the treatment of medically refractory epilepsy have mostly focused on new drug treatments, and result in a significant portion of subjects whose seizures remain refractory to medication. The off-label use of cannabis sativa plant in treating seizures is known since ancient times. The active ingredients of this plant are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), the latter considered safer and more effective in treating seizures, and with less adverse psychotropic effects. Clinical trials prior to two years ago have shown little to no significant effects of cannabis in reducing seizures. These trials seem to be underpowered, with a sample size less than 15. In contrast, more recent studies that have included over 100 participants showed that CBD use resulted in a significant reduction in seizure frequency. Adverse effects of CBD overall appear to be benign, while more concerning adverse effects (e.g., elevated liver enzymes) improve with continued CBD use or dose reduction. In most of the trials, CBD is used in adjunct with epilepsy medication, therefore it remains to be determined whether CBD is itself antiepileptic or a potentiator of traditional antiepileptic medications. Future trials may evaluate the efficacy of CBD in treating seizures due to specific etiologies (e.g., post-traumatic, post-stroke, idiopathic).

Cannabis use disorder (CUD) is the most common illicit substance use disorder and individuals with CUD have high rates of comorbid anxiety disorders. Comorbidity between CUD and anxiety disorders is of public health relevance given that although motivation enhancement therapy (MET) combined with cognitive-behavioral therapy (CBT) is an efficacious intervention for CUD, outcomes are worse for patients with elevated anxiety. The current study tested the acceptability and efficacy of the integration of a transdiagnostic anxiety CBT (i.e., treatment of patients with any anxiety disorder) with MET-CBT (integrated cannabis and anxiety reduction treatment, or ICART) for CUD compared to MET-CBT alone. Treatment-seeking cannabis users (56.4% male, Mage = 23.2, 63.3% non-Hispanic White) with CUD and at least one comorbid anxiety disorder were randomly assigned to ICART (n = 27) or MET-CBT (n = 28). Patients in the ICART condition attended significantly more treatment sessions than those in the MET-CBT condition. Patients in the ICART condition were more likely to be abstinent post-treatment than those in MET-CBT. Further, treatment produced decreases in cannabis use and related problems. Notably, therapy type did not moderate the impact of treatment on frequency of use and related problems. Together, these data suggest that ICART may be at least as efficacious as a gold-standard psychosocial CUD treatment, MET-CBT, for a difficult-to-treat subpopulation of cannabis users.

Cannabis consumption produces psychopathology, in some cases psychotic episodes, which are of our interest in this work. However, the relationship between cannabis use and psychosis has not been fully elucidated. The objectives of this work are to (1) review the current state of knowledge on the association of cannabis use with the risk of the development of psychosis or psychotic symptoms in people without schizophrenia and (2) assess the consistency of the hypothesis that cannabis use is associated with increased risk of psychosis in people without schizophrenia.This work included research done in humans until May 2018 with the keywords 'cannabis' and 'psychosis', published in English and Spanish, in the PubMed database.In all, 66 papers were analyzed, of which 23 were cohort trials and 43 were reviews.Cannabis use doubles the risk of developing psychosis in vulnerable people. There even exists a relationship regarding the dose used and the age of first use. Gene-environment interactions that modulate the association between cannabis use and the presence of psychosis have also been described.

Relatively little is known about factors that may lead to the development of a substance use disorder (SUD), across a range of drug classes. This study aimed to identify factors that predict the likelihood of transition from use to SUD and the speed with which this may occur at the population level, with a focus on the impact of pre-existing mental disorders.Data were collected as part of the 2007 Australian National Survey of Mental Health and Wellbeing, a nationally representative survey of 8841 Australian adults. A series of discrete time survival analyses were undertaken on data pertaining to the age of onset of use and symptoms of use disorder, for alcohol, cannabis, sedatives, stimulants, and opioids, as well as the impact of pre-existing mood and anxiety disorders on the likelihood of developing a SUD.Lifetime cumulative probability estimates indicated that 50.4% of stimulant, 46.6% of opioid, 39% of sedative, 37.5% of alcohol, and 34.1% of cannabis users would develop a SUD on those substances, within an estimated 14, 12, 8, 30, and 23 years after onset respectively. Pre-existing mental disorders were significantly associated with increased risk of developing a SUD for alcohol, cannabis and stimulant use disorder.The relative speed associated with the transition from use to SUD emphasizes the narrow window of time available to intervene, underscoring the urgency of early identification of mental health conditions and the timely provision of appropriate evidence-based interventions, which could potentially prevent the development of secondary SUDs.

Δ9-tetrahydrocannabinol (THC) consumption during adolescence is reported to be a risk factor for the appearance of psychiatric disorders later in life. The interaction between genetic or environmental events and cannabinoid exposure in the adolescent period can also contribute to exacerbate behavioural deficits in adulthood. Here we investigate the effects of THC treatment as well as the consequences of concomitant THC and stress exposure during adolescence in the extinction of fear memory in adult mice. Adolescent mice treated with THC and exposed to stress exhibit impaired cued fear extinction in adulthood. However, no effect was observed in animals exposed to these two factors separately. Notably, resistance to fear extinction was associated with decreased neuronal activity in the basolateral amygdala (BLA) and the infralimbic prefrontal cortex, suggesting a long-term dysregulation of the fear circuit. These changes in neuronal activation were paralleled with structural plasticity alterations. Indeed, an increase of immature dendritic spines in pyramidal neurons of the BLA was revealed in mice simultaneously exposed to THC and stress. Corticosterone levels were also enhanced after the cued fear conditioning session in the same experimental group. These results show that an interaction between cannabis exposure and stress during adolescence may lead to long-term anxiety disorders characterized by the presence of pathological fear.

Diabetes and aging are risk factors for cognitive impairments after chronic cerebral hypoperfusion (CCH). Cannabidiol (CBD) is a phytocannabinoid present in the Cannabis sativa plant. It has beneficial effects on both cerebral ischemic diseases and diabetes. We have recently reported that diabetes interacted synergistically with aging to increase neuroinflammation and memory deficits in rats subjected to CCH. The present study investigated whether CBD would alleviate cognitive decline and affect markers of inflammation and neuroplasticity in the hippocampus in middle-aged diabetic rats submitted to CCH. Diabetes was induced in middle-aged rats (14 months old) by intravenous streptozotocin (SZT) administration. Thirty days later, the diabetic animals were subjected to sham or CCH surgeries and treated with CBD (10 mg/kg, once a day) during 30 days. Diabetes exacerbated cognitive deficits induced by CCH in middle-aged rats. Repeated CBD treatment decreased body weight in both sham- and CCH-operated animals. Cannabidiol improved memory performance and reduced hippocampal levels of inflammation markers (inducible nitric oxide synthase, ionized calcium-binding adapter molecule 1, glial fibrillary acidic protein, and arginase 1). Cannabidiol attenuated the decrease in hippocampal levels of brain-derived neurotrophic factor induced by CCH in diabetic animals, but it did not affect the levels of neuroplasticity markers (growth-associated protein-43 and synaptophysin) in middle-aged diabetic rats. These results suggest that the neuroprotective effects of CBD in middle-aged diabetic rats subjected to CCH are related to a reduction in neuroinflammation. However, they seemed to occur independently of hippocampal neuroplasticity changes.

Due to size and accessibility, most information about the habenula is derived from rodent studies. To better understand the molecular signature of the habenula we characterized the genes that have high expression in the habenula. We compared anatomical expression profiles of three normal adult human brains and four fetal brains. We used gene set enrichment analyses to determine if genes annotated to specific molecular functions, cellular components, and biological processes are enriched in the habenula. We also tested gene sets related to depression and addiction to determine if they uniquely involve the habenula. As expected, we observed high habenular expression of GPR151, nicotinic cholinergic receptors, and cilia-associated genes (medial division). Genes identified in genetic studies of smoking and associated with nicotine response were enriched in the habenula. Genes associated with major depressive disorder did not have enriched expression in the habenula but genes negatively correlated with hedonic well-being were, providing a link to anhedonia. We observed enrichment of genes associated with diseases that are comorbid with addictions (hematopoiesis, thrombosis, liver cirrhosis, pneumonia, and pulmonary fibrosis) and depression (rheumatoid arthritis, multiple sclerosis, and kidney disease). These inflammatory diseases mark a neuroimmune signature that is supported by genes associated with mast cells, acute inflammatory response, and leukocyte migration. We also found enrichment of cytochrome p450 genes suggesting the habenula is uniquely sensitive to endogenous and xenobiotic compounds. Our results suggest the habenula receives negative reward signals from immune and drug processing molecules. This is consistent with the habenular role in the "anti-reward" system and suggests it may be a key bridge between autoimmune disorders, drug use, and psychiatric diseases.

Cannabis use has increased over the past several years as some countries have legalized its use for treatment of certain medical conditions and/or for recreational use. Thus, concerns have risen about potential adverse health effects. Increasing number of reports have associated cannabis use with serious cardiovascular (CV) complications. Furthermore, there appears to be a likeness in the harmful health effects, especially on the CV and respiratory systems, of cannabis smoking to those of tobacco smoking.to review the CV effects of cannabis use and compare them with those of tobacco use.Articles were reviewed that were published in the English literature reporting on cannabis and cannabinoid pharmacology and their effects on the CV system and their attendant consequences. Emphasis was also placed on articles reporting on cannabis use in adolescents, exposure to secondhand smoke, its effect on exercise and finally its inter-relationship and similarities with tobacco use.With growing cannabis use, increasing number of reports have emerged associating marijuana use with serious and life-threatening CV complications, including acute coronary syndromes, potentially lethal cardiac arrhythmias and ischemic strokes. There are certain similarities of the deleterious CV and respiratory effects of cannabis smoking with those of tobacco smoking. Despite the difference in the active ingredients (tetrahydrocannabinol vs nicotine), each substance produces a plethora of chemicals when smoked and these are largely identical; furthermore, due to different modes of smoking, cannabis chemicals are retained in the body for a longer time. Of course, concomitant tobacco and cannabis smoking is a perplexing factor in isolating damages specifically pertaining to cannabis use, while the health risk is additive. Although the mechanisms producing CV harm may be somewhat different between these two substances, the outcome appears similar, or even worse, as the effects may emerge at a younger age.There is an increasing concern that, apart from the mental health problem with cannabis smoking, societies may be facing another wave of a déjà vu / déjà vécu phenomenon similar to the tobacco smoking story.

Currently 29 states in the United States along with the District of Columbia have legalized cannabis in some forms. There is a paucity of data on the impact of legalization of cannabis use on hospitalizations due to cyclic vomiting syndrome (CVS).To study the trends in CVS-related hospitalizations and cannabis use in CVS in relation to legalization of recreational cannabis use in Colorado.All hospital admissions in Colorado between 2010 -2014 with the diagnosis of CVS were identified using the Colorado State Inpatient Database (SID). Five-year trends in CVS-related hospitalizations along with the cannabis use were analyzed. Multivariate logistic regression analysis was performed to determine predictors of cannabis use in CVS.There was a significant increase in CVS- related hospitalizations by 46% from 806 in 2010 to 1,180 in 2014 when CVS was included as all-listed diagnoses (P<0.001). The overall prevalence of cannabis use in CVS (13% with CVS as primary diagnosis and 17% with CVS as all-listed diagnoses) was much higher than non-CVS related hospitalizations (1.7%) (P<0.001 for both comparisons). Cannabis use increased dramatically in both CVS and non-CVS related hospitalizations following legalization of cannabis for recreational use in 2012.Our study shows a significant increase in CVS-related hospitalizations concomitant with an increase in cannabis use with its liberalization in Colorado. Future studies on the relationship between cannabis use and hyperemesis are warranted, especially with its ongoing legalization in the US. This article is protected by copyright. All rights reserved.

Cannabis use is becoming increasingly popular as a growing number of states pass legislation to legalize cannabis and cannabis-derived products for recreational and/or medical purposes. Given the widespread use of cannabis, it is critical to understand the neural consequences related to cannabis use. In this review, we focus on evidence from functional magnetic resonance imaging studies that document acute and residual alterations in brain function during tasks spanning a variety of cognitive domains: executive function, attention and working memory, memory, motor skills, error monitoring, and reward and affective processing. Although it is clear that cannabis affects brain function, the findings are somewhat inconsistent; variables that potentially affect study outcomes are outlined, including a discussion of the impact of chronological age and age of cannabis onset as well as length of abstinence at the time of assessment, which are important considerations when measuring cannabis use patterns. Inherent differences between recreational/adult cannabis use versus use for medical purposes are also discussed, given their importance to public policy decisions.

New concepts are reviewed in Cannabis systematics, including phylogenetics and nomenclature. The family Cannabaceae now includes Cannabis, Humulus, and eight genera formerly in the Celtidaceae. Grouping Cannabis, Humulus, and Celtis actually goes back 250 years. Print fossil of the extinct genus Dorofeevia (=Humularia) reveals that Cannabis lost a sibling perhaps 20 million years ago (mya). Cannabis print fossils are rare (n=3 worldwide), making it difficult to determine when and where she evolved. A molecular clock analysis with chloroplast DNA (cpDNA) suggests Cannabis and Humulus diverged 27.8 mya. Microfossil (fossil pollen) data point to a center of origin in the northeastern Tibetan Plateau. Fossil pollen indicates that Cannabis dispersed to Europe by 1.8-1.2 mya. Mapping pollen distribution over time suggests that European Cannabis went through repeated genetic bottlenecks, when the population shrank during range contractions. Genetic drift in this population likely initiated allopatric differences between European Cannabis sativa (cannabidiol [CBD]>Δ9-tetrahydrocannabinol [THC]) and Asian Cannabis indica (THC>CBD). DNA barcode analysis supports the separation of these taxa at a subspecies level, and recognizing the formal nomenclature of C. sativa subsp. sativa and C. sativa subsp. indica. Herbarium specimens reveal that field botanists during the 18th-20th centuries applied these names to their collections rather capriciously. This may have skewed taxonomic determinations by Vavilov and Schultes, ultimately giving rise to today's vernacular taxonomy of "Sativa" and "Indica," which totally misaligns with formal C. sativa and C. indica. Ubiquitous interbreeding and hybridization of "Sativa" and "Indica" has rendered their distinctions almost meaningless.

Background: Medical cannabis has been available in the State of Minnesota since July 2015 through the Minnesota Medical Cannabis Program (MMCP). Objectives: Our study aimed to delineate oncology providers' views on medical cannabis, identify barriers to patient enrollment, and assess clinicians' interest in a clinical trial of medical cannabis in patients with stage IV cancer. Methods: From June to August 2017, we distributed a 14-question survey to Minnesota oncology physicians, advanced practice nurses, and physician assistants who care for adults and children with cancer. Descriptive analyses for each question were provided for all survey respondents. Results: Of the 529 eligible survey participants, 153 (29%) responded to our survey; 68 respondents were registered with the MMCP. Most identified themselves as a medical oncologist or medical oncology nurse practitioner/physician assistant (n=125, 82%), and most practiced in a community setting (n=102, 67%). Overall, 65% of respondents supported the use of medical cannabis. Perceived cost and inadequate research were the highest barriers to MMCP patient enrollment. The lowest barriers included lack of health group support for allowing certification of patients and risk of social stigma. Of all respondents, 36% lacked confidence in discussing the risks and benefits of medical cannabis, and 85% wanted more education. Conclusions: Although support for cannabis use in the cancer setting is growing, significant barriers remain. This study illustrates a clear need to give clinicians both data and education to guide their discussions about the benefits, risks, and cost considerations of using medical cannabis for cancer-related symptoms.

N-acetylcysteine, a sulphur-containing amino acid for the treatment of paracetamol overdose and chronic obstructive pulmonary disease, is a widely available off-the-shelf oral antioxidant supplement in many countries. With the potential to modulate several neurological pathways, including glutamate dysregulation, oxidative stress, and inflammation that can be beneficial to the brain functions, N-acetylcysteine is being explored as an adjunctive therapy for many psychiatric conditions. This narrative review synthesises and presents the current evidence from systematic reviews, meta-analyses, and latest clinical trials on N-acetylcysteine for addiction and substance abuse, schizophrenia, obsessive-compulsive and related disorders, and mood disorders. Good evidence exists to support the use of N-acetylcysteine as an adjunct treatment to reduce the total and negative symptoms of schizophrenia. N-acetylcysteine also appears to be effective in reducing craving in substance use disorders, especially for the treatment of cocaine and cannabis use among young people, in addition to preventing relapse in already abstinent individuals. Effects of N-acetylcysteine on obsessive-compulsive and related disorders, as well as on mood disorders, remain unclear with mixed reviews, even though promising evidence does exist. Larger and better-designed studies are required to further investigate the clinical effectiveness of N-acetylcysteine in these areas. Oral N-acetylcysteine is safe and well tolerated without any considerable adverse effects. Current evidence supports its use as an adjunctive therapy clinically for psychiatric conditions, administered concomitantly with existing medications, with a recommended dosage between 2000 and 2400 mg/day.

Evidence from diverse areas of medicine (e.g., cardiovascular disease, diabetes) indicates that healthcare providers (HCPs) often do not adhere to clinical practice guidelines (CPGs) despite a clear indication to implement recommendations-a phenomenon commonly termed clinical inertia. There are a variety of reasons for clinical inertia, but HCP-related factors (e.g., knowledge, motivation, agreement with guidelines) are the most salient and amenable to intervention aimed to improve adherence. CPGs have been developed to support the safe and effective prescription of opioid medication for the management of chronic non-cancer pain. The extent of physician uptake and adherence to such guidelines is not yet well understood. The purpose of this review is to synthesize the published evidence about knowledge, attitudes, beliefs, and practices that HCPs hold regarding the prescription of opioids for chronic non-cancer pain.An experienced information specialist will perform searches of CINAHL, Embase, MEDLINE, and PsycINFO bibliographic databases. The Cochrane library, PROSPERO, and the Joanna Briggs Institute will be searched for systematic reviews. Searches will be performed from inception to the present. Quantitative and qualitative study designs that report on HCP knowledge, attitudes, beliefs, or practices in North America will be eligible for inclusion. Studies reporting on interventions to improve HCP adherence to opioid prescribing CPGs will also be eligible for inclusion. Two trained graduate-level research assistants will independently screen articles for inclusion, perform data extraction, and perform risk of bias and quality assessment using recommended tools. Confidence in qualitative evidence will be evaluated using the Grades of Recommendation, Assessment, Development, and Evaluation-Confidence in the Evidence from Qualitative Reviews (GRADE-CERQual) approach. Confidence in quantitative evidence will be assessed using the GRADE approach.The ultimate goal of this work is to support interventions aiming to optimize opioid prescribing practices in order to prevent opioid-related morbidity and mortality without restricting a HCP's ability to select the most appropriate treatment for an individual patient.PROSPERO CRD42018091640 .

More than fifty percent of all new patient visits to pediatric gastroenterology clinics consult for functional abdominal pain disorders (FAPDs). In 2005, a technical report of the American Academy of Pediatrics and the North American Pediatric Gastroenterology, Hepatology and Nutrition society (NASPGHAN) found limited or inconclusive evidence for most therapeutic interventions for this group of disorders. The report did not include studies on herbs and spices. Since then, there has been an increasing interest in the use of complementary and alternative medicine (CAM) for the treatment of chronic pain disorders in children. About 40% of parents of pediatric gastroenterology patients have utilized CAM. This review evaluated the published literature on the effectiveness of CAM, specifically the use of herbs and spices, for the treatment of FAPDs. We found little evidence for most of the commonly used herbs and spices. Despite its common use, research on the efficacy, safety, and optimal dosage remains limited. There is evidence to suggest the benefit of peppermint oil and STW 5 for the treatment of FAPDs in children. The paucity of data on most therapies underscores the need for large clinical trials to assess their efficacy.

While controversial, cannabis use is common, and often begins in adolescence. In Australia and the Netherlands, cannabis use is understood and legislated within a harm-minimisation framework. In Australia it is illegal to purchase or consume cannabis. Cannabis use in the Netherlands is illegal, except in licensed coffee shops where the sale and consumption of small amounts (5 g) are permitted.Secondary school aged children in Victoria, Australia and the Netherlands were surveyed using the same culturally adapted questionnaire, designed to measure community rates of substance use and risk factors. Youth cannabis use and predictors of use were compared between the two countries.Similar levels of cannabis use in the last month were reported in Australia and the Netherlands (4.5%), with slightly lower use amongst girls, compared to boys. Common predictors of use were found in both the Australian and Netherlands sample.The findings suggest that interventions that effectively target similar risk factors to reduce or prevent cannabis use may have applications cross-nationally.

Cannabinoid drugs are widely used as analgesics, but experimental pain studies have produced mixed findings. The analgesic properties of cannabinoids remain unclear.To conduct a systematic review and meta-analysis of the association between cannabinoid drug administration and experimental pain outcomes in studies of healthy adults.A systematic search of PubMed, EMBASE, MEDLINE, PsycINFO, and CINAHL was conducted from the inception of each database to September 30, 2017. Studies were eligible for inclusion if they met criteria, including healthy participants and an experimentally controlled administration of any cannabinoid preparation in a quantified dose. Studies that used participants with chronic pain were excluded. Data extracted included study characteristics, cannabinoid types and doses, sex composition, and outcomes. Study quality was assessed using a validity measure previously established in published reviews. Random-effects meta-analyses were used to pool data and generate summary estimates.Experimental pain threshold, pain tolerance, pain intensity, pain unpleasantness, and mechanical hyperalgesia.Eighteen placebo-controlled studies (with 442 participants) were identified. Of the 442 participants, 233 (52.7%) were male and 209 (47.3%) were female. For sample ages, 13 (72%) of the 18 studies reported a mean sample age (26.65 years), 4 (22%) reported a range, and 1 (6%) reported a median value. The search yielded sufficient data to analyze 18 pain threshold comparisons, 22 pain intensity comparisons, 9 pain unpleasantness comparisons, 13 pain tolerance comparisons, and 9 mechanical hyperalgesia comparisons. Cannabinoid administration was associated with small increases in pain threshold (Hedges g = 0.186; 95% CI, 0.054-0.318; P = .006), small to medium increases in pain tolerance (Hedges g = 0.225; 95% CI, 0.015-0.436; P = .04), and a small to medium reduction in the unpleasantness of ongoing experimental pain (Hedges g = 0.288; 95% CI, 0.104-0.472; P = .002). Cannabinoid administration was not reliably associated with a decrease in experimental pain intensity (Hedges g = 0.017; 95% CI, -0.120 to 0.154; P = .81) or mechanical hyperalgesia (Hedges g = 0.093; 95% CI, -0.059 to 0.244; P = .23). The mean quality rating across studies was good.Cannabinoid drugs may prevent the onset of pain by producing small increases in pain thresholds but may not reduce the intensity of experimental pain already being experienced; instead, cannabinoids may make experimental pain feel less unpleasant and more tolerable, suggesting an influence on affective processes. Cannabis-induced improvements in pain-related negative affect may underlie the widely held belief that cannabis relieves pain.

Researchers have increasingly studied shyness, social anxiety, and social anxiety disorder (SAD) as potential precursors of substance use.The objective of this study was to review the relationships between these variables and tobacco use, alcohol use, and cannabis/drug use in normative adolescent populations and the extent to which these associations differ by gender.A systematic search in PsycINFO and PubMed was conducted, reference screening was performed, and five experts were consulted.Fifty articles published between 1980 and 2016 were included for review. Shyness was frequently associated with lower use of tobacco, alcohol, and cannabis/drug. Similar findings emerged for social anxiety. In contrast, SAD tended to be associated with higher use of tobacco and cannabis/drug, although the association between SAD and the use of alcohol appeared inconclusive. Furthermore, limited evidence suggests that shy females use less tobacco than shy males and that males with social anxiety use less drugs than socially anxious females.In conclusion, these results highlight that shyness, social anxiety, and SAD may exert different effects on substance use. Higher use of substances among adolescents suffering from a SAD may be explained, among other possibilities, by a self-medication mechanism. While all adolescents should benefit from prevention efforts targeted at substance use, a systematic screening for substance use disorders during the clinical evaluation that precedes SAD treatments is advised.

1. This study was conducted to determine the effects of raw and heat-treated hempseed (HHS, Cannabis sativa L.) on performance, egg quality and antioxidant activity in laying hens. 2. A total of 108 laying hens, aged 36 weeks, were divided into three treatment groups with 12 replicates and each replicate contained three laying hens. The treatments were as follows: (1) Control (no hempseed), (2) 15% raw hempseed (RHS) in diet and (3) 15% HHS in the diet. Experiments lasted for 12 weeks. 3. Feed intake of the RHS group was lower than those of the control and HHS groups. Egg weight, egg mass, shell weight, shell surface area and shell thickness of the HHS group were significantly (P < 0.05) higher than that of the RHS group. Roche (DSM) colour fan values of the RHS group were higher than that of the HHS group (P < 0.01). 4. Palmitic, palmitoleic and oleic acids of egg yolk were significantly (P < 0.05) decreased in the RHS and HHS groups; however, linoleic, α-linolenic and docosahexaenoic acids (DHA) of egg yolk increased (P < 0.05) for both treatment diets compared to the control group. 5. Both RHS and HHS supplementation to layer diets did not influence malondialdehyde (MDA) and superoxide dismutase (SOD) activity and blood lipid profile. 6. It was concluded that HHS was superior in improving the egg quality of laying hens as compared to the RHS.

AimsPrevious research has found links between cyberbullying victimisation and internalising and externalising problems among adolescents. However, little is known about the factors that might moderate these relationships. Thus, the present study examined the relationships between cyberbullying victimisation and psychological distress, suicidality, self-rated poor mental health and substance use among adolescents, and tested whether parent-child relationship and child's sex would moderate these relationships.Self-report data on experiences of cyberbullying victimisation, self-rated poor mental health, psychological distress, suicidality and substance use were derived from the 2013 Ontario Student Drug Use and Health Survey, a province-wide school-based survey of students in grades 7 through 12 aged 11-20 years (N = 5478). Logistic regression models adjusted for age, sex, ethnicity, subjective socioeconomic status and involvement in physical fighting, bullying victimisation and perpetration at school.Cyberbullying victimisation was associated with self-rated poor mental health (adjusted odds ratio (OR) 2.15; 95% confidence interval (CI) 1.64-2.81), psychological distress (OR 2.41; 95% CI 1.90-3.06), suicidal ideation (OR 2.38; 95% CI 1.83-3.08) and attempts (OR 2.07; 95% CI 1.27-3.38), smoking tobacco cigarette (OR 1.96; 95% CI 1.45-2.65), cannabis use (OR 1.82; 95% CI 1.32-2.51), and binge drinking (OR 1.44; 95% CI 1.03-2.02). The association between cyberbullying victimisation and psychological distress was modified by parent-child relationship and child's sex (three-way interaction term p < 0.05). The association between cyberbullying victimisation and psychological distress was much stronger among boys who have a negative relationship with their parents.Findings suggest that cyberbullying victimisation is strongly associated with psychological distress in most adolescents with the exception of males who get along well with their parents. Further research using a longitudinal design is necessary to disentangle the interrelationship among child's sex, parent-child relationship, cyberbullying victimisation and mental health outcomes among adolescents in order to improve ongoing mental health prevention efforts.

If pulmonary complications of tobacco smoking are well documented, those associated with cannabis use are less known.Systematic literature review of data on pneumothorax and lung emphysema in cannabis users.Medline, on the period 1980-2018 with the following keywords cannabis or marijuana and pneumothorax or emphysema, limits "title/abstract". Among 97 articles, 42 abstracts have given use to a dual reading to select 20 studies.Eighteen case reports (8 with SP) showed bullae in the upper lobes in combined cannabis and tobacco smokers (CS) and in the 2 cannabis only smokers (COS). The risk of SP was increased in CS, but not in COS. In patients less than 35-years old presenting with SP, the incidence of bullae on thoracic computed tomography (CT) was higher in CS than in tobacco only smokers (TOS). CT in patients with SP showed no significant difference as regards of the prevalence, location and type of emphysema between CS and TOS. Proportion of low lung density areas was higher in CS than in non-smokers (NS), but was similar in TOS and NS.These results suggest a cumulative toxic effect of tobacco and cannabis on the risk of SP and lung emphysema.

Cannabis possesses a rich spectrum of phytochemicals i.e. cannabinoids, terpenes and phenolic compounds of industrial and medicinal interests. Most of these high-value plant products are synthesised in the disk cells and stored in the secretory cavity in glandular trichomes. Conventional trichome analysis was so far based on optical microscopy, electron microscopy or extraction based methods that are either limited to spatial or chemical information. Here we combine both information to obtain the spatial distribution of distinct secondary metabolites on a single-trichome level by applying Coherent anti-Stokes Raman scattering (CARS), a microspectroscopic technique, to trichomes derived from sepals of a drug- and a fibre-type.Hyperspectral CARS imaging in combination with a nonlinear unmixing method allows to identify and localise Δ9-tetrahydrocannabinolic acid (THCA) in the secretory cavity of drug-type trichomes and cannabidiolic acid (CBDA)/myrcene in the secretory cavity of fibre-type trichomes, thus enabling an easy discrimination between high-THCA and high-CBDA producers. A unique spectral fingerprint is found in the disk cells of drug-type trichomes, which is most similar to cannabigerolic acid (CBGA) and is not found in fibre-type trichomes. Furthermore, we differentiate between different cell types by a combination of CARS with simultaneously acquired two-photon fluorescence (TPF) of chlorophyll a from chloroplasts and organic fluorescence mainly arising from cell walls enabling 3D visualisation of the essential oil distribution and cellular structures.Here we demonstrate a label-free and non-destructive method to analyse the distribution of secondary metabolites and distinguish between different cell and chemo-types with high spatial resolution on a single trichome. The record of chemical fingerprints of single trichomes offers the possibility to optimise growth conditions as well as guarantee a direct process control for industrially cultivated medicinal Cannabis plants. Moreover, this method is not limited to Cannabis related issues but can be widely implemented for optimising and monitoring all kinds of natural or biotechnological production processes with simultaneous spatial and chemical information.

To examine the longitudinal patterns of amphetamine use over twenty years from adolescence to the mid-thirties; and identify adolescent antecedents of future problematic patterns of use.Ten-wave longitudinal study following participants from age 15 to age 35 in Victoria, Australia. Participants (N = 1755; 47% males) first enrolled in the Victoria Adolescent Health Cohort Study in 1992.Outcome: Self-reported frequency of amphetamine use.Gender, depression and anxiety, peer alcohol and tobacco use; self-reported alcohol, tobacco and cannabis use, self-reported adolescent antisocial behavior.Three different longitudinal patterns were identified: Non-user (83.7%); Occasional user (14.5%); Regular user (1.8%). Among the two user patterns, amphetamine use was commonly initiated in late teenage years or early 20s, peaked at mid-20s, and declined substantially by mid-30s. Participants who used cannabis and had smoking peers during adolescence were at significantly more likely to become an occasional or regular user (p <  .05).Regular cannabis use and peer tobacco use during adolescence were the two strongest predictors of a longitudinal pattern of regular amphetamine use in the mid-30s. This suggests that prevention programs could be implemented around or before mid-adolescence and interventions to reduce amphetamine harms focus on high-risk individuals in their 20s when amphetamine use was at its peak.

Cannabis use is increasing due to recent legislative changes. In addition, cannabis is often used in conjunction with alcohol. The airway epithelium is the first line of defense against infectious microbes. Toll-like receptors (TLR) recognize airborne microbes and initiate the inflammatory cytokine response. How cannabis use in conjunction with alcohol affects pulmonary innate immunity mediated by TLRs is unknown.Samples and data from an existing cohort of individuals with alcohol use disorders (AUDs), along with samples from additional participants with cannabis use alone and with AUD were utilized. Subjects were categorized into the following groups: no alcohol use disorder (AUD) or cannabis use (Control) (n=46), AUD only (n=29), Cannabis use only (n=39) and AUD and Cannabis use (n= 29). The participants underwent bronchoscopy with bronchoalveolar lavage (BAL) and airway epithelial brushings. We measured IL-6, IL-8, TNF⍺ and IL-10 levels in BAL fluid, and performed real time PCR for TLR1-9 on the airway epithelial brushings.We found significant increases in TLR2 with AUD alone, cannabis use alone and cannabis use with AUD compared to control. TLR5 was increased in cannabis users compared to control, TLR6 was increased in cannabis users and cannabis users with AUD compared to control, TLR7 was increased in cannabis users compared to control, and TLR9 was increased compared to control. In terms of cytokine production, IL-6 was increased in cannabis users compared to control. IL-8 and IL-10 were increased in AUD only.AUD and cannabis use have complex effects on pulmonary innate immunity that promote airway inflammation.

Prescription opioid use and opioid related deaths continue to increase nationwide. Several states have adopted legislation allowing for recreational use of cannabis. Little is known about how recreational cannabis laws impact compliance in chronic pain patients who have been prescribed opioid therapy. The goals of this study were to (1) retrospectively assess the effect of cannabis use on compliance with opioid therapy in a high-risk patient population and (2) determine the impact of legalization of recreational cannabis on patients prescribed therapeutic opioids.We conducted a retrospective cohort study on results from a "high-risk" urine drug testing panel. Results from 1 year before and 1 year after initiation of recreational cannabis legislation were analyzed. This testing panel included qualitative assays for cannabinoids and 9 other common drugs of abuse in addition to a quantitative LC-MS/MS assay for 23 different opioids and metabolites. Opioid compliance was assigned by reviewing pathologists' interpretations.In the pre-legalization period, 1776 panels were performed, and in the post-legalization, 1648 panels were performed. An increase (6%) in the rate of positive cannabinoids screening results was observed after legalization of recreational cannabis; however, the overall compliance rate was consistent.The results of this study suggest that legalization of recreational cannabis does not affect compliance rate in patients treated with opioid therapy for chronic pain.

To examine national trends and contributing factors of cannabis-associated emergency department visits in the United States.This pooled serial cross-sectional study used a hierarchical multivariable analysis on emergency department visit adjusting for year, patient and hospital characteristics. We analyzed 2006 to 2014 National Emergency Department Sample data that identified cannabis-associated emergency department visits among patients aged 12 years or older (n = 265,128).Cannabis-associated emergency department visits per 100,000 emergency department discharges increased monotonically (annually by 7%). As compared with privately insured patients, Medicare, and Medicaid, uninsured patients were over 40% more likely to visit emergency department. The age group 12 to 17 had the highest risk of emergency department visits and the risk monotonically declined as the age increased. Hospitals in the South region showed the highest cannabis-associated emergency department utilization, yet trends of cannabis-associated emergency department visits increased in the West region from 15.4% to 26% over time.Cannabis-associated emergency department visits increase monotonically over time. Although vulnerable persons were identified, additional policy or regional factors should explore risks of emergency department visits associated with cannabis use.

Low back pain (LBP) occurs in many patients with fibromyalgia (FM). The current study aimed to assess the possible pain and function amelioration associated with medical cannabis therapy (MCT) in this setting.31 patients were involved in an observational cross-over study. The patients were screened, treated with 3 months of standardised analgesic therapy (SAT): 5 mg of oxycodone hydrochloride equivalent to 4.5 mg oxycodone and 2.5 mg naloxone hydrochloride twice a day and duloxetine 30 mg once a day. Following 3 months of this therapy, the patients could opt for MCT and were treated for a minimum of 6 months. Patient reported outcomes (PRO's) included: FIQR, VAS, ODI and SF-12 and lumbar range of motion (ROM) was recorded using the modified Schober test.While SAT led to minor improvement as compared with baseline status, the addition of MCT allowed a significantly higher improvement in all PRO's at 3 months after initiation of MCT and the improvement was maintained at 6 months. ROM improved after 3 months of MCT and continued to improve at 6 months.This observational cross-over study demonstrates an advantage of MCT in FM patients with LBP as compared with SAT. Further randomised clinical trial studies should assess whether these results can be generalised to the FM population at large.

Accumulating evidence suggests that brain white matter (WM) abnormalities may be central to the pathophysiology of psychotic disorders. In addition, there is evidence that cannabis use and alcohol use each is associated with WM abnormalities. However, there are very limited data on the effects of these substances on WM microstructure in patients with psychosis, especially for those at the early phase of illness. This project aimed to examine the impact of cannabis use and alcohol use on WM tissue in early-phase psychosis (EPP). WM was investigated in 21 patients with EPP using diffusion tensor imaging (DTI) and transverse relaxation time of tissue water (T2), with the primary outcomes being mean fractional anisotropy (FA) and T2. DTI analyses were performed at the full-brain level using tract-based spatial statistics with both DTI and T2 analysis done within a WM volume of interest (VOI) implicated in psychosis (containing the left superior longitudinal fasciculus). Our findings revealed that younger age of onset of regular alcohol use (more than one drink per week) was associated with lower FA values in the left thalamic radiation and left parahippocampal and left amygdalar WM. More frequent lifetime cannabis use was correlated with increased mean full-brain FA. There was no significant relationship found between FA and alcohol or cannabis use within the VOI. Relaxometry analysis revealed trend-level evidence of shortened T2 with later onset of regular alcohol use and with more frequent cannabis use. This study provides novel data demonstrating cortical and subcortical WM findings related to alcohol use in EPP and is the first to combine DTI and relaxometry, relating to this patient population.

The history of Cannabis goes along that of humankind, as speculated based on geographical and evolutionary models together with historic data collected to date. Its medical use is several thousand years old, as attested both by archeobotanical evidence of Cannabis remains and written records found in ancient texts from the sacred Vedic foundational texts of Ayurvedic medicine (about 800 before current era [BCE]) to the first known Pharmacopoea, the Chinese "Shen Nung Pen Ts'ao Ching" (1 century BCE). In this paper, we retrace the history of Cannabis traveling through the key stages of its diffusion among the most important ancient cultures up to our days, when we are facing a renaissance of its medical employment. We report through the centuries evidence of its use in numerous pathologic conditions especially for its anti-inflammatory, antiseptic, and anticonvulsing properties that support the requirement to direct our present research efforts into the definitive understanding of its efficacy.

Objective: We estimated whether recent cannabis use moderates response to cigarettes varying in nicotine content (0.4, 2.4, 5.2, 15.8 mg/g) among smokers with concurrent affective disorders, opioid dependence, or socioeconomic disadvantage. Methods: We conducted a secondary analysis of a multi-site, double-blind, laboratory study examining acute response to reduced nicotine content cigarettes (RNCC) in 169 adult smokers with co-morbid conditions. Participants positive for recent cannabis use or self-reported past 30-day cannabis use at baseline were categorized as current cannabis users (N = 63). Repeated measures analysis of variance tests assessed whether baseline cannabis use moderated cigarette reinforcement, tobacco withdrawal, craving, smoking topography, or carbon monoxide boost. Results: Cannabis users were younger, less educated, and had more depression and anxiety than non-users (p < .05). Cannabis use status did not moderate the effects of nicotine dose on concurrent choice testing, subjective effects of RNCCs, or smoking topography. After adjusting for sociodemographic characteristics, cannabis users had higher ratings on Smoking Satisfaction, Enjoyment of Respiratory Tract Sensations, and Craving Reduction across all nicotine doses. Cannabis users reported longer withdrawal symptom duration and more rapid decline of carbon monoxide boost than non-users. Conclusions: Findings suggest RNCCs decrease the addiction potential of cigarettes in vulnerable populations independent of cannabis use status.

Cannabis is the most commonly used illicit drug worldwide. Although its use is associated with multiple adverse health effects, including the risk of developing addiction, recreational and medical cannabis use is being increasing legalized. In addition, use of synthetic cannabinoid drugs is gaining considerable popularity and is associated with mass poisonings and occasional deaths. Delineating factors involved in cannabis use and addiction therefore becomes increasingly important. Similarly to other drugs of abuse, the prevalence of cannabis use and addiction differs remarkably between males and females, suggesting that sex plays a role in regulating cannabinoid sensitivity. Although it remains unclear how sex may affect the initiation and maintenance of cannabis use in humans, animal studies strongly suggest that endogenous sex hormones modulate cannabinoid sensitivity. In addition, synthetic anabolic-androgenic steroids alter substance use and further support the importance of sex steroids in controlling drug sensitivity. The recent discovery that pregnenolone, the precursor of all steroid hormones, controls cannabinoid receptor activation corroborates the link between steroid hormones and the endocannabinoid system. This article reviews the literature regarding the influence of endogenous and synthetic steroid hormones on the endocannabinoid system and cannabinoid action.

There is increasing scientific data suggesting that cannabis is beneficial for a large range of medical conditions. Physicians need up-to-date medical knowledge (i.e., indications, dose and safety properties) before prescribing cannabis for older patients, who are, a priori, more prone to its adverse effects than younger patients. A mini-review was conducted to examine the evidence on medical cannabis use in older patients.An English and French systematic Medline (PubMed) search, from January 1, 2001 to October 15, 2018, was conducted using the MeSH terms "Cannabis"[Mesh] OR "Marijuana Abuse"[Mesh] OR "Medical Marijuana"[Mesh] OR "Marijuana Smoking"[Mesh] combined with the MeSH terms ("Aged"[Mesh]) OR "Aged, 80 and over"[Mesh]. A total of 451 abstracts were identified and full relevant articles were retrieved and analysed.Even with a growing body of data showing positive effects of medical cannabis use, mixed results have been reported. Most clinical studies have had small samples and there are few randomized controlled trials. This lack of evidence on the positive clinical effects of medical cannabis use is especially marked for older patients, few of whom have been examined.There is a lack of consistent data on the clinical effects of medical cannabis use in older patients to guide cannabis prescription for this group of patients.

Use of illicit drugs by adolescents might facilitate or trigger other risky behaviors, including early sexual initiation (ESI), multiple partners, and unprotected sex. This study examines whether the age at which adolescents initiate cannabis use is associated with the age of their first sexual intercourse in the U.S. in 2015.A secondary analysis of data from the 2015 Youth Risk Behavior Surveillance Survey, a cross-sectional, nationally representative survey, was conducted (n = 7,664). Exposure of interest was age of initiation of cannabis use (never used cannabis, age 12 or younger, 13-14 years of age, and age 15 or older) and outcome was ESI (14 years old or younger). Unadjusted and adjusted odds ratios (OR) and their 95% confidence intervals were computed.Prevalence of ESI was 15.3%. The proportion of cannabis use was 39.9%. Adolescents starting cannabis use before the age of 15 had higher adjusted odds of ESI (OR ranged 4.2-6.7). This association is modified by sex: while in boys using cannabis before 13 years, the OR is 9 (95% CI 5.2-15.6); in girls, it is 2.8 (95% CI 1.7-4.7).Our findings suggest that there should be sex and drug education programs instituted before the age of 12 ideally, and no later than by age 15 since this time represents a critical period of initiating both behaviors.

Injection opioid use is associated with more severe health and psychosocial consequences relative to non-injection use, but few studies have examined whether injection use is associated with methadone maintenance treatment outcomes. The present study examined differential MMT outcomes among opioid injectors and non-injectors.Data were extracted from the clinic charts of opioid-dependent MMT patients (N = 290; n = 115 injectors) enrolled in a university-affiliated, urban MMT clinic. Injection status was examined as a predictor of short- (3-month opioid, cocaine, benzodiazepine and cannabis urine drug screens) and long- (days retained in treatment) term MMT outcomes.Bivariate analyses revealed injection users were less likely to be African American and to have completed high school, were more likely to have started heroin use before age 21, to report having hepatitis C, to report a baseline cocaine use disorder, and had higher methadone doses at 3-months into treatment. Injection status significantly predicted a greater proportion of cocaine-positive urine drug screens in the first 3 months of treatment, but did not significantly predict opioid, benzodiazepine or cannabis drug screens, or length of treatment retention.This is one of a handful of studies to examine injection status as a predictor of MMT outcomes. Injection status is associated with cocaine use early in treatment, which has implications for the focus of treatment.

Cannabis is the most widely used illicit substance in the world. An increasing number of jurisdictions have legalized medical and non-medical cannabis; comparisons across jurisdictions can help evaluate the impact of these policy innovations. The current study examined patterns of cannabis use among youth in Canada (CA), England (EN) and the United States (US). At the time of study, non-medical cannabis use was prohibited federally in all three countries; however, medical cannabis was accessible with varying restrictions in CA, EN and most US states, while non-medical cannabis was legal in four US states.Data come from an international online survey conducted in July 2017 (n = 12,064). Youth, aged 16-19, were asked about cannabis consumption, perceived access to cannabis, perceptions of harm, and driving after cannabis use. All estimates represent weighted data.US youth were more likely to report more frequent cannabis consumption, easier access, lower perceptions of harm, and higher rates of driving after cannabis use than CA and EN youth. CA youth reported more frequent consumption, easier access, and higher rates of driving after cannabis use than EN youth.CA and US youth had higher prevalence of use, easier access, lower perceived harm and higher driving rates after cannabis use in comparison to EN. These differences may reflect more permissive cannabis policies in CA and US, as well as pre-existing trends. Future waves of the international cannabis study will examine trends over time within the same countries after cannabis legalization in CA and additional US states.

Monitoring of blood levels of Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) is necessary for optimization of administration of medical cannabis. We describe the validation of a ultra-HPLC-MS/MS method for quantifying THC and CBD from plasma and decoctions and its application for therapeutic drug monitoring.Materials & methods: Analyses were performed by using a TSQ Quantiva™ Triple Quadrupole coupled to a Ultimate 3000 UHPLC system with atmospheric pressure chemical ionization after sample preparation with a straightforward method with deuterated internal standards.The method has been validated following EMA guidelines and is linear in plasma from 0.16 to 10 ng/ml for both THC and CBD and in decoctions from 4.7 to 600 ng/ml.Given the unpredictable pharmacokinetic behavior of THC and CBD in patients, monitoring of plasma concentrations is strongly recommended for patients under treatment with medical cannabis.

Objective This study determines the trend of acute myocardial infarction (AMI) in cannabis users. Demographic characteristics, hospitalization outcomes, and utilization of primary treatment modalities were evaluated in AMI inpatient population. Methods The study used data from the nationwide inpatient sample (NIS) for the years 2010-2014. We identified patients with AMI as the primary diagnosis (N = 379,843) and patients with cannabis use disorder as the secondary diagnosis. We used Pearson's chi-square (χ2) test and independent sample t-test for measuring the categorical and continuous data, respectively. Results Inpatient admissions for AMI among cannabis users increased by 32% (P = 0.001). The overall mean age of cannabis users with AMI (41 years) remained stable with no significant differences observed across age groups. AMI was predominant in male cannabis users (79.1%), and there was a 38.3% increase in the prevalence in female cannabis users over five years (P < 0.001). About one-third of the cannabis users with AMI were covered by medicaid with a 70.5% pike (21% in 2010 to 37.5% in 2014; P < 0.001). There was a strong linear trend in nonelective admissions for AMI in cannabis users (P = 0.003) along with a moderate-to-severe morbidity (P = 0.001). Mean length of inpatient stay had a decreasing linear trend (P = 0.003), whereas hospitalization costs were increasing (P = 0.024), averaging $65,879 per admission for AMI. Cannabis users had a strong linear increasing trend (P = 0.007), with a 60% increase in in-hospital mortality (1.0% in 2010 to 1.6% in 2014). Conclusion Due to the risk of AMI, as seen in numerous case reports, the trend of emergency admission and severe morbidity due to AMI in cannabis users is also increasing. Also, cannabis users have a higher healthcare cost to manage AMI, yet the in-hospital mortality has risen tremendously over the last few years. It is imperative to know that chronic cannabis worsens the outcomes in AMI patients, and more clinical studies are needed to show the association of episodic use in cannabis abusers and AMI.

Cannabis sativa is widely cultivated for medicinal, food, industrial, and recreational use, but much remains unknown regarding its genetics, including the molecular determinants of cannabinoid content. Here, we describe a combined physical and genetic map derived from a cross between the drug-type strain Purple Kush and the hemp variety "Finola." The map reveals that cannabinoid biosynthesis genes are generally unlinked but that aromatic prenyltransferase (AP), which produces the substrate for THCA and CBDA synthases (THCAS and CBDAS), is tightly linked to a known marker for total cannabinoid content. We further identify the gene encoding CBCA synthase (CBCAS) and characterize its catalytic activity, providing insight into how cannabinoid diversity arises in cannabis. THCAS and CBDAS (which determine the drug vs. hemp chemotype) are contained within large (>250 kb) retrotransposon-rich regions that are highly nonhomologous between drug- and hemp-type alleles and are furthermore embedded within ∼40 Mb of minimally recombining repetitive DNA. The chromosome structures are similar to those in grains such as wheat, with recombination focused in gene-rich, repeat-depleted regions near chromosome ends. The physical and genetic map should facilitate further dissection of genetic and molecular mechanisms in this commercially and medically important plant.

Robust evidence implicates perceived distress tolerance as a risk factor for maladaptive cannabis use and poorer cannabis cessation outcomes. Past work suggests that perceived distress tolerance may be related to an array of clinically-relevant cannabis processes and outcomes via cannabis coping motives. Although promising, the generalizability of this work to racially/ethnically diverse samples of adult cannabis users is unknown. Additionally, investigation into alternative cannabis processes has been limited and has not controlled for the effects of other cannabis motives. Thus, the present study investigated cannabis coping motives as an explanatory variable for the relation between perceived distress tolerance and cannabis use processes that may impede cessation (e.g., cannabis use cravings, perceived barriers to cannabis cessation, and withdrawal symptoms) among an ethnically diverse sample of current cannabis using adults. Participants included 131 adult cannabis users (Mage = 36.67 years; 29.8% female; 59.2% Black, 26.2% White, 16.0% Hispanic). Results indicated that perceived distress tolerance was indirectly associated with all criterion variables through cannabis coping motives after controlling for the variance attributable to four other motives. The current study builds upon previous theoretically-supported work by examining these models among an ethnically diverse sample of current cannabis using adults and testing alternative cessation-related cannabis processes while controlling for the independent effects of four other cannabis motives.

Associations between adolescent cannabis use and poor neurocognitive functioning have been reported from cross-sectional studies that cannot determine causality. Prospective designs can assess whether extended cannabis abstinence has a beneficial effect on cognition.Eighty-eight adolescents and young adults (aged 16-25 years) who used cannabis regularly were recruited from the community and a local high school between July 2015 and December 2016. Participants were randomly assigned to 4 weeks of cannabis abstinence, verified by decreasing 11-nor-9-carboxy-∆⁹-tetrahydrocannabinol urine concentration (MJ-Abst; n = 62), or a monitoring control condition with no abstinence requirement (MJ-Mon; n = 26). Attention and memory were assessed at baseline and weekly for 4 weeks with the Cambridge Neuropsychological Test Automated Battery.Among MJ-Abst participants, 55 (88.7%) met a priori criteria for biochemically confirmed 30-day continuous abstinence. There was an effect of abstinence on verbal memory (P = .002) that was consistent across 4 weeks of abstinence, with no time-by-abstinence interaction, and was driven by improved verbal learning in the first week of abstinence. MJ-Abst participants had better memory overall and at weeks 1, 2, 3 than MJ-Mon participants, and only MJ-Abst participants improved in memory from baseline to week 1. There was no effect of abstinence on attention: both groups improved similarly, consistent with a practice effect.This study suggests that cannabis abstinence is associated with improvements in verbal learning that appear to occur largely in the first week following last use. Future studies are needed to determine whether the improvement in cognition with abstinence is associated with improvement in academic and other functional outcomes.ClinicalTrials.gov identifier: NCT03276221.

Crohn's disease (CD) is a chronic immune-mediated condition of transmural inflammation in the gastrointestinal tract, associated with significant morbidity and decreased quality of life. The endocannabinoid system provides a potential therapeutic target for cannabis and cannabinoids and animal models have shown benefit in decreasing inflammation. However, there is also evidence to suggest transient adverse events such as weakness, dizziness and diarrhea, and an increased risk of surgery in people with CD who use cannabis.The objectives were to assess the efficacy and safety of cannabis and cannabinoids for induction and maintenance of remission in people with CD.We searched MEDLINE, Embase, AMED, PsychINFO, the Cochrane IBD Group Specialized Register, CENTRAL, ClinicalTrials.Gov, and the European Clinical Trials Register up to 17 October 2018. We searched conference abstracts, references and we also contacted researchers in this field for upcoming publications.Randomized controlled trials comparing any form of cannabis or its cannabinoid derivatives (natural or synthetic) to placebo or an active therapy for adults with Crohn's disease were included.Two authors independently screened search results, extracted data and assessed bias using the Cochrane risk of bias tool. The primary outcomes were clinical remission and relapse. Remission is commonly defined as a Crohn's disease activity index (CDAI) of < 150. Relapse is defined as a CDAI > 150. Secondary outcomes included clinical response, endoscopic remission, endoscopic improvement, histological improvement, quality of life, C-reactive protein (CRP) and fecal calprotectin measurements, adverse events (AEs), serious AEs, withdrawal due to AEs, and cannabis dependence and withdrawal effects. We calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI) for dichotomous outcomes. For continuous outcomes, we calculated the mean difference (MD) and 95% CI. Data were combined for analysis when the interventions, patient groups and outcomes were sufficiently similar (determined by consensus). Data were analyzed on an intention-to-treat basis and the overall certainty of the evidence supporting the outcomes was evaluated using the GRADE criteria.Three studies (93 participants) that assessed cannabis in people with active CD met the inclusion criteria. One ongoing study was also identified. Participants in two of the studies were adults with active Crohn's disease who had failed at least one medical treatment. The inclusion criteria for the third study were unclear. No studies that assessed cannabis therapy in quiescent CD were identified. The studies were not pooled due to differences in the interventional drug.One small study (N = 21) compared eight weeks of treatment with cannabis cigarettes containing 115 mg of D9-tetrahydrocannabinol (THC) to placebo cigarettes containing cannabis with the THC removed in participants with active CD. This study was rated as high risk of bias for blinding and other bias (cannabis participants were older than placebo). The effects of cannabis on clinical remission were unclear. Forty-five per cent (5/11) of the cannabis group achieved clinical remission compared with 10% (1/10) of the placebo group (RR 4.55, 95% CI 0.63 to 32.56; very low certainty evidence). A difference was observed in clinical response (decrease in CDAI score of >100 points) rates. Ninety-one per cent (10/11) of the cannabis group achieved a clinical response compared to 40% (4/10) of the placebo group (RR 2.27, 95% CI 1.04 to 4.97; very low certainty evidence). More AEs were observed in the cannabis cigarette group compared to placebo (RR 4.09, 95% CI 1.15 to 14.57; very low certainty evidence). These AEs were considered to be mild in nature and included sleepiness, nausea, difficulty with concentration, memory loss, confusion and dizziness. This study did not report on serious AEs or withdrawal due to AEs.One small study (N = 22) compared cannabis oil (5% cannabidiol) to placebo oil in people with active CD. This study was rated as high risk of bias for other bias (cannabis participants were more likely than placebo participants to be smokers). There was no difference in clinical remission rates. Forty per cent (4/10) of cannabis oil participants achieved remission at 8 weeks compared to 33% (3/9) of the placebo participants (RR 1.20, 95% CI 0.36 to 3.97; very low certainty evidence). There was no difference in the proportion of participants who had a serious adverse event. Ten per cent (1/10) of participants in the cannabis oil group had a serious adverse event compared to 11% (1/9) of placebo participants (RR 0.90, 95% CI 0.07 to 12.38, very low certainty evidence). Both serious AEs were worsening Crohn's disease that required rescue intervention. This study did not report on clinical response, CRP, quality of life or withdrawal due to AEs.One small study (N= 50) compared cannabis oil (15% cannabidiol and 4% THC) to placebo in participants with active CD. This study was rated as low risk of bias. Differences in CDAI and quality of life scores measured by the SF-36 instrument were observed. The mean quality of life score after 8 weeks of treatment was 96.3 in the cannabis oil group compared to 79.9 in the placebo group (MD 16.40, 95% CI 5.72 to 27.08, low certainty evidence). After 8 weeks of treatment, the mean CDAI score was118.6 in the cannabis oil group compared to 212.6 in the placebo group (MD -94.00, 95%CI -148.86 to -39.14, low certainty evidence). This study did not report on clinical remission, clinical response, CRP or AEs.The effects of cannabis and cannabis oil on Crohn's disease are uncertain. Thus no firm conclusions regarding the efficacy and safety of cannabis and cannabis oil in adults with active Crohn's disease can be drawn. The effects of cannabis or cannabis oil in quiescent Crohn's disease have not been investigated. Further studies with larger numbers of participants are required to assess the potential benefits and harms of cannabis in Crohn's disease. Future studies should assess the effects of cannabis in people with active and quiescent Crohn's disease. Different doses of cannabis and delivery modalities should be investigated.

Cannabis use is prevalent but only a minority of regular users develop cannabis use disorder (CUD); thus, CUD risk identification among current cannabis users is vital for targeted intervention development. Existing data suggest that high distress intolerance (DI), an individual difference reflective of the ability to withstand negative affect, is linked to CUD, possibly via stress-elicited impairment of response inhibition but this has never been explicitly tested. Frequent cannabis users with high and low DI completed a go/no-go task during EEG recording before and after a laboratory stressor. Relations between DI, cannabis use-related problems, and behavioral as well as neurophysiological markers of response inhibition functioning were assessed. DI significantly moderated the effect of the stressor on the conflict-monitoring but not evaluative phase of response inhibition as measured by N2 and P3a amplitude, respectively. Unexpectedly, cannabis users with high DI demonstrated stressor-elicited enhancement rather than impairment of conflict-monitoring neural activity, which was related to faster reaction time (RT) and decreased past-month cannabis problems. Enhanced inhibition-related modulation of P3a amplitude was generally associated with increased cannabis problems regardless of acute stress. Results did not provide support for stress-elicited impairment in cognitive control as a mechanism linking high DI and CUD, though some support was found for the relevance of inhibition-related neural activity to CUD. Stress-elicited enhancement of conflict-monitoring neural activity during response inhibition may reflect an adaptive neural response among cannabis users with high DI that protects against CUD in this at-risk group. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Promising treatment avenues have been developed and studied that align well with the skills of psychiatric-mental health (PMH) nurses. The treatments are relationship-driven, nimble and accessible, and recovery-guided. They emphasize a whole-person approach with care delivered by a team of experts working in a contextually coordinated way.To describe the challenges facing the United States with regard to mental illness and substance use disorders and the ways in which PMH nurses can use their skills to mitigate these challenges.Published research and government reports were reviewed to obtain current mental health and substance use data.The number of people not being treated for mental illnesses-particularly serious mental illness, major depressive episode, and suicidal thoughts-has not improved since 2009. Although inroads have been made in reducing the rate of smoking in the United States, we are facing an opioid crisis. There are limited data on marijuana use, but it is apparent that many Americans use cannabis routinely. According to the Substance Abuse and Mental Health Administration, approximately 44.7 million people need mental health treatment and 20.1 million Americans need substance use treatment, but only 10% to 30% receive it.PMH nurses must take a leading role in retooling the therapeutic relationship and partnering with clients, families, and caregivers to improve the quality of life and well-being of those dealing with mental illness and substance use disorders. To accomplish this essential task, the PMH nursing workforce must be robust and distributed throughout the United States.

Cannabis and cannabinoids are often promoted as treatment for many illnesses and are widely used among patients with ulcerative colitis (UC). Few studies have evaluated the use of these agents in UC. Further, cannabis has potential for adverse events and the long-term consequences of cannabis and cannabinoid use in UC are unknown.To assess the efficacy and safety of cannabis and cannabinoids for the treatment of patients with UC.We searched MEDLINE, Embase, WHO ICTRP, AMED, PsychINFO, the Cochrane IBD Group Specialized Register, CENTRAL, ClinicalTrials.Gov and the European Clinical Trials Register from inception to 2 January 2018. Conference abstracts and references were searched to identify additional studies.Randomized controlled trials (RCTs) comparing any form or dose of cannabis or its cannabinoid derivatives (natural or synthetic) to placebo or an active therapy for adults (> 18 years) with UC were included.Two authors independently screened search results, extracted data and assessed bias using the Cochrane risk of bias tool. The primary outcomes were clinical remission and relapse (as defined by the primary studies). Secondary outcomes included clinical response, endoscopic remission, endoscopic response, histological response, quality of life, C-reactive protein (CRP) and fecal calprotectin measurements, symptom improvement, adverse events, serious adverse events, withdrawal due to adverse events, psychotropic adverse events, and cannabis dependence and withdrawal effects. We calculated the risk ratio (RR) and corresponding 95% confidence interval for dichotomous outcomes. For continuous outcomes, we calculated the mean difference (MD) and corresponding 95% CI. Data were pooled for analysis when the interventions, patient groups and outcomes were sufficiently similar (determined by consensus). Data were analyzed on an intention-to-treat basis. GRADE was used to evaluate the overall certainty of evidence.Two RCTs (92 participants) met the inclusion criteria. One study (N = 60) compared 10 weeks of cannabidiol capsules with up to 4.7% D9-tetrahydrocannabinol (THC) with placebo capsules in participants with mild to moderate UC. The starting dose of cannabidiol was 50 mg twice daily increasing to 250 mg twice daily if tolerated. Another study (N = 32) compared 8 weeks of therapy with two cannabis cigarettes per day containing 0.5 g of cannabis, corresponding to 23 mg THC/day to placebo cigarettes in participants with UC who did not respond to conventional medical treatment. No studies were identified that assessed cannabis therapy in quiescent UC. The first study was rated as low risk of bias and the second study (published as an abstract) was rated as high risk of bias for blinding of participants and personnel. The studies were not pooled due to differences in the interventional drug.The effect of cannabidiol capsules (100 mg to 500 mg daily) compared to placebo on clinical remission and response is uncertain. Clinical remission at 10 weeks was achieved by 24% (7/29) of the cannabidiol group compared to 26% (8/31) in the placebo group (RR 0.94, 95% CI 0.39 to 2.25; low certainty evidence). Clinical response at 10 weeks was achieved in 31% (9/29) of cannabidiol participants compared to 22% (7/31) of placebo patients (RR 1.37, 95% CI 0.59 to 3.21; low certainty evidence). Serum CRP levels were similar in both groups after 10 weeks of therapy. The mean CRP in the cannabidiol group was 9.428 mg/L compared to 7.638 mg/L in the placebo group (MD 1.79, 95% CI -5.67 to 9.25; moderate certainty evidence). There may be a clinically meaningful improvement in quality of life at 10 weeks, measured with the IBDQ scale (MD 17.4, 95% CI -3.45 to 38.25; moderate certainty evidence). Adverse events were more frequent in cannabidiol participants compared to placebo. One hundred per cent (29/29) of cannabidiol participants had an adverse event, compared to 77% (24/31) of placebo participants (RR 1.28, 95% CI 1.05 to1.56; moderate certainty evidence). However, these adverse events were considered to be mild or moderate in severity. Common adverse events included dizziness, disturbance in attention, headache, nausea and fatigue. None (0/29) of the cannabidiol participants had a serious adverse event compared to 13% (4/31) of placebo participants (RR 0.12, 95% CI 0.01 to 2.11; low certainty evidence). Serious adverse events in the placebo group included worsening of UC and one complicated pregnancy. These serious adverse events were thought to be unrelated to the study drug. More participants in the cannabidiol group withdrew due to an adverse event than placebo participants. Thirty-four per cent (10/29) of cannabidiol participants withdrew due to an adverse event compared to 16% (5/31) of placebo participants (RR 2.14, 95% CI 0.83 to 5.51; low certainty evidence). Withdrawls in the cannabidiol group were mostly due to dizziness. Withdrawals in the placebo group were due to worsening UC.The effect of cannabis cigarettes (23 mg THC/day) compared to placebo on mean disease activity, CRP levels and mean fecal calprotectin levels is uncertain. After 8 weeks, the mean disease activity index score in cannabis participants was 4 compared with 8 in placebo participants (MD -4.00, 95% CI -5.98 to -2.02). After 8 weeks, the mean change in CRP levels was similar in both groups (MD -0.30, 95% CI -1.35 to 0.75; low certainty evidence). The mean fecal calprotectin level in cannabis participants was 115 mg/dl compared to 229 mg/dl in placebo participants (MD -114.00, 95% CI -246.01 to 18.01). No serious adverse events were observed. This study did not report on clinical remission, clinical response, quality of life, adverse events or withdrawal due to adverse events.The effects of cannabis and cannabidiol on UC are uncertain, thus no firm conclusions regarding the efficacy and safety of cannabis or cannabidiol in adults with active UC can be drawn.There is no evidence for cannabis or cannabinoid use for maintenance of remission in UC. Further studies with a larger number of patients are required to assess the effects of cannabis in UC patients with active and quiescent disease. Different doses of cannabis and routes of administration should be investigated. Lastly, follow-up is needed to assess the long term safety outcomes of frequent cannabis use.

Cannabis is a chemically diverse domesticated plant genus which produces a unique class of biologically active secondary metabolites referred to as cannabinoids. The affinity and selectivity of cannabinoids to targets of the human endocannabinoid system depend on alkyl side chain length, and these structural-activity relationships can be utilized for the development of novel therapeutics. Accurate early screening of germplasm has the potential to accelerate selection of chemical phenotypes (chemotypes) for pharmacological exploitation. However, limited attempts have been made to characterize the plasticity of alkyl cannabinoid composition in different plant tissues and throughout development. A chemotypic diversity panel comprised of 99 individuals from 20 Cannabis populations sourced from the Ecofibre Global Germplasm Collection (ecofibre.com.au and anandahemp.com) was used to examine alkyl cannabinoid variation across vegetative, flowering and maturation stages. A wide range of di-/tri-cyclic as well as C3-/C5-alkyl cannabinoid composition was observed between plants. Chemotype at the vegetative and flowering stages was found to be predictive of chemotype at maturation, indicating a low level of plasticity in cannabinoid composition. Chemometric cluster analysis based on composition data from all three developmental stages categorized alkyl cannabinoid chemotypes into three classes. Our results suggest that more extensive chemical and genetic characterization of the Cannabis genepool could facilitate the metabolic engineering of alkyl cannabinoid chemotypes.

Neurological therapeutics have been hampered by its inability to advance beyond symptomatic treatment of neurodegenerative disorders into the realm of actual palliation, arrest or reversal of the attendant pathological processes. While cannabis-based medicines have demonstrated safety, efficacy and consistency sufficient for regulatory approval in spasticity in multiple sclerosis (MS), and in Dravet and Lennox-Gastaut Syndromes (LGS), many therapeutic challenges remain. This review will examine the intriguing promise that recent discoveries regarding cannabis-based medicines offer to neurological therapeutics by incorporating the neutral phytocannabinoids tetrahydrocannabinol (THC), cannabidiol (CBD), their acidic precursors, tetrahydrocannabinolic acid (THCA) and cannabidiolic acid (CBDA), and cannabis terpenoids in the putative treatment of five syndromes, currently labeled recalcitrant to therapeutic success, and wherein improved pharmacological intervention is required: intractable epilepsy, brain tumors, Parkinson disease (PD), Alzheimer disease (AD) and traumatic brain injury (TBI)/chronic traumatic encephalopathy (CTE). Current basic science and clinical investigations support the safety and efficacy of such interventions in treatment of these currently intractable conditions, that in some cases share pathological processes, and the plausibility of interventions that harness endocannabinoid mechanisms, whether mediated via direct activity on CB1 and CB2 (tetrahydrocannabinol, THC, caryophyllene), peroxisome proliferator-activated receptor-gamma (PPARγ; THCA), 5-HT1A (CBD, CBDA) or even nutritional approaches utilizing prebiotics and probiotics. The inherent polypharmaceutical properties of cannabis botanicals offer distinct advantages over the current single-target pharmaceutical model and portend to revolutionize neurological treatment into a new reality of effective interventional and even preventative treatment.

Cannabis sativa is a medicinal herb with a diverse range of chemotypes that can exert both anxiolytic and anxiogenic effects on humans. Medical cannabis patients receiving organically grown cannabis from a single source were surveyed about the effectiveness of cannabis for treating anxiety. Patients rated cannabis as highly effective overall for treating anxiety with an average score of 8.03 on a Likert scale of 0 to 10 (0 = not effective, 10 = extremely effective). Patients also identified which strains they found the most or least effective for relieving their symptoms of anxiety. To find correlations between anxiolytic activity and chemotype, the top four strains voted most and least effective were analyzed by HPLC-MS/MS to quantify cannabinoids and GC-MS to quantify terpenes. Tetrahydrocannabinol (THC) and trans-nerolidol have statistically significant correlations with increased anxiolytic activity. Guiaol, eucalyptol, γ-terpinene, α-phellandrene, 3-carene, and sabinene hydrate all have significant correlations with decreased anxiolytic activity. Further studies are needed to better elucidate the entourage effects that contribute to the anxiolytic properties of cannabis varieties.

Background Recent trends in the legalization of marijuana in many states are increasing the popularity of recreational marijuana use. Since current data on hospitalizations in marijuana users is sparse, we evaluated the primary reasons for admissions, procedures and associated healthcare burden in hospitalized recreational marijuana users. Methods The National Inpatient Sample (NIS) for the years 2010-2014 was queried for the hospitalizations with a history of recreational marijuana usage using applicable ICD-9 CM codes. Descriptive statistics were used to report frequency (N) and percentage (%). Discharge weights were applied to achieve national estimates. The predictors of in-hospital mortality in recreational marijuana users were assessed using a two-way hierarchical multivariate regression after adjusting for the confounders. Results  We analyzed 465,959 (weighted n=2,317,343) hospitalizations with a history of recreational marijuana use. Among psychiatric disorders, most prominent primary discharge diagnoses were mood disorders (20.6%), schizophrenia/other psychotic disorders (10.6%), and substance/alcohol-related disorders (10.4%). Suicide and intentional self-inflicted injury (3.6%) was the leading cause of emergency admission. The most common non-psychiatric primary discharge diagnoses were diabetes mellitus with chronic complications (2.2%), acute myocardial infarction (AMI) (1.2%), nonspecific chest pain (1.1%), congestive cardiac failure (CHF) (1%), arrhythmia (0.8%), and hypertension (0.8%). Acute cerebrovascular diseases were noted in 1.1% and epilepsy in 1.8% of patients. Alcohol/drug rehabilitation and detoxification (6.9%) and psychiatric evaluation/therapy (3.9%) were the most evident psychiatric procedures whereas most frequent non-psychiatric procedures were diagnostic coronary arteriography (1%), percutaneous transluminal coronary angioplasty (0.7%), and echocardiogram (0.7%). Top independent predictors of in-hospital mortality were coagulopathy (OR 5.94), AMI (OR 4.59), pulmonary circulation disorder (OR 2.95), CHF (OR 2.02), renal failure (OR 1.91), coronary atherosclerosis (OR 1.34) and peripheral vascular disorder (OR 1.31). Major cardiovascular and cerebrovascular events also showed increasing trends among users. Conclusion We established the most frequent psychiatric and non-psychiatric causes of admissions and procedures in recreational marijuana users, which may pose a significant healthcare burden and increase the odds of in-hospital mortality.

To investigate how young and older people perceive the harms associated with legal and illegal drugs.Cross-sectional study: adults aged 18-24 years versus 45+ completed an online survey ranking the perceived harms associated with 11 drugs on 16 drug-related harm criteria.Online survey.184 participants aged 18-24 years (113 female: mean age 21: SD 1.3) and 91 participants aged 45+ (51 female: mean age 60: SD 8.5).'Perception of drug-related harms': This was measured using a rating scale ranging from 1 (no risk of harm) to 4 (high risk of harm). Participants were also asked about sources which informed their perception on drug-related harms as well as their own personal self-reported drug experiences.Of the illegal drugs, heroin, methamphetamine and cocaine were rated as the most harmful and cannabis was rated as the least harmful. Alcohol and tobacco were also rated as less harmful. The results showed that perceptions of drug-related harms were inconsistent with current knowledge from research on drugs. Furthermore, perceptions on drug harms were more conservative in the 45+ group for a number of illegal drugs and tobacco. However, the 45+ age group did not perceive alcohol as any more harmful than the younger group.This survey demonstrates that the greatest misperception was in relation to alcohol-related harms which did not change with age. In order to minimise harms, this misperception needs to be addressed through education and policies that legislate drug use.

Mental health and substance use disorders are the leading causes of global disability in children and youth. Both tend to first onset or escalate in adolescence and young adulthood, calling for effective prevention during this time. The Climate Schools Combined (CSC) study was the first trial of a Web-based combined universal approach, delivered through school classes, to prevent both mental health and substance use problems in adolescence. There is also limited evidence for the cost-effectiveness of school-based prevention programs.The aim of this protocol paper is to describe the CSC follow-up study, which aims to determine the long-term efficacy and cost-effectiveness of the CSC prevention program for depression, anxiety, and substance use (alcohol and cannabis use) up to 7 years post intervention.A cluster randomized controlled trial (the CSC study) was conducted with 6411 participants aged approximately 13.5 years at baseline from 2014 to 2016. Participating schools were randomized to 1 of 4 conditions: (1) control (health education as usual), (2) Climate Substance Use (universal substance use prevention), (3) Climate Mental Health (universal mental health prevention), or (4) CSC (universal substance use and mental health prevention). It was hypothesized that the CSC program would be more effective than conditions (1) to (3) in reducing alcohol and cannabis use (and related harms), anxiety, and depression symptoms as well as increasing knowledge related to alcohol, cannabis, anxiety, and depression. This long-term study will invite follow-up participants to complete 3 additional Web-based assessments at approximately 5, 6, and 7 years post baseline using multiple sources of locator information already provided to the research team. The primary outcomes include alcohol and cannabis use (and related harms) and mental health symptoms. An economic evaluation of the program will also be conducted using both data linkage as well as self-report resource use and quality of life measures. Secondary outcomes include self-efficacy, social networks, peer substance use, emotion regulation, and perfectionism. Analyses will be conducted using multilevel mixed-effects models within an intention-to-treat framework.The CSC long-term follow-up study is funded from 2018 to 2022 by the Australian National Health and Medical Research Council (APP1143555). The first follow-up wave commences in August 2018, and the results are expected to be submitted for publication in 2022.This is the first study to provide a long-term evaluation of combined universal substance use and mental health prevention up to 7 years post intervention. Evidence of sustained benefits into early adulthood would provide a scalable, easy-to-implement prevention strategy with the potential for widespread dissemination to reduce the considerable harms, burden of disease, injury, and social costs associated with youth substance use and mental disorders.PRR1-10.2196/11372.

Substance use disorders are associated with poorer clinical outcomes in patients with schizophrenia. There is no specific treatment for amphetamine or cannabis use disorder, but methadone and buprenorphine are used as replacement therapy in the treatment of opioid dependence. Our aim was to study whether patients with schizophrenia have received opioid replacement therapy for their opioid use disorder.The study sample consisted of 148 individuals diagnosed with schizophrenia who were in involuntary psychiatric treatment as forensic patients in Finland in 2012. The proportion of the study sample with comorbid opioid use disorder having received opioid replacement therapy prior to their forensic psychiatric treatment was compared to the available information of opioid dependent patients in general. The data were collected from forensic examination statements, patient files and other medical registers retrospectively.Of the study sample, 15.6% (23/148) had a history of opioid use disorder, of whom 8.7% (2/23) had received opioid replacement treatment (95% confidence interval (Cl): 1.1-28.0), even though opioid use disorder had been diagnosed in the treatment system. According the available information the corresponding proportion among patients with opioid use disorder and using substance use disorder services was 30.4% (565/1860, 95% Cl: 28.3-32.5). The fraction of patients receiving opioid replacement therapy was significantly lower among patients with schizophrenia (p = 0.022).Opioid replacement therapy was seldom used among schizophrenia patients who were later ordered to involuntary forensic psychiatric treatment. More attention should be paid to the possible use of opioids when planning treatment for patients with schizophrenia.Our study is not a randomized controlled trial (but a register-based study); thus the trial registration is not applicable.

Harmful effects of cannabis use in youth scale with frequency. In the context of approaching legalization in Canada, understanding the distinctions between youth who change and who maintain their cannabis use is essential for designing interventions and policy. A substantial number of characteristics may play a role. This study assessed whether and how youth who change their cannabis use differ from those who do not.Cannabis use was reported by 8375 Canadian high school students participating in the COMPASS study. GEE multiple logistic regressions were then used to establish impact of 13 baseline demographic and behavioural exposure variables on the likelihood of membership in four frequency change groups at follow-up a year later: reduction, cessation, escalation, and maintenance.Groups were found to differ in several ways. Cessation group members (19.4% of users) were less likely to binge drink (OR 0.82), vape (OR 0.82), or attend class without completing homework (OR 0.72) than maintainers. Students who reduced their use (14.6% of users) were more likely to binge drink (OR 1.36), smoke (OR 1.20), and skip class (OR 1.21). Those who escalated (29.5% of users) were more likely to be male (OR 1.35) and to vape (OR 1.22).Students who change their cannabis use differ in several demographic and behavioural characteristics. The results raise further concerns about the impact of e-cigarettes and the role of poly-substance use in high-risk trajectories. Distinct classes of cannabis users, essential for policy and intervention development, can be identified in high school populations.

Chronic hepatitis C virus (HCV) infection is one of the most common chronic liver diseases. Several risk factors for the progression of liver fibrosis among these patients have been identified. Use of cannabis could be another risk factor, but the results from epidemiological studies remain inconclusive.Comprehensive literature review was conducted using MEDLINE and EMBASE databases through December 2017 to identify studies that compared the risk of advanced liver fibrosis among HCV-infected patients who use and who do not use cannabis. Effect estimates from each study were extracted and combined together using the random-effect, generic inverse variance method of DerSimonian and Laird.A total of three cohort studies with 898 participants met the eligibility criteria and were included in the meta-analysis. The risk of advanced liver fibrosis among HCV-infected patients who use cannabis was numerically higher than those who do not use cannabis, although the result did not achieve statistical significance (pooled odds ratio, 1.77; 95% confidence interval, 0.78-4.02). The statistical heterogeneity was high with an I2 of 75%.This meta-analysis showed that the risk of advanced liver fibrosis among HCV-infected patients who use cannabis was higher than those who do not use cannabis, but the result was not statistically significant. Further studies are required to better characterize the risk.

Phytochemical studies on the liverwort Radula genus have previously identified the bibenzyl (-)-cis-perrottetinene (cis-PET), which structurally resembles (-)-Δ9-trans-tetrahydrocannabinol (Δ9-trans-THC) from Cannabis sativa L. Radula preparations are sold as cannabinoid-like legal high on the internet, even though pharmacological data are lacking. Herein, we describe a versatile total synthesis of (-)-cis-PET and its (-)-trans diastereoisomer and demonstrate that both molecules readily penetrate the brain and induce hypothermia, catalepsy, hypolocomotion, and analgesia in a CB1 receptor-dependent manner in mice. The natural product (-)-cis-PET was profiled on major brain receptors, showing a selective cannabinoid pharmacology. This study also uncovers pharmacological differences between Δ9-THC and PET diastereoisomers. Most notably, (-)-cis-PET and (-)-trans-PET significantly reduced basal brain prostaglandin levels associated with Δ9-trans-THC side effects in a CB1 receptor-dependent manner, thus mimicking the action of the endocannabinoid 2-arachidonoyl glycerol. Therefore, the natural product (-)-cis-PET is a psychoactive cannabinoid from bryophytes, illustrating the existence of convergent evolution of bioactive cannabinoids in the plant kingdom. Our findings may have implications for bioprospecting and drug discovery and provide a molecular rationale for the reported effects upon consumption of certain Radula preparations as moderately active legal highs.

Medical cannabis may be effective treatment for refractory epilepsy. It is timely to seek users' and potential users' opinions in regard to its place in the management of epilepsy.An online survey was administered to members of an epilepsy support organisation in Western Australia. Experience with cannabis for management of epilepsy was explored, along with desire to trial a particular pharmaceutical formulation(s).People with epilepsy (33/71) and carers (38/71) participated. Fifty-four participants indicated no experience with medical cannabis, although 35, mainly with inadequate response to prescription medicines, were willing to ask for a prescription. Concerns included difficulty accessing cannabis and high cost of this treatment. Tablets/capsules was the most acceptable dosage form for development.These findings suggest wide interest in trialling medical cannabis in individual cases of refractory epilepsy, despite the developing body of literature and some concerns about cost and procurement.

Radon is the second leading cause of lung cancer, after tobacco smoke. While tobacco smoke-induced carcinogenesis has been studied extensively, far less is known about radon-induced carcinogenesis, particularly in relation to the influence of radon on gene expression. The objectives of the work described herein were to (a) determine if and how exposure to low dose radon-emitting rock influences cells, at the gene expression level, and (b) compare any gene expression changes resulting from the exposure to radon-emitting rock with those induced by exposure to tobacco smoke. Any potential radiation-induced gene expression changes were also compared to those induced by exposure to cannabis smoke, a non-carcinogen at low doses, used here as a smoke exposure comparator. Human lung epithelial cells were exposed to radon-emitting rock, tobacco smoke or cannabis smoke, over months, and RNA-sequencing was carried out. We found that the rock-exposed cells experienced significant gene expression changes, particularly of the gene AKR1C3, and that these changes, over time, increasingly reflected those associated with exposure to tobacco, but not cannabis, smoke. We postulate that the early gene expression changes common to both the radiation and tobacco smoke exposures constitute a related - potentially pre-carcinogenic - response. Our findings suggest that the length of time a dividing population of cells is exposed to a constant low concentration of radon (with a potential cumulative absorbed dose) could be an important risk parameter for neoplastic transformation/carcinogenesis.

Whether the effects of cannabis use on brain function persist or recover following abstinence remains unclear. Therefore, using meta-analytic techniques, we examined whether functional alterations measured using fMRI persist in cannabis users abstinent for over 25 days (or 600 h) as evidence suggests that the effects on cognitive performance no longer persist beyond this period. Systematic literature search identified 20 studies, of which, 12 examined current cannabis users (CCU) (361 CCU versus 394 non-cannabis using controls (NU)) and 3 examined abstinent cannabis users (ACU) in 5 separate comparisons (98 ACU versus 106 NU). Studies in ACU were carried out in adolescents and suggest significantly greater activation in components of the central executive and default mode networks in adolescent ACU compared to NU. While this evidence is to be interpreted with caution because studies were carried out in overlapping samples, they indicate a pressing need for independent confirmation whether certain neurofunctional alterations in adolescent cannabis users may persist even after cannabis and its metabolites are likely to have left their bodies.

Characterizing patterns of adolescent cannabis use (CU), as well as risk factors and outcomes uniquely associated with these pathways is essential for informing treatment and prevention efforts. Yet, few studies have examined these issues among youth at-risk of engaging in problematic cannabis use. Further, research accounting for use of other substances or sex differences in patterns of CU remains exceedingly sparse.Trajectory-based modeling was used to identify underlying CU pathways among a predominantly Hispanic (90%) sample of at-risk youth (n = 401; 46% female) across adolescence (ages∼14-18), controlling for baseline substance use and participant demographics. Adolescent psychopathology (i.e., conduct disorder, attention deficit hyperactivity disorder, anxiety, and depression) was examined as a predictor and outcome of CU.Three trajectories of adolescent CU were identified, with most youth (74%) engaging in relatively "low" levels of use, followed by ∼12% exhibiting an early-initiating "chronic" course, and 14% "escalating" in use. Although boys and girls both experienced increased levels of CU across adolescence, boys were more likely to exhibit escalating and chronic patterns of use. Findings revealed unique associations between adolescent CU pathways and facets of psychopathology; most notably, the relatively robust and bidirectional association between CU trajectories and conduct problem symptoms.Specific facets of psychopathology may confer unique associations with CU across development, including the initiation and exacerbation of CU during adolescence.

Qualitative study.The objective of this study was to compare the perceptions of patients and surgeons regarding the risks and benefits of lumbar decompressive surgery for sciatica following a consultation meeting.Evidence regarding pain improvement in patients following lumbar decompressive surgery for sciatica is inconsistent. Given this inconsistency, patients choosing to undergo lumbar decompressive surgery must accept the risks associated with the surgery despite uncertainty regarding benefits. This raises questions as to the nature of informed decision-making for patients choosing to undergo surgery for sciatica.We undertook a qualitative descriptive study with 12 adult lumbar decompressive surgery candidates and 6 of their spine surgeons and analyzed data using inductive content analysis.Our analysis revealed that most patients were satisfied with the consultation despite limited understanding of lumbar decompressive surgery. We found discrepancies between patients' preoperative expectations and understanding of information provided by surgeons and what surgeons believed they had conveyed. Surgeons and patients disagreed on how much information is needed about post-surgical activity modifications and long-term outcomes in order to make a decision about whether or not to undergo surgery, with patients desiring more information. As a result, for most patients, the decision-making process extended beyond the information provided by surgeons and incorporated information from family members, friends, family doctors and the internet.Our results highlight misunderstandings between patients and surgeons, particularly in regard to prognosis and activity modifications. Since this information is important for patients choosing whether to undergo a surgical intervention, our study provides guidance to improve informed decisions about sciatica and, potentially, other elective surgeries.4.

Alcohol and drug use can have negative consequences on the health, economy, productivity, and social aspects of communities. We aimed to use data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 to calculate global and regional estimates of the prevalence of alcohol, amphetamine, cannabis, cocaine, and opioid dependence, and to estimate global disease burden attributable to alcohol and drug use between 1990 and 2016, and for 195 countries and territories within 21 regions, and within seven super-regions. We also aimed to examine the association between disease burden and Socio-demographic Index (SDI) quintiles.We searched PubMed, EMBASE, and PsycINFO databases for original epidemiological studies on alcohol and drug use published between Jan 1, 1980, and Sept 7, 2016, with out language restrictions, and used DisMod-MR 2.1, a Bayesian meta-regression tool, to estimate population-level prevalence of substance use disorders. We combined these estimates with disability weights to calculate years of life lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 1990-2016. We also used a comparative assessment approach to estimate burden attributable to alcohol and drug use as risk factors for other health outcomes.Globally, alcohol use disorders were the most prevalent of all substance use disorders, with 100·4 million estimated cases in 2016 (age-standardised prevalence 1320·8 cases per 100 000 people, 95% uncertainty interval [95% UI] 1181·2-1468·0). The most common drug use disorders were cannabis dependence (22·1 million cases; age-standardised prevalence 289·7 cases per 100 000 people, 95% UI 248·9-339·1) and opioid dependence (26·8 million cases; age-standardised prevalence 353·0 cases per 100 000 people, 309·9-405·9). Globally, in 2016, 99·2 million DALYs (95% UI 88·3-111·2) and 4·2% of all DALYs (3·7-4·6) were attributable to alcohol use, and 31·8 million DALYs (27·4-36·6) and 1·3% of all DALYs (1·2-1·5) were attributable to drug use as a risk factor. The burden of disease attributable to alcohol and drug use varied substantially across geographical locations, and much of this burden was due to the effect of substance use on other health outcomes. Contrasting patterns were observed for the association between total alcohol and drug-attributable burden and SDI: alcohol-attributable burden was highest in countries with a low SDI and middle-high middle SDI, whereas the burden due to drugs increased with higher S DI level.Alcohol and drug use are important contributors to global disease burden. Effective interventions should be scaled up to prevent and reduce substance use disease burden.Bill & Melinda Gates Foundation and Australian National Health and Medical Research Council.

France is the only European country with a dedicated addictovigilance network (French addictovigilance network [FAN]). However, the reporting of cases of abuse/dependence is insufficient. In an attempt to overcome this under-reporting, data from the medical information systems program (PMSI) is regularly used to identify cases. Since addictions are frequently associated with psychiatric comorbidities, a pilot study was conducted for the first time in a psychiatric hospital. It aims, through a PMSI request, to identify the sociodemographic characteristics and psychiatric diagnoses of patients consuming psychoactive substances (PAS) and the PAS types consumed.This is a retrospective observational study conducted over a nine-month period at the psychotherapeutic center of Nancy (CPN). The codes used for the PMSI request are those of the international classification of diseases, tenth revision (ICD-10), codes F10 to F19 that characterize mental and behavioral disorders associated with the use of PAS. Cases presenting the four criteria necessary for an addictovigilance notification: (1) identified notifier, (2) identified patient, (3) known consumed product (s) and (4) presence of an effect related to the abuse/dependence of PAS; were retained and analyzed.On an initial number of 252 cases, 82 cases of abuse/dependence were retained. The selected sample is predominantly male (67%). Cannabis (29%) and heroin (15%) are the most common illicit PAS. Regarding drugs, the consumption of benzodiazepines, a predominantly female phenomenon, is observed in 34% of subjects. Sixty-four per cent of the subjects were diagnosed "disorders related to the use of PAS", 14% as neurotic disorders, 9% as schizophrenia and 5% as of the mood disorders.This study identified a significant number of potentially reportable cases to the French Addictovigilance Network and demonstrated the interest of investigating cases of abuse/dependence in a psychiatric hospital.

Racial minorities are at greater risk of cardiovascular disease (CVD), and CVD is the primary cause of mortality among human immunodeficiency virus (HIV)-infected individuals. Cocaine use also has been associated with hypertension. This study examined the contribution of lifestyle factors to systolic, diastolic, and mean arterial pressure (MAP) among people living with HIV and cocaine users from racially and ethnically diverse backgrounds.Participants (N = 401: 213 men, 188 women) aged 18 to 50 years with no history of CVD were recruited from South Florida. A total of 200 participants were HIV-cocaine-infected, 100 were HIV-infected individuals with no history of cocaine use, and 101 were HIV-uninfected individuals with cocaine abuse or dependence. Carotid intima-media thickness and plaque, blood pressure (BP), and lifestyle risk were assessed.Mean age was 36 years (standard deviation 9.33); the majority (62%) were African American. Carotid plaques were identified in 23% of participants; 42% were obese, 68% engaged in ≥150 minutes of weekly exercise, and 68% were smokers. Sex, body mass index (BMI), and diet were associated with systolic BP. Age, BMI, cannabis use, and diet were associated with diastolic BP and MAP.Age, BMI, cannabis use, and diet were associated with increased diastolic BP and MAP. Cocaine did not emerge as a significant predictor of CVD after controlling for cannabis dependence. Cocaine and HIV lacked significant association with CVD, possibly because the majority of the sample was younger than age 40. Lifestyle modifications and substance abuse counseling may be important in preventing CVD among those without a history of CVD.

The recent NIH mandate to consider sex as a biological variable in preclinical research has focused attention on delineation of sex differences in behavior. To investigate mechanisms underlying sex differences in Δ9-tetrahydrocannabinol (THC) effects, we examined the effects of sex and gonadal hormones on CB1 receptors in cerebellum, hippocampus, prefrontal cortex, and striatum.Adult Sprague-Dawley rats underwent gonadectomy (GDX) or sham-GDX. Half of the GDX females and males received estradiol or testosterone replacement (GDX+H), respectively. All rats were injected with vehicle or 30 mg/kg THC twice daily for 1 week before brain collection. CP55,940-stimulated [35S]GTPγS and [3H]SR141716A saturation binding assays were performed.With exception of enhanced receptor activation in the hippocampi of female rats compared to males, vehicle-treated rats exhibited minimal sex differences in CB1 receptor densities or G-protein coupling. Repeated treatment with THC resulted in pronounced CB1 receptor desensitization and downregulation in both sexes in all brain regions with a greater magnitude of change in females.These results suggest that sex differences in the density and G-protein coupling of brain CB1 receptors may play a limited role in sex differences in acute THC effects not mediated by the hippocampus. In contrast, sex differences after repeated THC were common, with females (intact, GDX, and GDX+H) showing greater downregulation or desensitization in all four brain regions compared to the respective male groups. This result is consistent with a finding that women tend to progress to tolerance and dependence quicker than men after initiation of cannabis use.

Approximately one-third of patients with epilepsy presents seizures despite adequate treatment. Hence, there is the need to search for new therapeutic options. Cannabidiol (CBD) is a major chemical component of the resin of Cannabis sativa plant, most commonly known as marijuana. The anti-seizure properties of CBD do not relate to the direct action on cannabinoid receptors, but are mediated by a multitude of mechanisms that include the agonist and antagonist effects on ionic channels, neurotransmitter transporters, and multiple 7-transmembrane receptors. In contrast to tetra-hydrocannabinol, CBD lacks psychoactive properties, does not produce euphoric or intrusive side effects, and is largely devoid of abuse liability.The aim of the study was to estimate the efficacy and safety of CBD as adjunctive treatment in patients with epilepsy using meta-analytical techniques.Randomized, placebo-controlled, single- or double-blinded add-on trials of oral CBD in patients with uncontrolled epilepsy were identified. Main outcomes included the percentage change and the proportion of patients with ≥ 50% reduction in monthly seizure frequency during the treatment period and the incidence of treatment withdrawal and adverse events (AEs).Four trials involving 550 patients with Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS) were included. The pooled average difference in change in seizure frequency during the treatment period resulted 19.5 [95% confidence interval (CI) 8.1-31.0; p = 0.001] percentage points between the CBD 10 mg and placebo groups and 19.9 (95% CI 11.8-28.1; p < 0.001) percentage points between the CBD 20 mg and placebo arms, in favor of CBD. The reduction in all-types seizure frequency by at least 50% occurred in 37.2% of the patients in the CBD 20 mg group and 21.2% of the placebo-treated participants [risk ratio (RR) 1.76, 95% CI 1.07-2.88; p = 0.025]. Across the trials, drug withdrawal for any reason occurred in 11.1% and 2.6% of participants receiving CBD and placebo, respectively (RR 3.54, 95% CI 1.55-8.12; p = 0.003) [Chi squared = 2.53, degrees of freedom (df) = 3, p = 0.506; I2 = 0.0%]. The RRs to discontinue treatment were 1.45 (95% CI 0.28-7.41; p = 0.657) and 4.20 (95% CI 1.82-9.68; p = 0.001) for CBD at the doses of 10 and 20 mg/kg/day, respectively, in comparison to placebo. Treatment was discontinued due to AEs in 8.9% and 1.8% of patients in the active and control arms, respectively (RR 5.59, 95% CI 1.87-16.73; p = 0.002). The corresponding RRs for CBD at the doses of 10 and 20 mg/kg/day were 1.66 (95% CI 0.22-12.86; p = 0.626) and 6.89 (95% CI 2.28-20.80; p = 0.001). AEs occurred in 87.9% and 72.2% of patients treated with CBD and placebo (RR 1.22, 95% CI 1.11-1.33; p < 0.001). AEs significantly associated with CBD were somnolence, decreased appetite, diarrhea, and increased serum aminotransferases.Adjunctive CBD in patients with LGS or DS experiencing seizures uncontrolled by concomitant anti-epileptic treatment regimens is associated with a greater reduction in seizure frequency and a higher rate of AEs than placebo.

Forthcoming legislative changes will legalize and make cannabis widely available in Canada. We conducted an analysis of Ontario's birth registry to determine recent trends and correlates of cannabis use in pregnancy.We conducted a population-based retrospective cohort study assembled from the Better Outcomes Registry & Network (BORN) Ontario database, covering live births and stillbirths in Ontario between April 2012 and December 2017. Trends in self-reported cannabis use in pregnancy were analyzed according to maternal age and area-level socio-economic status (SES) using log binomial regression analysis.A total of 10,731 women reported cannabis use in pregnancy. Prevalence increased from 1.2% in 2012 to 1.8% in 2017 (p-trend, < 0.001), equivalent to a relative increase of 61% (relative risk [RR] 1.61, 95% confidence interval [CI] 1.51 to 1.72). The crude prevalence of cannabis use in pregnancy among women aged 15 to 24 years and in the lowest two area-level income quintiles was 6.7%, compared to 0.3% among women aged 35 years and over in the highest three income quintiles (RR 24.59, 95% CI 21.98 to 27.52). A majority (52.0%) of cannabis users were aged 15-24 years and 54.7% of users were in the lowest two income quintiles.Cannabis use in pregnancy has increased since 2012 in Ontario and was reported in about 2% of pregnancies in 2017. Increases were predominately among women of younger ages and those of lower SES, and these groups account for half of users. Promoting cannabis cessation in pregnancy could lead to improved perinatal and later childhood outcomes and reduce health inequalities.

We review recent findings on medical aspects of marijuana use in order to identify those who are at greatest risk of marijuana-related medical problems. We analyze the impact of medical marijuana laws on health, in particular the disproportionate effects on adolescents and children. Chronic marijuana use predominantly affects certain areas of the brain that overlap the default mode network, linked hubs in the brain that play a supervisory role in critical thought processes such as attention, memory, and social interactions. Disruption of the default mode network areas has been documented in schizophrenia and Alzheimer's disease, illnesses with symptoms and brain changes that parallel findings in marijuana abusers. These findings counter the claim that marijuana is a harmless drug and are a cause for alarm in persons with cannabis dependence.

Cannabis is the most commonly used illicit drug among U.S. adolescents and adults, but little is known about factors that drive trends in cannabis use prevalence. To better understand drivers of these trends, we aimed to estimate age, period, and cohort effects on past-month cannabis use among U.S. individuals age 12 and older from 2002 to 2015.We conducted an age-period-cohort analysis on past-month cannabis use among participants ages 12 and older using the National Survey on Drug Use and Health (NSDUH), an annual cross-sectional nationally-representative survey of drug use. Additionally, we examined how age, period, and cohort effects differed across gender. Participants (n = 779,799) self-reported cannabis patterns using a computer-assisted telephone interview (CATI).Past-month cannabis use in this population increased from 6.0% in 2002 to 8.1% in 2015. Distinct age, period, and cohort effects were observed. Compared to participants ages 12-13, participants ages 18-21 (PR: 16.8, 95% CI: 15.6, 18.1) and 22-25 (PR: 13.2, 95% CI: 12.2, 14.4) had dramatically higher prevalence of past-month cannabis use. Compared to participants in 2002, participants in 2014 (PR: 1.2, 95% CI: 1.1, 1.4) and 2014 (PR: 1.2, 95% CI: 1.1, 1.4) had slightly higher prevalence of past-month cannabis use. Compared to the 1940s birth cohort, the 1950s birth cohort (PR: 1.8, 95% CI: 1.5, 2.2) had a higher prevalence of past-month cannabis use.Past-month cannabis use is prevalent and increasing among U.S. adults. Distinct age, period, and cohort effects are at play, though age effects are strongest.

To examine whether the (a) childhood neighborhood context predicts alcohol use disorder, nicotine dependence, and cannabis use disorder symptoms at the age of 39 years; and (b) socio-economic status during young adulthood mediates these relationships. Gender differences were also examined.The Seattle Social Development Project is a prospective longitudinal study of 808 individuals followed up from ages 10 to 39 years in Seattle, Washington, United States. The sample was gender balanced (51% were men).Alcohol, nicotine, and cannabis use disorder symptoms were assessed using the Diagnostic and Statistical Manual of Mental Disorders IV-based Diagnostic Interview Schedule. Childhood neighborhood data consisted of 10 neighborhood-level variables from the 1990 national census, which were consolidated using principal component analyses. Two components with eigenvalues greater than 1 were extracted-neighborhood disadvantage and neighborhood stability. Educational attainment and employment status represented socio-economic status during young adulthood. Covariates included baseline symptoms of psychopathology, baseline substance use, gender, ethnicity, and childhood socio-economic status at the family level. Negative binomial regression was used as the primary modeling strategy. Six models for each outcome measure were estimated. The first three models examined associations between two neighborhood components and each substance use outcome measure. Next, we tested the second research question by adding unemployment and college graduate indicators at the age of 30 years as potential mediators underlying the link between the childhood neighborhood context and three substance use measures.Study findings revealed that childhood neighborhood stability significantly reduced alcohol and cannabis use disorder symptoms nearly 3 decades later. Path analyses suggested that socio-economic status during the transition to adulthood did not influence these relationships but rather had independent effects on problematic nicotine and cannabis use. Furthermore, the effects of childhood neighborhood factors on problematic nicotine use were stronger for men.Neighborhood characteristics during childhood may be important factors for alcohol and cannabis use disorder symptoms among adults and nicotine dependence disorder symptoms among men. Prevention efforts that address community stability and disadvantage can and should start in childhood, with a focus on intervention targets that might gain salience later in life to discourage the development and persistence of problematic substance use in adulthood.

There is a rapidly evolving legal and medical culture around cannabis, with corresponding changes in the demographics of users. For instance, the percentage of the aging population accessing cannabis is growing substantially, outpacing other age groups. The goals of this study were to describe the acute effects of cannabis, subjective experiences of withdrawal, and beliefs around the addictiveness of cannabis, as well as to determine whether these effects differ as a function of age or reason for use (medical vs. recreational use). It was hypothesized that medical users and younger users would report fewer adverse effects.Survey responses from 2905 cannabis users were analyzed.Hierarchical logistic regression analyses were used to compare group percentages after statistically controlling for confounding differences in their demographic and cannabis use characteristics. The most commonly endorsed acute effects were improved sleep, more calm/peaceful, desire to eat, more creative, and dry mouth; while the most commonly endorsed withdrawal symptoms were irritability, insomnia, and anxiety. Relative to recreational users, medical users were less likely to report undesirable acute effects but were more likely to report undesirable withdrawal symptoms. Older (50+) individuals reported fewer undesirable acute effects and withdrawal symptoms compared with younger users (18-29). Only 17% of the total sample reported believing that cannabis is addictive, and this did not vary as a function of reason for use.Older people and medical users appear to experience acute and withdrawal effects of cannabis differently than recreational and younger users, perhaps because these groups benefit more from the medicinal properties of cannabis. These data can provide descriptive information to help inform health care providers and potential consumers about effects of cannabis use.

Little is known about trends in the treatment of problematic cannabis use in Canada. Trends in treatment utilization for problematic cannabis use were examined, as well as trends in the associated sociodemographic characteristics and frequency of cannabis use.This was a repeated cross-sectional study using data from the Drug and Alcohol Treatment Information System, capturing utilization of all community funded addiction treatment services in Ontario, Canada. Clients in treatment for their own problematic cannabis use from 2010/11 to 2015/16 were included. Two distinct groups were formed: clients with problematic cannabis use only (the cannabis-only group) and clients with problematic use of cannabis and other substances (the cannabis-plus group). Estimates of the number of clients in each of these groups and their cannabis use frequency (past 30 days) were characterized over time by new admissions and total caseload (new admissions plus carryovers).There were 152 984 admissions for 83 621 clients over the study period. The number of clients with new admissions in the cannabis-only group decreased from 2954 (95% confidence interval [CI] 2848-3062) in 2010/11 to 2342 (95% CI 2248-2439) in 2015/16. Similar downward trends were observed in the number of clients in the total caseload of this group. The number of clients with new admissions in the cannabis-plus group was stable, but the total caseload increased from 20 139 clients (95% CI 19 862-20 419) in 2011/12 to 21 816 (95% CI 21 527-22 107) in 2015/16. Proportions of daily cannabis use increased among clients in both groups.The number of clients in treatment for problematic cannabis use only decreased over the study period, but the frequency of cannabis use increased among clients in both groups. Given the potential reductions in treatment that is unnecessary from a clinical standpoint, alignment of treatment programming with disorder severity may be warranted.

There is a growing interest in the use of medical cannabis for a variety of dermatologic conditions. Despite the lack of evidence to validate the effectiveness and safety of marijuana, it is approved to treat a variety of dermatologic conditions in the United States. Furthermore, medical cannabis dispensaries have been making unsubstantiated claims about medical cannabis. It is important for dermatologists to know about the purported use of medical cannabis to help patients navigate this new treatment option, particularly as cannabis becomes legal in Canada in October 2018. We collected and tabulated the dermatologic indications for medical cannabis from Canada, the United States, and Europe. In the United States, dermatologic-approved indications vary by state but include psoriasis, lupus, nail-patella syndrome, and severe pain. Health Canada has listed psoriasis, dermatitis, and pruritus as potential therapeutic uses for cannabis but does not endorse its use for therapeutic purposes. We also surveyed the websites of dispensaries in Canada, the United States, and Europe and found that numerous unsubstantiated claims were being made and advertised to consumers. Dermatologic uses of medical cannabis, as claimed by dispensaries, included treating acne, aging, allergic contact dermatitis, chronic pain, herpes, dermatitis, lupus, Lyme disease, nevi, psoriasis, epidermolysis bullosa, and melanoma. Psoriasis, dermatitis, and chronic pain were the most commonly cited indications for medical cannabis listed by dispensaries. Our data indicate that the suggested and advertised uses of medical cannabis are largely unsubstantiated. Further research is necessary to validate the indications, effectiveness, and safety of medical cannabis.

Cessation from prolonged use of ∆9 -tetrahydrocannabinol (THC), the primary active compound responsible for the cannabimimetic effects of cannabis, results in a mild to moderate withdrawal syndrome in humans and laboratory animals. Whereas manipulations of the endogenous cannabinoid system (eg, cannabinoid receptors and endocannabinoid regulating enzymes) alter nicotine withdrawal, in this study we asked the reciprocal question. Do nicotinic acetylcholine receptors (nAChRs) modulate THC withdrawal? To assess the role of different nAChR subtypes in THC withdrawal, we used transgenic mouse, preclinical pharmacological, and human genetic correlation approaches. Our findings show that selective α3β4* nAChR antagonist, AuIB, and α3β4* nAChR partial agonist, AT-1001, dose-dependently attenuated somatic withdrawal signs in THC-dependent mice that were challenged with the cannabinoid-1 receptor antagonist rimonabant. Additionally, THC-dependent α5 and α6 nAChR knockout (KO) mice displayed decreased rimonabant precipitated somatic withdrawal signs compared with their wild-type counterparts. In contrast, β2 and α7 nAChR KO mice showed no alterations in THC withdrawal signs. Moreover, deletion of β2 nAChR did not alter the reduced expression of somatic signs by the preferred α6β4* antagonist, BulA [T5A;P60]. Finally, the human genetic association studies indicated that variations in the genes that code for the α5, α3, β4, and α6 nAChRs were associated with cannabis disorder phenotypes. Overall, these findings suggest that α3β4* and α6β4* nAChR subtypes represent viable targets for the development of medications to counteract THC dependence.

Tobacco and cannabis co-users (T+CUs) have poor cannabis cessation outcomes, but the mechanisms underlying this are not well understood. This laboratory study examined the effects of (1) the partial nicotinic agonist, varenicline, on tobacco cessation among T+CUs, and (2) varenicline, alone, and when combined with the cannabinoid agonist nabilone, on cannabis withdrawal and a laboratory model of cannabis relapse. Non-treatment-seeking T+CUs were randomized to active-varenicline or placebo-varenicline, and completed a 15-day outpatient phase; varenicline was titrated to 1 mg BID during days 1-8, and participants were instructed to abstain from tobacco during days 9-15. Participants then moved inpatient for 16 days, where they continued their outpatient medication and tobacco abstinence. Inpatient testing included two, 8-day medication periods, where active-nabilone and placebo-nabilone were administered in counterbalanced order, and measures of acute cannabis effects (days 1-2), withdrawal (days 4-5) and 'relapse' (days 6-8) were collected. Participants in the active-varenicline group were more likely to achieve cotinine-verified tobacco abstinence during the outpatient period versus placebo-varenicline group (46 percent versus 24 percent, respectively), and also reported less mood disturbance and cigarette craving while inpatient. Active-nabilone attenuated cannabis withdrawal in both groups but did not affect cannabis relapse. Regression analyses revealed that two tobacco-related variables, i.e. age of first cigarette use, and cigarette craving while inpatient, were independent predictors of cannabis relapse outcomes. Thus, varenicline holds promise in this population, as a tool to examine the effects of tobacco abstinence on cannabis use outcomes, and as a component of smoking cessation treatments targeting T+CUs.

The effects and side effects of medical cannabis are not well-established. In 2018, cannabis was approved as a medical drug in Denmark - giving all doctors the opportunity to subscribe medical cannabis to their patients. In this case report a 64-year-old kidney-transplanted woman started cannabis droplets due to chronic back pain, which resulted in increased appetite, weight gain and development of diabetes mellitus. Patients with an increased risk of developing diabetes may be more prone to this under the treatment with cannabis. Further studies are needed.

An association between borderline personality disorder (BPD) and substance use disorders has been well established. However, very little is known about the relationship between BPD and prescription opioid misuse, specifically.The relationship between borderline personality disorder features and prescription opioid misuse was examined in a sample of 208 substance use disorder treatment patients in the outpatient level of care.Controlling for use of alcohol and cannabis, as well as other relevant covariates, we found that BPD features were associated with age of first use of prescription opioids, prescription opioid use disorder symptom count, lifetime use, past 12-month use, problem use, and cravings. Additionally, we found that BPD features were not associated with greater use of medically necessary opioid pain killers as prescribed by a physician; rather the association with BPD was in the greater likelihood of misuse (non-prescribed) of prescription opioid pain killers. The self-harm/impulsivity facet of BPD was most strongly associated with prescription opioid-related variables. Conclusions/Importance: These findings suggest that BPD is related to prescription opioid misuse, above and beyond the tendency to use other drugs of abuse, and that the self-harm impulsivity facet appears to be driving this relationship.

Cannabinoids are the most commonly abused illicit drugs worldwide. While cannabis can be beneficial for certain heath conditions, abuse of potent synthetic cannabinoids has been on the rise. Exposure to cannabinoids is also prevalent in women of child-bearing age and pregnant women. These compounds can cross the placental barrier and directly affect the fetus. They mediate their effects primarily through G-protein coupled cannabinoid receptors, CB1 and CB2. In addition to significant neurological effects, cannabinoids can trigger robust immunomodulation by altering cytokine levels, causing apoptosis of lymphoid cells and inducing suppressor cells of the immune system. Profound effects of cannabinoids on the immune system as discussed in this review, suggest that maternal exposure during pregnancy could lead to dysregulation of innate and adaptive immune system of developing fetus and offspring potentially leading to weakening of immune defenses against infections and cancer later in life. Emerging evidence also indicates the underlying role of epigenetic mechanisms causing long-lasting impact following cannabinoid exposure in utero.

Self-induced dermatoses are more and more frequent in adolescent substance abusers with adaptation problems. We here report a case of self-induced bullous lesions on the shoulder in an adolescent with major depression and suicidal ideations. The study involved a 22-year old man, who was a chronic smoker, an occasional user of cannabis and alchool with no particular past medical history, with divorced parents, in conflict with his father. He presented with bullous eruption on the left shoulder made of bubbles, post-bullous skin erosions and scabs on a healthy skin. The monomorphic appearance of lesions, their accessibility (on the left shoulder in a right-handed patient), patient's history and his psychiatric problems have immediately suggested the investigation of self-induced dermatosis or factitious disorder. The patient admitted that he had taken psychotropic drugs and that the self-induced lesions had been caused by cigarette burns. This first psichologic evaluation also showed that the patient had suicidal ideations and a self-and hetero-aggressive behavior. The patient was treated with emollients and healing creams and referred to the Department of Psychiatry for complementary therapies.

Blood-sucking phlebotomine sand flies (Diptera: Psychodidae) transmit leishmaniasis as well as arboviral diseases and bartonellosis. Sand fly females become infected with Leishmania parasites and transmit them while imbibing vertebrates' blood, required as a source of protein for maturation of eggs. In addition, both females and males consume plant-derived sugar meals as a source of energy. Plant meals may comprise sugary solutions such as nectar or honeydew (secreted by plant-sucking homopteran insects), as well as phloem sap that sand flies obtain by piercing leaves and stems with their needle-like mouthparts. Hence, the structure of plant communities can influence the distribution and epidemiology of leishmaniasis. We designed a next-generation sequencing (NGS)-based assay for determining the source of sand fly plant meals, based upon the chloroplast DNA gene ribulose bisphosphate carboxylase large chain (rbcL). Here, we report on the predilection of several sand fly species, vectors of leishmaniasis in different parts of the world, for feeding on Cannabis sativa We infer this preference based on the substantial percentage of sand flies that had fed on C. sativa plants despite the apparent "absence" of these plants from most of the field sites. We discuss the conceivable implications of the affinity of sand flies for C. sativa on their vectorial capacity for Leishmania and the putative exploitation of their attraction to C. sativa for the control of sand fly-borne diseases.

Catatonia is frequently associated with mood and psychotic disorders as well as with general medical conditions, especially with seizures. In the case of the latter, catatonia mostly resolves when the seizures respond to the anticonvulsive treatment. We report, to our knowledge, the first case of a patient without affective or psychotic disorder, who developed catatonia in the postictum and whose catatonia did not resolve with anticonvulsive treatment, but did so with lorazepam.We describe a 36-year-old man, with no psychiatric history, except for a possible disorder in the use of cannabis, who developed catatonia after epileptic seizures. The catatonia did not respond to the anticonvulsant therapy, but did so to lorazepam 17 mg/d. Lorazepam could be tapered slowly and stopped without reemergence of catatonic signs.Catatonia should be part of the differential diagnosis in patients with bradyphrenia and/or remarkable postictal behavior. This report shows that lorazepam should be taken into consideration (before moving to ECT), in cases of unresolved catatonia, even if the seizures are reduced with anticonvulsants.

This study was conducted to review the current state of evidence on the association between age of initiation of cannabis use and symptoms of psychosis, depression, or anxiety among youth under 25 years of age.We conducted a systematic review of articles published prior to March 2018 by searching OVID MEDLINE, PsycINFO, EMBASE, and the references of included studies. We included comparative studies (cohort, case-control, cross-sectional) that reported on cannabis use in persons <25 years of age (exposure) and symptoms of psychosis, depression, or anxiety (outcome). We narratively synthesized the studies according to design (cohort, etc.) and psychiatric outcome. We used the Newcastle-Ottawa Scale to assess risk of bias.Of the 534 citations identified through the literature search, 23 met the eligibility criteria and were included in this review. With psychosis as the outcome, all except one study found that earlier cannabis use was generally associated with higher risks. With depression/anxiety as the outcome, 6 of the 11 included studies reported findings indicating that earlier use of cannabis was linked to higher symptom levels.In persons <25 years old, greater cannabis use is associated with more psychological symptoms, especially among those with a predisposition or existing vulnerability to such outcomes (Oxford Centre for Evidence-Based Medicine level 3 or 4). Policy makers need to consider the adverse effects of cannabis use in youth when planning a public health approach to cannabis legalization.

Daily cannabis use can portend problematic use or dependence. We aimed to identify early risk factors for daily cannabis use in young adults.Data were available in a longitudinal investigation of 1294 grade 7 students age 12 to 13 years at inception recruited in 10 secondary schools in Montreal, Canada, in 1999. Data on daily cannabis use were collected in mailed self-report questionnaires from 878 participants (67.9% of 1294) at age 20. The associations between each of 23 potential risk factors measured in grade 7 and daily cannabis use at age 20 were modeled using logistic regression.At age 20, 44% of participants reported past-year cannabis use; 10% reported daily use. Older age; male sex; higher levels of family stress and other stress; use of alcohol, cigarettes, and other tobacco products; parent(s), sibling(s), and friend(s) smoke cigarettes; higher body mass index; higher impulsivity and novelty seeking; and lower self-esteem increased the odds of daily cannabis use.Children at risk of daily cannabis use as young adults can be identified early. They may benefit from early intervention to prevent problematic cannabis use.

Chronic exposure to alcohol and other drugs of abuse has been associated with deleterious consequences, including functional connectivity deficits within neural networks associated with executive control. Altered functional connectivity within the executive control network (ECN) might underlie the progressive inability to control consumption of alcohol and other drugs as substance use disorders progress. Genetic and epigenetic factors have been associated with substance use disorders (SUDs). For example, dopamine receptor 2 (DRD2) functioning has been associated with alcohol use disorder (AUD) and related phenotypes, including correlates of executive functioning. The present study aims to explore the relationship between a continuous measure of alcohol-related problems, epigenetic markers (methylation) within the DRD2 gene, and functional connectivity within the ECN among a sample of polysubstance users. A community sample of 658 subjects, whose consumption of alcohol, nicotine, and cannabis span across a spectrum of quantity and frequency of use, were obtained across previous studies in polysubstance using populations. Resting state functional magnetic resonance imaging was analyzed to identify intrinsic connectivity networks using a priori regions of interest. Methylation measurement of functionally relevant sites within the DRD2 gene was achieved via pyrosequencing. Regression-based models, including mediation and moderation models, tested the association between DRD2 methylation, functional connectivity within intrinsic neural networks (including the ECN), and severity of alcohol problems. Results suggest that average DRD2 methylation was negatively associated with right ECN (RECN) and left ECN (LECN) connectivity, but not associated with other networks tested, and DRD2 methylation was significantly associated with alcohol problems severity. Mediation models were not supported, although moderation models suggested that connectivity between edges within the RECN moderated the relationship between DRD2 methylation and AUD severity. Results support a theoretical model in which epigenetic factors are associated with neurobiological correlates of alcohol consumption among a sample of polysubstance users.

Traditional Chinese medicines (TCMs), particularly the Chinese herbal medicines, are valuable sources of medicines and have been used for centuries. The term "TCMs" both represents to the single drug agent like Salvia miltiorrhiza, Ligusticum chuanxiong and Angelica sinensis, and those herbal formulas like Jingshu Keli, Wenxin Keli and Danzhen powder. In recent years, the researches of TCMs developed rapidly to understand the scientific basis of these herbs. In this review, we collect the studies of TCM and their containing bioactive compounds, and attempt to provide an overview for their regulatory effects on different ion channels including Ca2+, K+, Na+, Cl- channels and TRP, P2X receptors. The following conditions are used to limit the range of our review. (i) Only the herbal materials are included in this review and the animal- and mineral-original TCMs are excluded. (ii) The major discussions in this review focus on single TCM agent and the herbal formulas are only discussed for a little. (iii) Those most famous herbal medicines like Capsicum annuum (pepper), Curcuma longa (ginger) and Cannabis sativa (marijuana) are excluded. (iv) Only those TCM herbs with more than 5 research papers confirming their effects on ion channels are discussed in this review. Our review discusses recently available scientific evidences for TCMs and related bioactive compounds that have been reported with the modulatory effects on different ion channels, and thus provides a new ethnopharmacological approach to understand the usage of TCMs.

The World Health Organization's (WHO's) proposed International Classification of Diseases, 11th edition (ICD-11) includes several major revisions to substance use disorder (SUD) diagnoses. It is essential to ensure the consistency of within-subject diagnostic findings throughout countries, languages and cultures. To date, agreement analyses between different SUD diagnostic systems have largely been based in high-income countries and clinical samples rather than general population samples. We aimed to evaluate the prevalence of, and concordance between diagnoses using the ICD-11, The WHO's ICD 10th edition (ICD-10) and the Diagnostic and Statistical Manual of Mental Disorders, 4th and 5th editions (DSM-IV, DSM-5); the prevalence of disaggregated ICD-10 and ICD-11 symptoms; and variation in clinical features across diagnostic groups.Cross-sectional household surveys.Representative surveys of the general population in 10 countries (Argentina, Australia, Brazil, Colombia, Iraq, Northern Ireland, Poland, Portugal, Romania and Spain) of the World Mental Health Survey Initiative.Questions about SUDs were asked of 12 182 regular alcohol users and 1788 cannabis users.Each survey used the World Mental Health Survey Initiative version of the WHO Composite International Diagnostic Interview version 3.0 (WMH-CIDI).Among regular alcohol users, prevalence (95% confidence interval) of life-time ICD-11 alcohol harmful use and dependence were 21.6% (20.5-22.6%) and 7.0% (6.4-7.7%), respectively. Among cannabis users, 9.3% (7.4-11.1%) met criteria for ICD-11 harmful use and 3.2% (2.3-4.0%) for dependence. For both substances, all comparisons of ICD-11 with ICD-10 and DSM-IV showed excellent concordance (all κ ≥ 0.9). Concordance between ICD-11 and DSM-5 ranged from good (for SUD and comparisons of dependence and severe SUD) to poor (for comparisons of harmful use and mild SUD). Very low endorsement rates were observed for new ICD-11 feature for harmful use ('harm to others'). Minimal variation in clinical features was observed across diagnostic systems.The World Health Organization's proposed International Classification of Diseases, 11th edition (ICD-11) classifications for substance use disorder diagnoses are highly consistent with the ICD 10th edition and the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV). Concordance between ICD-11 and the DSM 5th edition (DSM-5) varies, due largely to low levels of agreement for the ICD harmful use and DSM-5 mild use disorder. Diagnostic validity of self-reported 'harm to others' is questionable.

Adults with medical multimorbidity (≥2 chronic conditions) present challenges for health care systems to provide coordinated care. Substance use can complicate the management of chronic medical conditions, but little research has focused on the intersection of medical multimorbidity and substance use. This study uses cross-sectional analysis of 115,335 adult respondents of the 2012-2014 administrations of the National Survey on Drug Use and Health to estimate the prevalence and correlates of past-year drug use among adults with multimorbidity. The prevalence of past-year drug use was compared between individuals reporting 0, 1, and ≥2 chronic medical conditions. We used multivariable logistic regression to determine correlates of past-year drug use among adults with ≥2 chronic medical conditions. 53.1% reported no chronic conditions, 29.5% reported one chronic condition, and 17.4% reported ≥2 chronic conditions. Past-year drug use was reported by 18.3% of those with no chronic conditions, 14.8% with 1 chronic condition, and 11.6% with ≥2 chronic conditions. Cannabis and opioid analgesics (nonmedical use) were the most common drugs used across all three groups. In the adjusted model, among adults with medical multimorbidity, adults with past-year drug use were more likely to be younger, male, have lower income, and report current tobacco use, alcohol dependence, past-year depression, and having received mental health treatment in the past year. In this national cohort, fewer adults with multimorbidity reported substance use compared to adults with no or one chronic condition, however, this population with high multimorbidity may be particularly vulnerable to the negative effects of drug use.

Introduction Early adolescence is a critical period usually associated with experimentation with illicit substances. In Tunisia few studies explored these risk behaviors among young adolescents. Aims To evaluate the prevalence and the predictors of the use of illicit substances among the young adolescents of Sousse. Methods A cross-sectional study was conducted in the region of Sousse, Tunisia during the 2013/2014 school year among 4272 schoolchildren in 16 public middle schools. Data about psychosocial characteristics and risk behaviors among the schoolchildren, their parents, their siblings and their friends were collected anonymously using a self-administrated questionnaire. Results Females represented 50.5% of participants. The mean age of schoolchildren was 13.3 (±1.2) years. Lifetime illicit substances use prevalence was 2.9% [confidence interval (CI) 95%: (2.4%-3.4%)] and lifetime use of tobacco prevalence was 12.9% [CI 95%: (11.9%-13.9%)]. The age of tobacco onset was significantly younger to the age of experimentation with illicit substances. Insomnia, sadness and illicit substances use among peers were associated with illicit substances use among participants. While the most influential risk factor on illicit substances use was current cigarette smoking with an adjusted odds ratio (OR) of 7.2 [CI 95%: (4.5-11.2)]. Conclusion A national substances use prevention program should be implemented in the schools of Tunisia with an emphasis on tobacco use prevention.

The Affordable Care Act (ACA) offered an unprecedented opportunity to expand insurance coverage to patients with substance use disorders (SUDs). We explored the expectations of key stakeholders for the ACA's impact on SUD care, and examined how clinical characteristics of newly enrolled patients with SUD in a large healthcare delivery system differed pre- and post- ACA implementation.In this mixed-methods study, qualitative interviews were conducted with health system leaders to identify themes regarding how the health system prepared for the ACA. Electronic health record data were used to examine demographics, as well as specific SUD, psychiatric, and medical diagnoses in cohorts of pre-ACA (2012, n = 6066) vs. post-ACA (2014, n = 7099) newly enrolled patients with SUD. Descriptive statistics and logistic regression models were employed to compare pre-ACA and post-ACA measures.Interviewees felt much uncertainty, but anticipated having to care for more SUD patients, who might have greater severity. Quantitative findings affirmed these expectations, with post-ACA SUD patients having higher rates of cannabis and amphetamine use disorders, and more psychiatric and medical conditions, compared to their pre-ACA counterparts. The post-ACA SUD cohort also had more Medicaid patients and greater enrollment in high-deductible plans.Post-ACA, SUD patients had more comorbidities as well as and more financial barriers to care. As federal healthcare policy continues to evolve, with potentially more restrictive coverage criteria, it is essential to continue examining how health systems adapt to changing health policy and its impact on SUD care.

Based on the prevalence and health implications of tobacco and cannabis use, aiming to reduce their use, especially among youth, is a sound objective at both the individual and public health level. A proper understanding of the relationships between tobacco and cannabis use may help to achieve this goal.To review the relationships between tobacco and cannabis use.A selective review of the literature.We present an overview of the motivations for tobacco and cannabis use, and their perceived harmfulness. The article then reviews the gateway theory, reverse gateway theory, route of administration theory, and common liability theory. We describe the link between co-use and dependence symptoms, and the substitution phenomenon between tobacco and cannabis use. Three forms of simultaneous use-mulling, blunt smoking, and chasing-and their impacts are explained. We summarize the impact of tobacco use on cannabis (and vice versa) treatment outcomes, and, finally, review new treatments that simultaneously target tobacco and cannabis dependence. Most of the literature reviewed here relates to substance use among adolescents and young adults.The use of tobacco and cannabis-two of the most widely used substances around the world-are strongly intertwined in several respects. Both health professionals and researchers should have well-informed views on this issue to better evaluate, understand, inform, and provide care to their patients.

About 30% of regular cannabis users report withdrawal symptoms on cessation of prolonged use, such as irritability, insomnia, decreased appetite, depressed mood, anxiety, and restlessness. However, among highly dependent and/or in-treatment users, the incidence of withdrawal can be even higher, reaching up to 50-95% of individuals. This syndrome was only recognized by the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) as a diagnosis with specific criteria in 2013. The treatment options are poor, with high rates of relapse and non-responders. In this scenario, agonist replacement therapy with cannabinoids has demonstrated potential as a promising therapeutic intervention, with a series of studies having been carried out in recent years.This review sought to summarize trials with cannabinoid agonist replacement therapy for cannabis withdrawal symptoms with the aim of evaluating the efficacy of this pharmacological intervention.We entered the following search terms on the PubMed, Web of Science and PsycINFO databases: (marijuana OR marihuana OR cannabis OR THC OR tetrahydrocannabinol OR hashish OR pot) AND (treatment OR medication) AND (withdrawal OR abstinence) AND (dronabinol OR nabilone OR nabiximols OR sativex OR cesamet OR synthetic cannabinoid). The date of the most recent search was September 2017.Original trials, published in English, performed on humans and dealing with cannabis users who were treated for cannabis withdrawal symptoms using synthetic cannabinoids were all included in the present systematic review. Quality and risk of bias across studies were assessed using a Cochrane tool.The first, second, and last authors read the abstracts of all studies found in the search (n = 243). The inclusion and exclusion criteria were applied, and 233 articles were excluded. The first and second authors independently developed a data extraction sheet based on the included articles.The present review included ten original articles. Despite the limited number of studies and methodological differences, our findings demonstrate that the use of dronabinol, nabilone, or nabiximols, either alone or in combination with other drugs, shows promise in reducing cannabis withdrawal symptoms, probably with a dose-dependent effect. This has also been considered a safe group of medications with good tolerability and few adverse effects.No method of handling data and combining results of studies was carried out, representing a limitation of the review.Cannabinoids appear to be a promising group of drugs for the treatment of cannabis withdrawal symptoms. These medications may help decrease the rate of relapse in the treatment of cannabis dependence due to withdrawal symptoms occurring within the first few weeks of treatment.The protocol for this review has been registered in the PROSPERO International prospective register of systematic reviews (PROSPERO 2014:CRD42014014118).

Cannabis withdrawal syndrome (CWS) was newly added to the Diagnostic and Statistical Manual of Mental Disorders in its most recent edition, DSM-5. With cannabis use increasing among U.S. adults, information is needed about the prevalence and correlates of DSM-5 CWS in the general population. This study presents nationally representative findings on the prevalence, sociodemographic and clinical correlates of DSM-5 CWS among U.S. adults.Participants ≥18 years were interviewed in the National Epidemiologic Survey on Alcohol and Related Conditions-III (NESARC-III) in 2012-2013. Among the sub-sample of frequent cannabis users in the prior 12 months (≥3 times a week; N = 1527), the prevalence and demographic and clinical correlates of DSM-5 CWS were examined.In frequent cannabis users, the prevalence of CWS was 12.1%. The most common withdrawal symptoms among those with CWS were nervousness/anxiety (76.3%), hostility (71.9%), sleep difficulty (68.2%) and depressed mood (58.9%). CWS was associated with significant disability (p < 0.001), and with mood disorders (adjusted odds ratios [aOR] = 1.9-2.6), anxiety disorders (aOR = 2.4-2.5), personality disorders (aOR = 1.7-2.2) and family history of depression (aOR = 2.5) but not personal history of other substance use disorders or family history of substance use problems.CWS is highly comorbid and disabling. Its shared symptoms with depressive and anxiety disorders call for clinician awareness of CWS and the factors associated with it to promote more effective treatment among frequent cannabis users.

Recreational cannabis is being legalized in states across the USA. The public relies on popular media for health information about cannabis. We assessed the accuracy of reporting on health effects of cannabis use in GreenState, a specialty publication on cannabis published by the San Francisco Chronicle and the main newspaper using the Index of Scientific Quality for Health Related News Reports. Results were compared using t-tests. Seventeen GreenState articles and four San Francisco Chronicle articles were identified for analysis. Health articles in GreenState scored 2.9 (±1.1 [SD]) Global, with the highest scoring category Applicability (4.5 ± 0.4) and the lowest Precision (2.4 ± 1.0) on a scale of 1-5. In contrast, the San Francisco Chronicle articles received a Global rating of 4.6 (±0.2), ranging from Applicability (5.0 ± 0) to Benefits (3.8 ± 0.9). Articles in the San Francisco Chronicle scored significantly higher in all categories but Benefits which was not significantly different for the San Francisco Chronicle compared with GreenState (3.8 vs. 3.6, p = 0.77). The public, clinicians, and policymakers need to be aware of this pattern and treat information in publications like GreenState with an appropriate level of skepticism until the quality of reporting improves to general journalistic standards.

There are numerous reports of the psychiatric effects of anabolic-androgenic steroid (AAS) use. However, these effects have not been clearly elicited in controlled clinical trials. This discrepancy is largely due to the presence of a variety of synergistic factors seen in the real-life setting of AAS abuse. In this case, we report a patient in acute mania admitted to Frederick Memorial Hospital in Frederick, Maryland. He had no prior history or family history of manic episodes. His symptoms were refractory to initial pharmacologic intervention. The onset of his symptoms was likely related to the initiation of AAS use. However, his symptoms were likely potentiated by heavy daily cannabis use. The patient showed a gradual improvement over the second week of his hospitalization. He was discharged on antipsychotics and scheduled to follow up with a therapist and psychiatrist.

Illicit drug use is common in U.S. medical settings. A validated Single Drug Screening Question (SDSQ) containing the word "illegal" is widely used. As marijuana policies change, the present wording may not perform as expected in states legalizing use. This study compares the performance of the validated SDSQ with three different SDSQ wordings.Patients, 18 years and older, presenting to a U.S. hospital emergency department were asked to complete a survey containing the existing SDSQ, three new SDSQ versions without the word "illegal," and the Mini International Neuropsychiatric Interview. Patients were also encouraged to provide a sample for saliva drug testing.Of 297 eligible patients, 200 (67.3%) completed the survey and 141 (70.5% of interview participants) completed saliva testing. Overlapping confidence intervals on the Area Under the Curve (AUC) analysis confirmed that sensitivities of all SDSQs were statistically similar for detecting self-reported drug use (65-71%). Combining questionnaire and saliva testing increased drug use detection by 2% and resulted in lower SDSQ sensitivity (58-67%). Specificities were 99-100%. The SDSQ with the highest sensitivity was: "In the last twelve months, did you smoke pot (marijuana), use another street drug, or use a prescription medication "recreationally" (just for the feeling, or using more than prescribed)?"All four SDSQs demonstrated acceptable sensitivity and high specificity. Removing the term 'illegal' does not result in higher, or lower, reported drug use, though results could vary in states with legalized marijuana. Future research should replicate this study in one or more of these states.

Several countries are legalizing the use of medicinal cannabis and easing restrictions on its recreational use. While adults have been the primary target of these initiatives, expanding access to cannabis will likely lead to increased use by children. While the effects of cannabis on pediatric neuropsychological and mental health outcomes have been broadly studied, there are limited data on the physical health effects of cannabis, including endocrine health. Animal studies have shown that chronic cannabis use leads to delayed sexual maturation; however, its effects on pubertal outcomes in children are not well studied. This systematic review aimed to assess the effect of cannabis use on pubertal timing and tempo in children.We conducted a systematic review with literature searches in MEDLINE, Embase, Cochrane Database of Systematic Reviews, Central, PsycINFO, CINAHL, Web of Science, and SPORTDiscus from inception to February 2018. A gray literature search was also completed in Clinicaltrials.gov and ProQuest Dissertations and Theses A&I. The primary outcome was pubertal timing, while secondary outcomes included pubertal tempo and final height and weight. We had no restrictions on date or language of publication of papers. Two reviewers independently assessed records for eligibility, with a third reviewer resolving disagreements.Our database and gray literature searches identified 759 records. A total of 29 full-text papers were assessed for eligibility. However, all studies were ultimately excluded as they did not meet the eligibility criteria.Our results highlight a significant gap in existing literature regarding the effects of cannabis use on puberty. Adequately powered longitudinal studies are urgently needed to provide pediatricians and other health care providers with high-quality information on the potential effects of cannabis on the physical health of children.PROSPERO no.: CRD42018089397.

Cannabis is reported to be the most common illicit substance used among medical students; however, the number of related studies is limited and their results are not systematically reviewed. The aim of our study was to analyze the prevalence of lifetime and current use of cannabis among medical students worldwide.A systematic review and meta-analysis was performed with adherence to the PRISMA guidelines. The electronic databases PubMed, Scopus, and Cochrane library were searched for studies on the prevalence of cannabis use among medical students. Prevalence of lifetime, past-year, and past-month cannabis use was extracted. Pooled prevalence and relative risk for sex were calculated using the random effects model and subgroup analyses were conducted.A total of 38 observational (cross-sectional and cohort) studies were included (total number of participants 19 932), and most of them were conducted in Europe, Central and Southern America, and the United States. Overall pooled prevalence of lifetime cannabis use was 31.4% (95% confidence interval [CI]: 23.7%-39.6%), past-year use was 17.2% (95% CI: 10.8%-24.6%), and past-month use was 8.8% (95% CI: 5.6%-12.5%). Men displayed higher rates of cannabis use with a pooled relative risk of 1.55 (95% CI: 1.32-1.81). Heterogeneity was high (I2 > 75%) and there were differences among continents in all outcomes (P < .001).In conclusion, 1 in 3 medical students has used cannabis, whereas 8.8% were current users. Significant differences among continents were observed, but common finding was that male students tend to consume cannabis more often than female students.

Nowadays, Gas Chromatography Mass Spectrometry (GC-MS) is mainly used in forensic sciences but suffers from limitations when the analysed compounds are thermally instable as it is the case for THC-A (Tetrahydrocannabinolic Acid) which is converted into Δ9-THC (Δ9-Tetrahydrocannabinol) that subsequently partially degrades. We propose herein a Fast High Pressure Liquid Chromatography (Fast-HPLC-DAD) method which allows the efficient separation of CBN (Cannabinol), CBD (Cannabidiol), THC-A and Δ9-THC, the major cannabinoids compounds found in cannabis plants in less than 5 min. Our method allows also the proper quantification of Δ9-THC in plant extracts using an external calibration method with a very good accuracy as pointed out by a recovery of 100.53 ± 3.12%. It is also an interesting low cost alternative to Ultra High Pressure Liquid Chromatography (UPLC) for routine analyses in forensic sciences.

Pharmacological neuroenhancement (PNE) refers to the use of psychoactive substances without doctor's prescription to enhance cognitive performance or to improve mood. Although some studies have reported that drugs for PNE are also being used to cope with stressful life situations, nothing is known about the relationship of PNE and resilience, i.e. the ability to recover from stress. This study aimed at investigating the relationship of PNE and resilience in the first representative population sample.A cross-sectional survey in a representative sample of 1128 adults (age ≥ 18 yrs.) living in Germany was conducted. The use of PNE and related attitudes, perceptions and behaviours were assessed by structured interviews and self-report questionnaires. Stepwise logistic regression with backward elimination was conducted to identify potential risk factors for PNE use.Lifetime prevalence for the use of stimulating prescription drugs without medical indication was 4.3%, 10.2% for stimulating illicit drugs, 20.3% for mood modulating prescription drugs, and 23.4% for cannabis. Coping with stressful situations was more frequently reported as underlying motive for using stimulant or mood modulating prescription drugs than stimulating illicit drugs or cannabis. The individual perceived stress increased the risk of using stimulating prescription drugs (OR: 2.86; 95% Cl: 1.49-5.46) and the individual ability to recover from stress decreased the risk of using any substance for PNE and especially mood modulating prescription drugs (OR: .62; 95% Cl: .47-.81).The non-medical use of prescription drugs for PNE appears to be more prevalent in subjects who are less resilient to stress. Tailored resilience interventions that improve the ability to adapt to and recover from stressors may prevent the use of prescription medication for PNE. Further research should disentangle the association between psychological resilience and PNE as well as examine the efficacy of resilience interventions in the prevention of PNE.

Small towns in New Zealand have reported high availability of methamphetamine, and conversely a shortage of cannabis. Stakeholders have suggested drug dealers are purposely promoting methamphetamine rather than cannabis.(1) To compare the availability of methamphetamine and cannabis in different size communities; (2) Identify determinants of the high availability of methamphetamine, including low availability of cannabis.An online drug survey was promoted via a broadly targeted Facebook™ campaign. Participants were asked if they lived in a "city", "small town" or "rural area", their drug use patterns, and local drug market characteristics, including current availability. A total of 6311 people completed the survey. Logistic regression models were constructed to identify independent predictors of reporting high availability of methamphetamine, cannabis, ecstasy and LSD respectively, with low availability of cannabis included as a predictor in the non-cannabis markets.Methamphetamine was reported to be more available than cannabis in all regions. Methamphetamine was more available in towns/rural areas than in cities. Significant predictors of high availability of methamphetamine were living in a town/rural area (OR = 1.38), purchasing from a gang member (OR = 1.88), daily methamphetamine use (OR = 2.41), Maori ethnicity (OR = 1.36) and reporting low availability of cannabis (OR = 1.89). Low availability of cannabis was not a predictor of high availability of ecstasy or LSD. Living in a town/rural area was not a predictor of high availability of cannabis, LSD or ecstasy. Purchasing from a gang member was a predictor of high availability of cannabis (OR = 1.80) and LSD (OR = 4.61).Further research is required to identify what causal relationships, if any, there are between the statistical associations of high methamphetamine availability, living in a small town, purchasing from a gang, and low cannabis availability. It may be the case that small towns offer an environment where a gang can control the local drugs market.

The laws governing cannabis are evolving worldwide and associated with changing patterns of use. The main psychoactive drug in cannabis is Δ9-tetrahydrocannabinol (THC), a partial agonist at the endocannabinoid CB1 receptor. Acutely, cannabis and THC produce a range of effects on several neurocognitive and pharmacological systems. These include effects on executive, emotional, reward and memory processing via direct interactions with the endocannabinoid system and indirect effects on the glutamatergic, GABAergic and dopaminergic systems. Cannabidiol, a non-intoxicating cannabinoid found in some forms of cannabis, may offset some of these acute effects. Heavy repeated cannabis use, particularly during adolescence, has been associated with adverse effects on these systems, which increase the risk of mental illnesses including addiction and psychosis. Here, we provide a comprehensive state of the art review on the acute and chronic neuropsychopharmacology of cannabis by synthesizing the available neuroimaging research in humans. We describe the effects of drug exposure during development, implications for understanding psychosis and cannabis use disorder, and methodological considerations. Greater understanding of the precise mechanisms underlying the effects of cannabis may also give rise to new treatment targets.

Previous research indicates that cannabis use is associated with psychotic-like experiences (PLEs). However, it is unclear whether this association results from predispositional (ie, shared genetic) factors or individual-specific factors (eg, causal processes, such as cannabis use leading to PLEs).To estimate genetic and environmental correlations between cannabis use and PLEs, and to examine PLEs in twin and nontwin sibling pairs discordant for exposure to cannabis use to disentangle predispositional from individual-specific effects.In this cross-sectional analysis, diagnostic interviews and self-reported data were collected from 2 separate population-based samples of twin and nontwin sibling pairs. Data from the Human Connectome Project were collected between August 10, 2012, and September 29, 2015, and data from the Australian Twin Registry Cohort 3 (ATR3) were collected between August 1, 2005, and August 31, 2010. Data were analyzed between August 17, 2017, and July 6, 2018. The study included data from 1188 Human Connectome Project participants and 3486 ATR3 participants, totaling 4674 participants.Three cannabis-involvement variables were examined: frequent use (ie, ≥100 times), a DSM-IV lifetime cannabis use disorder diagnosis, and current cannabis use. Genetic and environmental correlations between cannabis involvement and PLEs were estimated. Generalized linear mixed models examined PLE differences in twin and nontwin sibling pairs discordant for cannabis use.Among the 4674 participants, the mean (SD) age was 30.5 (3.2) years, and 2923 (62.5%) were female. Data on race/ethnicity were not included as a covariate owing to lack of variability within the ATR3 sample; among the 1188 participants in the Human Connectome Project, 875 (73.7%) were white. Psychotic-like experiences were associated with frequent cannabis use (β = 0.11; 95% CI, 0.08-0.14), cannabis use disorder (β = 0.13; 95% CI, 0.09-0.16), and current cannabis use (β = 0.07; 95% CI, 0.04-0.10) even after adjustment for covariates. Correlated genetic factors explained between 69.2% and 84.1% of this observed association. Within discordant pairs of twins/siblings (Npairs, 308-324), Psychotic-like experiences were more common in cannabis-exposed individuals compared with their relative who used cannabis to a lesser degree (β ≥ .23, P < .05; eg, frequent and infrequent cannabis-using relatives significantly differed, z = -5.41; P < .001).Despite the strong contribution of shared genetic factors, frequent and problem cannabis use also appears to be associated with PLEs via person-specific pathways. This study's findings suggest that policy discussions surrounding legalization should consider the influence of escalations in cannabis use on traitlike indices of vulnerability, such as PLEs, which could contribute to pervasive psychological and interpersonal burden.

Low levels of distress tolerance have been identified as an important vulnerability factor for negative cannabis outcomes. The current study is the first known experimental manipulation of state distress to test whether distress tolerance interacts with state distress to predict the urge to use cannabis. Current cannabis users (N = 126; 88.9% with cannabis use disorder; 54.0% non-Hispanic Caucasian) were randomly assigned to a distress task condition or neutral (reading) task condition. Participants in the 2 conditions did not differ on distress tolerance, negative affect (NA), or craving at baseline. The distress tolerance × condition interaction significantly predicted task NA, such that low (but not high) distress tolerance was related to greater state NA throughout the task. The distress tolerance × condition interaction significantly predicted cannabis craving during the task, such that the distress condition was related to greater cannabis craving at lower (but not higher) levels of distress tolerance. In the distress condition, those who endorsed coping motives during the task reported lower distress tolerance. Together these findings suggest that individuals with lower distress tolerance experienced greater NA during a laboratory-induced distress and reported greater cannabis craving when NA was greatest during the task. This experimental study adds to a growing, but limited, literature implicating lower levels of distress tolerance to the maintenance and relapse of cannabis use. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

The effect of cannabis use on chronic liver disease (CLD) from Hepatitis C Virus (HCV) infection, the most common cause of CLD, has been controversial. Here, we investigated the impact of cannabis use on the prevalence of CLD among HCV infected individuals.We analyzed hospital discharge records of adults (age ≥ 18 years) with a positive HCV diagnosis. We evaluated records from 2007 to 2014 of the Nationwide Inpatient Sample (NIS). We excluded records with other causes of chronic liver diseases (alcohol, hemochromatosis, NAFLD, PBC, HBV, etc.). Of the 188,333 records, we matched cannabis users to nonusers on 1:1 ratio (4,728:4,728), using a propensity-based matching system, with a stringent algorithm. We then used conditional regression models with generalized estimating equations to measure the adjusted prevalence rate ratio (aPRR) for having liver cirrhosis (and its complications), carcinoma, mortality, discharge disposition, and the adjusted mean ratio (aMR) of total hospital cost and length of stay (LOS) [SAS 9.4].Our study revealed that cannabis users (CUs) had decreased prevalence of liver cirrhosis (aPRR: 0.81[0.72-0.91]), unfavorable discharge disposition (0.87[0.78-0.96]), and lower total health care cost ($39,642[36,220-43,387] versus $45,566[$42,244-$49,150]), compared to noncannabis users (NCUs). However, there was no difference among CUs and NCUs on the incidence of liver carcinoma (0.79[0.55-1.13]), in-hospital mortality (0.84[0.60-1.17]), and LOS (5.58[5.10-6.09] versus 5.66[5.25-6.01]). Among CUs, dependent cannabis use was associated with lower prevalence of liver cirrhosis, compared to nondependent use (0.62[0.41-0.93]).Our findings suggest that cannabis use is associated with decreased incidence of liver cirrhosis, but no change in mortality nor LOS among HCV patients. These novel observations warrant further molecular mechanistic studies.

The unilateral fetal variant of the posterior cerebral artery (FPCA) is characterized by the congenital absence of the P1 arterial segment. The artery of Percheron (AOP) is an uncommon vascular variant, in which a single dominant thalamoperforating arterial trunk arises from one P1 segment, bifurcates, and provides bilateral supply to the paramedian thalami and rostral midbrain.This is a retrospective case study of a 37-year-old man with multiple lifestyle risk factors (chronic marijuana and tobacco abuse), who suffered a thalamomesencephalic stroke, rapidly worsening to comatose state. After restoration of consciousness, he clinically manifested with left paramedian midbrain syndrome. Imaging demonstrated an asymmetric paramedian thalamic infarction with mesencephalon extension, patency of the basilar, vertebral arteries, and left PCA and right-sided FPCA, respectively. Left-sided thalamoperforating arterioles were not differentiated; AOP was inferred. Neither evident clinical source of embolus nor prothrombotic states were found. Mobile cardiac telemetry and transesophageal echocardiography were not available. The diagnosis was established too late for thrombolytic treatment. Anticoagulation was indicated during the acute and subacute stages, followed by low dose of antiplatelet.This uncommon cerebrovascular configuration (FPCA+AOP) might be the fourth case described in the literature. Sustained rehabilitation and abstinence from tobacco and cannabis led to favorable outcomes.

Some observational studies and literature reviews suggest that antipsychotic drug use is associated with loss of grey or white matter in patients with schizophrenia, whereas others have contradicted this finding. Here, I summarize and critique the available evidence and put it in the context of clinical practice. This narrative review pools evidence from observational and experimental studies in humans and animals on the relationship between antipsychotic medication use and brain structure and function in patients with schizophrenia. To summarize, the observational evidence in patients with schizophrenia and the experimental evidence in animals suggest that antipsychotic drugs can cause reductions in brain volume, but differ as to where those effects are manifest. The experimental evidence in patients is inconclusive. There is stronger and more consistent evidence that other factors, such as alcohol and cannabis use, are likely causes of progressive brain changes in schizophrenia. Overall, I argue the case against antipsychotics is not proven and the jury is out on any significance of putative antipsychotic-induced brain changes. Taken in the context of strong evidence from clinical trials that antipsychotic drugs have beneficial effects on symptoms, function, relapse and cognition, and observational evidence that treatment normalizes other imaging indices and reduces mortality, the balance of probabilities is that antipsychotic drugs do not cause adverse structural brain changes in schizophrenia.

Hodgkin lymphoma (HL) is one of the most curable malignancies. Despite its effectiveness, chemotherapy is often associated with adverse events (AEs) such as nausea, anorexia, and impairment of general well-being. Our objective was to assess the extent of medical cannabis use among HL patients and evaluate its efficacy in controlling chemotherapy-related AEs. Patterns of medical cannabis use and efficacy were evaluated using physician-completed application forms, medical files, and patient-completed questionnaires, for all consecutive adult HL patients treated at the Tel-Aviv Medical Center between June 2010 and November 2016. One-hundred and thirty-three patients met the inclusion criteria. The median age of the cohort was 37 years, 53% were male, 46% were diagnosed at an early stage, and 88% achieved a complete response to treatment. Fifty-one patients (38%) used medical cannabis. There were no significant differences in baseline characteristics between cannabis users and nonusers. Cannabis users reported improvement in pain, general well-being, appetite, and nausea in 94, 87, 82, and 79% of cases, respectively. Importantly, 81.5% reported a high overall efficacy of cannabis in relieving symptoms. AEs related to cannabis use itself were mild. Thus, medical cannabis use is prevalent in this HL cohort, and appears to be effective in ameliorating chemotherapy-related AEs.

Coronary lesions characteristics as well as patient thrombogenicity can explain coronary events manifestation. In young patient, local conditions are usually less important and thrombogenicity could play a significant role. Assessing thrombophilia could be justified in young patients and may induce an adapted therapeutic management.We aimed to assess the prevalence of thrombophilia and therapeutic modification in young adults aged≤55 years admitted in our department for ST elevation myocardial infarction (STEMI).From January 2013 to January 2017, data on all patients aged≤55 years with STEMI admitted in emergency were retrospectively retrieved from our database. Thrombophilia investigation was made regarding clinical (with or without cardiovascular risk factors [CVRF]), biological and/or angiographic evaluation.A total of 133 patients aged≤55 years with STEMI were included. Cardiac arrest occurred in 15 patients (11%). One or less CVRF were found in 47 patients (35%). Smoking was reported in 93 patients (70%) and drug addiction (cannabis, cocaine) in 19 patients (14%). A subset of 51 patients (38%) were screened for thrombophilia. Patients with thrombophilia assessment were younger, less active smokers and presented less CVRF than patients without investigation (P<0.001). Single vessel diseased was found in 88 patients (66%). No differences regarding coronary procedural characteristic were found between the two groups. The most frequently encountered aetiology, found in 122 patients (92%), was de novo intra-arterial thrombosis related to atherosclerosis. In patients with thrombophilia assessment (n=51), one or more abnormal biological results was found in 22 patients (43%) and a therapeutic adjustment was made in 6 patients (12%).Thrombophilia screening in young STEMI adults showed an abnormality in 43% of cases. Antithrombotic treatment can be modified after its demonstration.

Pet exposure to marijuana-containing products-both recreational and medicinal-along with exposure to extracts such as cannabidiol is increasing in conjunction with greater accessibility. Cannabis products are even sold for use in pets. In addition, exposure to illegal synthetic cannabinoids remains concerning. Veterinarians need to be able to recognize associated clinical signs and understand when cases have the potential for severity. This article provides a brief history of cannabis along with a review of the endocannabinoid system, common cannabis products, expected clinical signs, and medical treatment approaches associated with cannabis exposure in pets.

This study aimed to investigate the influence of tightened regulations on new psychoactive substances in patients with disorders related to these drugs in Japan.We used a biennial nationwide survey on drug-related psychiatric disorders to examine why individuals who had previously used new psychoactive substances as their primary drug (the drug that had the greatest impact on their psychiatric symptoms) had switched to other drugs, how they had used drugs in the last 12 months and what type of drugs they were now using. We compared the clinical features of these individuals with patients who mainly used new psychoactive substances and had used these drugs at least once in the last 12 months.A total of 2262 people were included, and 399 had used new psychoactive substances. Of those, 71 people had switched to another drug as primary drug, mostly stimulant drugs (35.2%), hypnotics and anxiolytics (15.5%), and cannabis (14.1%) and used these drugs during the previous 12 months. The majority, 53.3%, had switched "because new psychoactive substances were no longer available." In total, 25 people mainly used new psychoactive substances. The group that had changed drugs had more experience of using methamphetamine and were more likely to have abused other drugs before using new psychoactive substances. They had often switched to illegal or prescription drugs after regulations had been tightened.The number of patients abusing new psychoactive substances decreased after drug regulations were tightened, but new psychoactive substances-related problems still exist. It is therefore not enough to tighten regulations. Drug dependence treatment and recovery support are also needed.

Cannabidiol (CBD) and cannabidivarin (CBDV) are natural cannabinoids which are consumed in increasing amounts worldwide in cannabis extracts, as they prevent epilepsy, anxiety, and seizures. It was claimed that they may be useful in cancer therapy and have anti-inflammatory properties. Adverse long-term effects of these drugs (induction of cancer and infertility) which are related to damage of the genetic material have not been investigated. Therefore, we studied their DNA-damaging properties in human-derived cell lines under conditions which reflect the exposure of consumers. Both compounds induced DNA damage in single cell gel electrophoresis (SCGE) experiments in a human liver cell line (HepG2) and in buccal-derived cells (TR146) at low levels (≥ 0.2 µM). Results of micronucleus (MN) cytome assays showed that the damage leads to formation of MNi which reflect chromosomal aberrations and leads to nuclear buds and bridges which are a consequence of gene amplifications and dicentric chromosomes. Additional experiments indicate that these effects are caused by oxidative base damage and that liver enzymes (S9) increase the genotoxic activity of both compounds. Our findings show that low concentrations of CBD and CBDV cause damage of the genetic material in human-derived cells. Furthermore, earlier studies showed that they cause chromosomal aberrations and MN in bone marrow of mice. Fixation of damage of the DNA in the form of chromosomal damage is generally considered to be essential in the multistep process of malignancy, therefore the currently available data are indicative for potential carcinogenic properties of the cannabinoids.

Cannabis is one of the most abused drugs worldwide, with more than 20 million users in the United States (US). As access to cannabis products increases with expanding US legislation and decriminalization of marijuana, emergency physicians must be adept in recognizing unintentional cannabis toxicity in young children, which can range from altered mental status to encephalopathy and coma.We report the case of a 13-month-old female presenting with self-limiting altered mental status and lethargy, with a subsequent diagnosis of tetrahydrocannabinol exposure on confirmatory urine gas chromatography-mass spectrometry. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Considering caretakers rarely report possible cannabis exposure, history-taking must review caretakers' medicinal and recreational drug exposures to prevent inadvertently missing the diagnosis. In the young child with altered mental status, prompt urine screening for cannabinoid detection can prevent further invasive and costly diagnostic investigations, such as brain imaging and lumbar puncture.

New designer drugs, as synthetic cannabinoids (SCs), continuously appear on the market and are booming due to their cannabis-like effect. New generation of smokable SCs, structurally dissimilar from Δ9-tetrahydrocannabinol (THC), have isomers with distinguishable pharmacokinetic parameters and therefore different in vivo effects. The isoforms are misidentified using conventional techniques such as gas or liquid chromatography coupled to mass spectrometry - or tandem mass - spectrometry. The aim of this study was to differentiate three positional isomers (JWH-007, JWH-019 and JWH-122) in single human hair samples, which store numerous substances revealing a way of life and consumption style. Matrix-assisted laser desorption/ionization (MALDI) combined with imaging is an innovative and powerful tool used since few years, especially in forensic research. Herein, we propose an innovative method to monitor the drugs of abuse consumption through direct mapping of the compounds with a high spatial distribution in human hair samples, by state-of-art imaging MALDI-MSn. Three positional SC isomers (JWH-007, JWH-019 and JWH-122) were analysed using high and low fragmentation energy and the resulting MS/MS and even MS3 spectra differentiated the SCs. The MALDI-MS/MS and MS3 imaging was performed on hair soaked in a mixture of the three SCs as well as on hair from self-reported SC user, proving the potential of the technique for a forensic use. Keeping in mind that spatial distribution of organics from whole hair remains a challenge, the described methodology is a very promising analytical tool to probe the consumption of complex drugs and obtain correlation with its origin.

To determine the effect of clinical, socio-demographic, and contextual characteristics on treatment retention in an opioid treatment program (OTP).A retrospective longitudinal review of 851 clients who received methadone at the only state-funded OTP in Spokane County, Washington between 2015 and 2017. A time variable (the number of days in treatment) and a status indicator (to distinguish between clients who dropped out or censored) worked together to define retention in treatment. Our hypothesized covariates included: area deprivation, distance to the OTP, availability of cannabis retail outlets, availability of on-premise and off-premise alcohol outlets, methadone dosage, age, gender, race, and years on treatment. Cox regression within the family of survival analysis was used to model time-to-event data in the presence of censored cases.The median duration of retention was 394 (95%CI = 324-464) days. In the multivariable Cox regression, factors predicting treatment retention were area deprivation (HR = 1.79, 95%CI = 1.02-3.15, p = 0.04), age (HR=0.99, 95%CI=0.98-.99, p = 0.008), dosage of methadone (HR=0.98, 95%CI=0.98-0.98, p < 0.001), and the number of years on treatment (HR=1.12, 95%CI=1.06-1.18, p < 0.001).The findings of this study showed age and methadone dosage were protective factors and area deprivation and years on treatment were risk factors for treatment retention. After dichotomizing methadone dosage, a unique finding of this study was that higher dosage of methadone did not lead to increasingly smaller HRs for dropping out of treatment. Considering that opioid use disorder is a chronic condition, efforts need to be made to target factors associated with retention.

Cannabis stands as the most used illegal drug in the world. Currently there are no pharmacologic alternatives to treat its addiction, so the use of Cannabinoids has been postulated as a therapeutic tool. They would act mainly through decrease in abstinence and craving symptoms but its effectiveness remains unclear.To answer this question we used Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach.We identified seven systematic reviews including 15 studies, of which four were randomized trials. We concluded the use of cannabinoids might result in little or no increase in abstinence at the end of treatment, and it probably increases adverse effects.

Emerging adulthood (EA) is a developmental period marked by unique challenges that affect health including burgeoning occupational, relational, and financial stability; and increased risk taking in terms of sexual behavior(s) and substance use. Data were collected from 296 HIV-uninfected sexual minority men with childhood sexual abuse (CSA) histories. We analyzed baseline assessment data from a multisite randomized controlled trial that tested the efficaciousness of an experimental psychosocial treatment and examined vulnerabilities known to be linked with CSA. Our analyses compared EA sexual minority men, aged 18-29, with older sexual minority men (OSMM) on posttraumatic stress disorder (PTSD) and other mental health and substance use outcomes. We found higher odds of PTSD, odds ratio (OR) = 0.57, 95% CI [0.33, 0.96]; panic disorder or panic disorder with agoraphobia, OR = 0.36, 95% CI [0.16, 0.85]; and cocaine use, OR = 0.50, 95% CI [0.25, 0.97], among OSMM and higher odds of alcohol intoxication, OR = 5.60, 95% CI [3.20, 9.82]; cannabis use, OR = 3.09, 95% CI [1.83, 5.21]; and non-HIV sexually transmitted infections, OR = 3.03, 95% CI [1.29, 7.13], among the EA men. These results present a complex picture of health risks among sexual minority men in general and EA sexual minority men in particular. HIV seroconversion linked health risk behaviors, among sexual minority men, may be better addressed via increased attention to treating trauma and comorbid mental health and substance use problems using evidence-based psychosocial assessments and integrated treatment platforms that are tailored to this population.

Click here to listen to the Podcast The one-third of people who do not gain seizure control through current treatment options need a revolution in epilepsy therapeutics. The general population appears to be showing a fundamental and rapid shift in its opinion regarding cannabis and cannabis-related drugs. It is quite possible that cannabidiol, licensed in the USA for treating rare genetic epilepsies, may open the door for the widespread legalisation of recreational cannabis. It is important that neurologists understand the difference between artisanal cannabidiol products available legally on the high street and the cannabidiol medications that have strong trial evidence. In the UK in 2018 there are multiple high-profile reports of the response of children taking cannabis-derived medication, meaning that neurologists are commonly asked questions about these treatments in clinic. We address what an adult neurologist needs to know now, ahead of the likely licensing of Epidiolex in the UK in 2019.

Although lower brain volume has been routinely observed in individuals with substance dependence compared with nondependent control subjects, the brain regions exhibiting lower volume have not been consistent across studies. In addition, it is not clear whether a common set of regions are involved in substance dependence regardless of the substance used or whether some brain volume effects are substance specific. Resolution of these issues may contribute to the identification of clinically relevant imaging biomarkers. Using pooled data from 14 countries, the authors sought to identify general and substance-specific associations between dependence and regional brain volumes.Brain structure was examined in a mega-analysis of previously published data pooled from 23 laboratories, including 3,240 individuals, 2,140 of whom had substance dependence on one of five substances: alcohol, nicotine, cocaine, methamphetamine, or cannabis. Subcortical volume and cortical thickness in regions defined by FreeSurfer were compared with nondependent control subjects when all sampled substance categories were combined, as well as separately, while controlling for age, sex, imaging site, and total intracranial volume. Because of extensive associations with alcohol dependence, a secondary contrast was also performed for dependence on all substances except alcohol. An optimized split-half strategy was used to assess the reliability of the findings.Lower volume or thickness was observed in many brain regions in individuals with substance dependence. The greatest effects were associated with alcohol use disorder. A set of affected regions related to dependence in general, regardless of the substance, included the insula and the medial orbitofrontal cortex. Furthermore, a support vector machine multivariate classification of regional brain volumes successfully classified individuals with substance dependence on alcohol or nicotine relative to nondependent control subjects.The results indicate that dependence on a range of different substances shares a common neural substrate and that differential patterns of regional volume could serve as useful biomarkers of dependence on alcohol and nicotine.

Recent increases in marijuana use among adolescents, in concert with decreases in perceptions of harm caused by marijuana use, documented associations of marijuana use with health problems and academic disengagement, and the increase in cannabis potency over the past two decades highlight the need for effective prevention and intervention efforts to delay and/or curb marijuana use among adolescents. The present study investigated the role of four promotive factors in the role of abstinence from marijuana use initiation.Low-income, urban, African American youth (N = 302; 54.6% female; M age = 12.05 years, SD = 1.57 years, Range = 10 to 16) participating in a larger study of stress and coping who had not initiated marijuana use at baseline were included in the sample. Goal directedness, emotion regulation, perceived support from mother, and religious coping, assessed at baseline, were evaluated for their contributions to marijuana use initiation two years later."By time 3, 14.7% of the sample reported having initiated marijuana use. Univariate analyses indicated that abstainers were younger, better able to regulate their emotions, and marginally more likely to use religious coping. Logistic regression analysis was used to develop a best-fitting model describing abstinence from marijuana use; this model revealed age and emotion regulation as unique contributors to abstinence.Emotion regulation is a teachable skill, and is included in many school-based prevention and parenting programs. Recommendations to enhance the effectiveness of self-regulation interventions in African American youth are discussed.

Prior research shows that cannabis use during treatment for Alcohol Use Disorders (AUD) is related to fewer abstinent days from alcohol, although only among those who use cannabis 1-2x/month. Here we extend prior research by assessing the relationship between the frequency of cannabis use during AUD treatment and post-treatment alcohol-related consequences.Data come from the Combined Pharmacotherapies and Behavioral Interventions (COMBINE) Study, a large US randomized control trial of treatments for AUD. The current analyses include 206 cannabis users and 999 cannabis abstainers and compare longitudinal drinking data between those who used cannabis versus those who abstained during COMBINE treatment. The primary exposure was quartiles of cannabis use (Q1: less than 1x/month during treatment, Q2: 1-2x/month, Q3: 4-8x/month, Q4: 12x/month or more), with cannabis abstainers as the reference group. Outcomes were alcohol-related problems at the end of treatment and one-year post-treatment as measured by the Drinker Inventory Consequences.Compared to cannabis abstinence, the most frequent use during treatment was related to 1.44 times as many physical consequences one-year post-treatment. Cannabis use was not related to physical consequences immediately after treatment, or to intrapersonal, interpersonal, social responsibility or impulse control problems at either post-treatment time point.In a sample of individuals in treatment for AUD, using cannabis 12x/month or more during treatment is associated with increased rates of physical consequences attributed to alcohol use. Individuals in treatment for AUD who also use cannabis might benefit from reducing or stopping cannabis use to avoid alcohol-related physical problems.

Normalisation of medicinal and recreational marijuana use has increased the importance of fully understanding effects of marijuana use on individual-and population-level health, including prenatal exposure effects on child development. We undertook a systematic review of the literature to examine the long-term effects of prenatal marijuana exposure on neuropsychological function in children aged 1-11 years.Primary research publications were searched from Medline, Embase, PsychInfo, CINAHL EbscoHost, Cochrane Library, Global Health and ERIC (1980-2018). Eligible articles documented neuropsychological outcomes in children 1-11 years who had been prenatally exposed to marijuana. Studies of exposure to multiple prenatal drugs were included if results for marijuana exposure were reported separately from other substances. Data abstraction was independently performed by two reviewers using a standardised protocol.The eligible articles (n = 21) on data from seven independent longitudinal studies had high quality based on the Newcastle-Ottawa Scale. Some analyses found associations (P < 0.05) between prenatal marijuana exposure and decreased performance on memory, impulse control, problem-solving, quantitative reasoning, verbal development and visual analysis tests; as well as increased performance on attention and global motion perception tests. Limitations included concurrent use of other substances among study participants, potential under-reporting and publication biases, non-generalisable samples and limited published results preventing direct comparison of analyses.The specific effects of prenatal marijuana exposure remain unclear and warrant further research. The larger number of neuropsychological domains that exhibit decreased versus increased psychological and behavioural functions suggests that exposure to marijuana may be harmful for brain development and function.

Background In those countries where cannabis use is still illegal, some manufacturers started producing and selling "light cannabis": dried flowering tops containing the psychoactive principle Δ-9-tetrahydrocannabinol (THC) at concentrations lower than 0.2% together with variable concentration of cannabidiol (CBD). We here report a pilot study on the determination of cannabinoids in the oral fluid and urine of six individuals after smoking 1 g of "light cannabis". Methods On site screening for oral fluid samples was performed, as a laboratory immunoassay test for urine samples. A validated gas chromatography-mass spectrometry (GC-MS) method was then applied to quantify THC and CBD, independently from results of screening tests. Results On site screening for oral fluid samples, with a THC cut-off of 25 ng/mL gave negative results for all the individuals at different times after smoking. Similarly, negative results for urine samples screening from all the individuals were obtained. Confirmation analyses showed that oral fluid THC was in the concentration range from 2.5 to 21.5 ng/mL in the first 30 min after smoking and then values slowly decreased. CBD values were usually one order of magnitude higher than those of THC. THC-COOH, the principal urinary THC metabolite, presented the maximum urinary value of 1.8 ng/mL, while urinary CBD had a value of 15.1 ng/mL. Conclusions Consumers of a single 1 g dose of "light cannabis" did not result as positive in urine screening, assessing recent consumption, so that confirmation would not be required. Conversely, they might result as positive to oral fluid testing with some on-site kits, with THC cut-off lower than 25 ng/mL, at least in the first hour after smoking and hence confirmation analysis can be then required. No conclusions can be drawn of eventual chronic users.

Cannabidiol (CBD), one of the non-psychotomimetic compounds of Cannabis sativa, causes anxiolytic-like effects in animals, with typical bell-shaped dose-response curves. No study, however, has investigated whether increasing doses of this drug would also cause similar curves in humans. The objective of this study was to compare the acute effects of different doses of CBD and placebo in healthy volunteers performing a simulated public speaking test (SPST), a well-tested anxiety-inducing method.A total of 57 healthy male subjects were allocated to receive oral CBD at doses of 150 mg (n=15), 300 mg (n=15), 600 mg (n=12) or placebo (n=15) in a double-blind procedure. During the SPST, subjective ratings on the Visual Analogue Mood Scale (VAMS) and physiological measures (systolic and diastolic blood pressure, heart rate) were obtained at six different time points.Compared to placebo, pretreatment with 300 mg of CBD significantly reduced anxiety during the speech. No significant differences in VAMS scores were observed between groups receiving CBD 150 mg, 600 mg and placebo.Our findings confirm the anxiolytic-like properties of CBD and are consonant with results of animal studies describing bell-shaped dose-response curves. Optimal therapeutic doses of CBD should be rigorously determined so that research findings can be adequately translated into clinical practice.

The present article is a synthesis of the first 10 years of follow-up of the FondaMental Academic Center of Expertise for Schizophrenia (FACE-SZ) cohort.More than 700 community-dwelling stabilized subjects have been recruited and evaluated to date. The mean age was 32 years with 75 % males, the mean illness duration was 11 years, the mean age at illness onset was 21 years, the mean duration of untreated psychosis was 1.5 years and 55 % were current daily tobacco smokers.The major findings of the FACE-SZ cohort may be summarized as follows: the metabolic syndrome is twice more frequent in schizophrenia as compared to the general population and is not correctly assessed and treated; cognitive disturbances have been found in benzodiazepine consumers and in patients with chronic low-grade peripheral inflammation; major depressive disorder (MDD) is a common current comorbid condition in about 20% of the subjects at the evaluation. MDD is associated with impaired quality of life and with increased nicotine dependency in SZ daily tobacco smokers. Improving depression and negative symptoms may be the most effective strategies to improve quality of life in schizophrenia; the duration of untreated psychosis is much longer in cannabis smokers and in subjects with an age at illness onset<19 years. Adherence to treatment is diminished in subjects who report a subjective negative feeling after treatment intake independent of objective side effects (extrapyramidal syndrome and weight gain). Akathisia has been found in 18% of the subjects and has been associated with antipsychotic polytherapy.In the light of these results, some recommendations for clinical care may be suggested. The early detection of schizophrenia should be specifically increased in adolescents and/or cannabis smokers. All patients should be administered a comprehensive neuropsychological evaluation at the beginning of the illness and after stabilization under treatment. Improving metabolic parameters and lifestyle (diet and physical activity) should be reinforced. The benefit/risk ratio of benzodiazepine and antipsychotic polytherapy should be regularly reevaluated and withdrawn as soon as possible. If MDD remains underdiagnosed and undertreated, improving depression may strongly improve the quality of life of SZ subjects. In the end, Cognitive Remediation Therapy and anti-inflammatory strategies should be more frequently included in therapeutic strategies.

There is an increased interest among patients with bipolar disorder for using medical cannabis. The aim of this review was to elucidate, whether medical cannabis has a potential role in the treatment of bipolar disorder. Only one study with two case reports has been conducted. The two manic patients showed no improvement during the treatment but tolerated cannabis, and no side effects were reported. Overall, there is a lack of evidence for the use of cannabis in bipolar disorder. Future randomised clinical trials are warranted.

Until recently, lung transplantation was not considered in patients with human immunodeficiency virus (HIV). HIV seropositive patients with suppressed viral loads can now expect long-term survival with the advent of highly active antiretroviral therapies (HAART); however, HIV remains a relative contraindication to lung transplantation. We describe, to our knowledge, the first HIV seropositive lung transplant recipient in Canada. We also review the literature of previously reported cases of solid-organ transplantation in patients with HIV with a focus on immunosuppression considerations.A 48-year old man received a bilateral lung transplant for a diagnosis of desquamative interstitial pneumonia (DIP) attributed to cigarette and cannabis smoking. His control of HIV infection pre-transplant was excellent on HAART, and he had no other contraindications to lung transplantation. The patient underwent bilateral lung transplantation using basiliximab, methylprednisolone, and mycophenolate mofetil (MMF) as induction immunosuppression. He was maintained on MMF, prednisone, and tacrolimus thereafter, and restarted his HAART regimen immediately post-operatively. His post-transplant course was complicated by Grade A1 minimal acute cellular rejection, as well as an enterovirus/rhinovirus graft infection. Despite these complications, his functional status and control of HIV infection remain excellent 24 months post-transplant.Our patient is one of only several HIV seropositive lung transplant recipients reported globally. With growing acceptance of transplantation in this population, there is a need for clarification of prognosis post-transplantation, as well as optimal immunosuppression regimens for these patients. This case report adds to the recent literature that suggests HIV seropositivity should not be considered a contraindication to lung transplantation, and that post-transplant patients with HIV can be managed safely with basiliximab, tacrolimus, MMF and prednisone.

Delta-9-tetrahydrocannabinol (THC), the main psychoactive cannabinoid in cannabis, may inhibit the cytochrome P450 enzyme CYP2C9. Consequently, cannabis use might infer a risk of drug-drug interaction with substrates for this enzyme, which includes drugs known to have a narrow therapeutic window. In this study, we describe a case report of a 27-year-old man treated with warfarin due to mechanical heart valve replacement who presented with elevated international normalized ratio (INR) value (INR = 4.6) following recreational cannabis use. We conducted a review of the available literature, using the PubMed and EMBASE databases while following PRISMA guidelines. Following screening of 85 articles, three eligible articles were identified, including one in vitro study and two case reports. The in vitro study indicated that THC inhibits the CYP2C9-mediated metabolism of warfarin. One case study reported of a man who on two occasions of increased marijuana use experienced INR values above 10 as well as bleeding. The other case study reported of a patient who initiated treatment with a liquid formulation of cannabidiol for the management of epilepsy, ultimately necessitating a 30% reduction in warfarin dose to maintain therapeutic INR values. The available, although sparse, data suggest that use of cannabinoids increases INR values in patients receiving warfarin. Until further data are available, we suggest patients receiving warfarin be warned against cannabis use.

Cardiovascular diseases are common co morbidities of schizophrenia and constitute the main factors of high mortality in this pathology. Cardiovascular damages are favored by some risk factors, of which one of the most important is dyslipidemia. In this context, a study of lipid profile in schizophrenia is interesting.  The aims of this study were to compare the lipid profile of patients with schizophrenia to healthy controls and to investigate the associations between lipid parameters and demographics, clinical and treatment characteristics of the patients.We conducted a case-control study between April 2013 and March 2014 on 78 patients with schizophrenia and 68 healthy subjects who benefited from the dosage of four serum lipid parameters: total cholesterol (TC), triglycerides (TG), High-density lipoprotein Cholesterol (HDL-C) and Low-density lipoprotein cholesterol (LDL-C). For the socio-demographic and clinical assessments, we used an information sheet and the following psychometric scales: PANSS (Positive And Negative Syndrome Scale), CGI (Clinical Global Impressions), GAF (Global Assessment Functionning) and the Calgary scale for depression.The comparative study showed that serum concentrations of TC and LDL-C were significantly higher for patients compared to healthy controls respectively with (t=2,83 ; p=0,008) and             (t=9,35; p<0,001), the cholesterol ratio (TC / HDL-C) was also significantly higher for patients           (t=2,23; p=0,033). The patients had significantly higher prevalence of hypercholesterolemia              (OR = 2.96) and low density hyperlipoproteinemia (OR = 18.79). The analytical study in the population of patients showed that the age ≥35 year-old, male gender and alcohol consumption were associated with disturbances in lipid parameters. Cannabis consumption was associated with significantly lower concentrations in TG. Concerning clinical features, paranoid schizophrenia was associated with less dyslipidemia unlike the depressive dimension assessed by the Calgary scale. There was a negative correlation between plasmatic TG concentrations and doses of antipsychotics.The vast majority of the literature confirms that patients with schizophrenia are at greater risk of dyslipidemia. This high risk appears to be more important with the consumption of alcohol and tobacco. It seems also that age and masculine gender are dyslipidemia risk factors for schizophrenic patients. The paranoid type of schizophrenia and positive symptoms seem to be associated with less dyslipidemia while depressive symptoms worsen lipid parameters. It then follows that, clinical and regular monitoring of lipid profile, lifestyle recommendations (smoking cessation, exercise and balanced diet) and appropriate therapeutic choices could help reduce morbidity and mortality among patients with schizophrenia. A special focus should be accorded to patients with high negative and depression symptoms.

It is known that Cannabis in Brazil could either originate from Paraguay or be cultivated in Brazil. While consumer markets in the North and Northeast regions are maintained by national production, the rest of the country is supplied with Cannabis from Paraguay. However, the Brazilian Federal Police (BFP) has exponentially increased the seizure number of Cannabis seeds sent by mail. For this reason, the aim of the study was to assess the 13-loci short tandem repeat (STR) multiplex system proposed by Houston et al. (2015) to evaluate the power of such markers in individualization and origin differentiation of Cannabis sativa samples seized in Brazil by the BFP. To do so, 72 Cannabis samples seized in Brazil by BFP were analyzed. The principal coordinate analysis (PCoA) and probability identity (PI) analysis were computed. Additionally, the Cannabis samples' genotypes were subjected to comparison by Kruskal-Wallis H, followed by a multiple discriminant analysis (MDA). All samples analyzed revealed a distinct genetic profile. PCoA clearly discriminated the seizure sets based on their geographic origin. A combination of seven loci was enough to differentiate samples' genotypes, and the PI for a random sample is approximately one in 50 billion. The Cannabis samples were 100% correct as classified by Kruskal-Wallis H, followed by an MDA. The results of this study demonstrate that the 13-loci STR multiplex system successfully achieved the aim of sample individualization and origin differentiation and suggest that it could be a useful tool to help BFP intelligence in tracing back-trade routes.

Custody conditions in police cells are often demeaning and considered inappropriate for human beings. The detention of young adolescents in police custody has received little attention. Our study aimed to describe the characteristics of adolescents under 18 detained in custody.We studied all arrestees aged 13-17 examined in 1 year (January 01-December 31, 2014) in a suburban district near Paris. We evaluated the proportion of adolescents under 18 among all arrestees detained in custody and their medical history, addictive behaviors, perceived health status, and opinion on custody.Arrestees aged 13-17 accounted for 1859 individuals. They were predominantly males (94%) and accounted for 19% of all examinations in custody. Nearly half of the arrestees aged 13-15 (42%), and two thirds of those aged 16-17 (65%) had been previously detained in police cells. Somatic and psychiatric disorders were reported by 7% and 4%, respectively, of arrestees aged 13-17. Alcohol, tobacco, and cannabis consumption were reported by 5%, 24%, and 12%, respectively, of arrestees aged 13-15. These proportions were lower than the 16%, 50%, and 35%, respectively, reported by arrestees aged 16-17 (p < 0.0001). Assaults were reported by 18% of arrestees aged 13-17. They had a fair, bad, or very bad opinion on custody in 43% of cases.The detention of adolescents in police stations is commonly associated with assaults at the time of arrest. High proportions of adolescent arrestees smoke tobacco or cannabis. We suggest that the medical examination in custody could be an opportunity for adolescents to initiate access to health care.

Introduction: Long-term consequences of medicinal cannabis use in people with multiple sclerosis (PwMS) are unknown. This study investigated whether PwMS using cannabis had lower resting brain glucose uptake (GU) and worse clinical test results compared with nonusers. Methods: Sixteen PwMS, eight users, underwent clinical testing followed by [18F]-Fluorodeoxyglucose positron emission tomography/computed tomography imaging. Results: Users had lower cognitive function test scores, but performed similarly on the other clinical evaluations. Accounting for disease duration, resting brain GU was similar between the groups. Conclusions: Lower cognitive function was not associated with resting brain GU. Cognitive dysfunction may be a contraindication or consequence of cannabis use in PwMS.

We present the case of a 33-year-old male who presented to the Emergency Department having amputated his penis as a result of auditory hallucinations triggered by cannabis use. A successful microsurgical technique involving anastomosing the individual structures of the penile shaft enabled a successful cosmetic and functional outcome including restoration of erectile function.

A young woman with chronic cannabis use presents with 2-day history of cyclical nausea, vomiting and abdominal pain. Clinical and laboratory examination excluded other causes. Patient's symptoms improved with topical capsaicin, hot showers, antiemetics and she was subsequently discharged home 4 days later. The patient was educated on side effects of cannabis use and chose to stop cannabis use completely.

With the legalization of cannabis in Canada, young adults, who are already at risk of automobile crashes, may increase their use of cannabis, which may further increase the risk of crashes. We examined the effects of inhaled cannabis on driving-related performance in healthy 18- to 24-year-old recreational cannabis users.In this within-subject randomized study, participants completed tests in the no-cannabis state and at 1, 3 and 5 hours after inhalation of a standard 100-mg dose of cannabis. We then measured performance (in useful-field-of-view and driving-simulation tests) and self-reported perceptions (driving ability and safety, cannabis effects). Repeated-measures analysis of variance (for cannabis effects on continuous performance measures), Cochran Q tests (for performance-related crash risk and binary complex simulator task scores) and correlational analyses (for self-reported perceptions relative to performance) were employed.Forty-five participants completed all 180 testing sessions. Significant effects of cannabis (relative to no cannabis) were noted on complex useful-field-of-view tasks at 3 hours (complex divided-attention task: 70 ± 24 ms v. 37 ± 12 ms, 95% confidence intervals [CIs] 28-114 ms v. 29-45 ms, t = -2.98, df = 41, p = 0.005; complex selective-attention task: 102 ± 66 ms v. 64 ± 18 ms, 95% CIs 60-144 ms v. 53-75 ms, t = -2.42, df = 41, p = 0.02) and 5 hours (complex selective-attention task: 82 ± 29 ms v. 61 ± 19 ms, 95% CIs 62-100 ms v. 48-75 ms, t = -2.32, df = 41, p = 0.03) after cannabis use when the tasks were novel (performed in a cannabis state at the first session). Participants were significantly more likely to be classified as having a high crash risk (on the basis of simulator tasks) after cannabis use (χ 2 = 13.23, df = 1, p < 0.001, odds ratio 4.31, 95% CI 0.41-45.2) and reported significantly lower perceived driving ability and safety after cannabis use relative to non-use.Among young recreational cannabis users, a 100-mg dose of cannabis by inhalation had no effect on simple driving-related tasks, but there was significant impairment on complex tasks, especially when these were novel. These effects, along with lower self-perceived driving ability and safety, lasted up to 5 hours after use.The trial was registered with Health Canada (NOL [No Objection Letter] no. 215101).

Cannabis sativa L. is a dioecious plant belonging to the Cannabaceae family. The main phytochemicals that are found in this plant are represented by cannabinoids, flavones, and terpenes. Some biological activities of cannabinoids are known to be enhanced by the presence of terpenes and flavonoids in the extracts, due to a synergistic action. In the light of all the above, the present study was aimed at the multi-component analysis of the bioactive compounds present in fibre-type C. sativa (hemp) inflorescences of different varieties by means of innovative HPLC and GC methods. In particular, the profiling of non-psychoactive cannabinoids was carried out by means of HPLC-UV/DAD, ESI-MS, and MS². The content of prenylated flavones in hemp extracts, including cannflavins A and B, was also evaluated by HPLC. The study on Cannabis volatile compounds was performed by developing a new method based on headspace solid-phase microextraction (HS-SPME) coupled with GC-MS and GC-FID. Cannabidiolic acid (CBDA) and cannabidiol (CBD) were found to be the most abundant cannabinoids in the hemp samples analysed, while β-myrcene and β-caryophyllene were the major terpenes. As regards flavonoids, cannflavin A was observed to be the main compound in almost all the samples. The methods developed in this work are suitable for the comprehensive chemical analysis of both hemp plant material and related pharmaceutical or nutraceutical products in order to ensure their quality, efficacy, and safety.

Both cannabis use and alcohol use are elevated among people living with HIV, but few studies have investigated the relationship between cannabis use and alcohol use in this population. This study examined the longitudinal association between cannabis use and alcohol use among people living with HIV and explored the moderating role of medicinal vs. recreational cannabis use.Participants were cannabis users (N=763) enrolled in the Ontario HIV Treatment Network Cohort Study (67% White, 88% male, 68% gay, median income in the $40,000-$50,000 range). Participants completed assessments of cannabis use, reasons for cannabis use, and alcohol use at baseline and at annual follow-ups (M = 3.42 completed assessments). Multilevel modeling was used to examine between-person and within-person associations between cannabis use and alcohol use over time.Greater average frequency of cannabis use was associated with greater average alcohol consumption across participants. Participants classified as medicinal cannabis users reported more frequent cannabis use and less alcohol use on average than recreational cannabis users. Further, within-person changes in cannabis use over time were positively associated with corresponding changes in alcohol use for recreational cannabis users but not for medicinal users.Cannabis use and alcohol use were positively associated over time among people living with HIV, although this association was specific to those using cannabis for recreational reasons. As alcohol use in this population poses significant health risks, more research on the link between cannabis use and alcohol use is needed, particularly in light of recent changes to cannabis regulations.

The objective of the study was to examine if depression or anxiety was associated with youth cannabis use; and investigate whether flourishing, an indicator of overall wellbeing, moderates these associations.Students (N=6550) were recruited from 10 secondary schools (grade 9-12) in Ontario and British Columbia, Canada. Self-report questionnaires were used to assess symptoms of depression [CESD-R-10], anxiety [GAD-7], flourishing [Deiner's Flourishing Scale], and cannabis use. Logistic regression and product-term interactions were used to examine the associations between mental health and youth cannabis use, and the potential moderating effect(s) of flourishing.In our sample, 32% of participants had ever used cannabis, and 42% and 32% reported elevated depressive and anxiety symptoms, respectively. Associations between depression, anxiety, and cannabis use were no longer significant when flourishing was added to the models. In addition, there was no evidence suggesting a moderating effect of flourishing (all interactions were not statistically significant). Instead, robust associations were found between flourishing and cannabis use (ever use and frequency).Indicators of mental wellbeing, such as flourishing, appear to be associated with a lower likelihood of cannabis use, even after controlling for depression and anxiety. Results suggest prevention strategies for youth cannabis use should aim to foster mental wellbeing among all youth, rather than exclusively targeting those experiencing mental health problems. Future longitudinal studies should test the sequential relationship between cannabis use and changes in both positive and negative mental health.

Cannabis is used worldwide. So, it is necessary to stay especially concerned by the medical and social consequences of its use. For a long time, it was seen as a " soft drug ", in reference to the apparent low medical risk related to its use. However, the psycho-social consequences of cannabis use albeit of major importance are commonly neglected. Furthermore, danger for the health does exist, both from psychiatry and somatic medicine points of view. The danger is growing especially due to the apparition on the market of more potent presentations of cannabinoids.

Mescaline (3,4,5-trimethoxyphenethylamine), mainly found in the Peyote cactus (Lophophora williamsii), is one of the oldest known hallucinogenic agents that influence human and animal behavior, but its psychoactive mechanisms remain poorly understood.This article aims to fully review pharmacokinetics and pharmacodynamics of mescaline, focusing on the in vivo and in vitro metabolic profile of the drug and its implications for the variability of response.Mescaline pharmacokinetic and pharmacodynamic aspects were searched in books and in PubMed (U.S. National Library of Medicine) without a limiting period. Biological effects of other compounds found in peyote were also reviewed.Although its illicit administration is less common, in comparison with cocaine and Cannabis, it has been extensively described in adolescents and young adults, and licit consumption often occurs in religious and therapeutic rituals practiced by the Native American Church. Its pharmacodynamic mechanisms of action are primarily attributed to the interaction with the serotonergic 5-HT2A-C receptors, and therefore clinical effects are similar to those elicited by other psychoactive substances, such as lysergic acid diethylamide (LSD) and psilocybin, which include euphoria, hallucinations, depersonalization and psychoses. Moreover, as a phenethylamine derivative, signs and symptoms are consistent with a sympathomimetic effect. Mescaline is mainly metabolized into trimethoxyphenylacetic acid by oxidative deamination but several minor metabolites with possible clinical and forensic repercussions have also been reported.Most reports concerning mescaline were described in a complete absence of exposure confirmation, since toxicological analysis is not widely available. Addiction and dependence are practically absent and it is clear that most intoxications appear to be mild and are unlikely to produce life-threatening symptoms, which favors the contemporary interest in the therapeutic potential of the drugs of the class.

As an increasing number of states begin to legalize marijuana for either medical or recreational use, it is important to determine its effects on joint arthroplasty. The purpose of this study is to determine the impact of cannabis use on total knee arthroplasty (TKA) revision incidence, revision causes, and time to revision by analyzing the Medicare database between 2005 and 2014. A retrospective review of the Medicare database for TKA, revision TKA, and causes was performed utilizing Current Procedural Terminology (CPT) and International Classification of Disease ninth revision codes (ICD-9). Patients who underwent TKA were cross-referenced for a history of cannabis use by querying ICD-9 codes 304.30-32 and 305.20-22. The resulting group was then longitudinally tracked postoperatively for revision TKA. Cause for revision, time to revision, and gender were also investigated. Our analysis returned 2,718,023 TKAs and 247,112 (9.1%) revisions between 2005 and 2014. Cannabis use was prevalent in 18,875 (0.7%) of TKA patients with 2,419 (12.8%) revisions within the cannabis cohort. Revision incidence was significantly greater in patients who use cannabis (p < 0.001). Time to revision was also significantly decreased in patients who used cannabis, with increased 30- and 90-day revision incidence compared to the noncannabis group (P < 0.001). Infection was the most common cause of revision in both groups (33.5% nonusers versus 36.6% cannabis users).Cannabis use may result in decreasing implant survivorship and increasing the risk for revision within the 90-day global period compared to noncannabis users following primary TKA.

There is growing interest in non-invasive brain stimulation techniques as treatments for addictive disorders. While multiple reviews have examined the effects of neuromodulation on craving and consumption, there has been no review of how neuromodulation affects cognitive functioning in addiction. This systematic review examined studies of the cognitive effects of transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS) in individuals exhibiting addictive behavior.Articles were identified through searches in PubMed and PsycINFO conducted in October 2017. Eligible studies investigated the effects of tDCS or TMS on cognitive task performance in participants reporting substance use (e.g., alcohol, tobacco, or drugs) or addictive behaviors (e.g., gambling). Tasks were organized into five domains: (1) Inhibitory control, (2) Risk-taking, (3) Impulsive choice (delay discounting), (4) Executive function, and (5) Implicit biases.Twenty-four articles met the inclusion criteria. Fifty-seven percent of studies used tDCS and 43% used TMS, with nearly all studies (96%) targeting the dorsolateral prefrontal cortex. Ten studies reported significant within-subject modulation of cognitive functioning associated with active TMS or tDCS, with the same number reporting no change in cognitive performance. Of four studies that included both an experimental and control participant group, three showed between-group differences in the effects of neuromodulation.While positive effects in several studies suggest that tDCS and TMS improve cognitive functioning in addiction, there is substantial heterogeneity across studies. We discuss person-related and methodological factors that could explain inconsistencies, and propose individualized stimulation protocols may sharpen the cognitive effects of neuromodulation in addiction.

Medical cannabis is becoming increasingly popular for many different ailments and improvement of general well-being. Particularly CBD-rich extracts are easily available via online pharmacies, health stores or directly from producers. However, almost all of the extracts contain small amounts of THC. Thus, in case of continuous or heavy use of CBD rich cannabis, THC concentrations in hair may rise above accepted legal limits. In our study, we investigated THC, CBN and CBD in hair samples from regular CBD rich cannabis users. The goals were to determine levels of the cannabinoids in hair and to evaluate a possible correlation between regular CBD intake and CBD levels in hair. All participants consumed cannabis extracts from the same producer. It contained CBD at different concentrations and small amounts of THC with a CBD/THC concentration ratio of 30. The self-declared CBD dosage ranged from 4 to 128mg CBD/day, corresponding to a daily THC intake of 0.1 to 4.3mg. After extraction and derivatization, hair samples were analysed using a validated GC/MS-MS method. CBD concentrations ranged from 10 to 325pg/mg of hair, but no significant correlation was observed between CBD concentrations and the daily dose. THC was detected in one sample only at a concentration below our cut-off, whereas CBN was not detected. In this study, we showed that even after repeated consumption of CBD-rich cannabis extracts in medium to high doses, consumers are generally tested negative for THC in hair.

Cannabis is the most commonly used illicit substance among Canadian youth. The current study examined national trends in cannabis use among Canadian youth from 2004/05 to 2014/15 using nationally representative data from the Canadian Student Tobacco, Alcohol and Drugs Survey (CSTADS). Data were collected from students in Grades 7 to 12 as part of the Canadian Student Tobacco, Alcohol and Drugs Survey (formerly the Youth Smoking Survey) using a repeat-cross sectional survey across 6 biennial survey waves between 2004 and 2014 (N = 243,057). Regression models examined factors associated with cannabis use in the past 12 months, perceived ease of access, and a multilinear regression examined age of initiation across survey cycles. The findings indicate that use of cannabis in the past 12-months significantly decreased among Canadian youth. Past-year use peaked in 2008/09 at 27.3%; compared to 16.5%, in 2014/15. Mean age of initiation did not vary over time, while youth in recent cycles reported that cannabis was more difficult to access: in 2006/07, 77.1% reported that it would be easy to access cannabis compared to 49.0% in 2014/15. Overall, cannabis use among Canadian youth appears to have peaked around 2008/09, with substantial declines over the past decade. It will be critically important to examine any changes in patterns of use following legalization of non-medical cannabis in Canada.

Clinical studies have shown that the major psychoactive ingredient of Cannabis sativa Δ9-tetrahydrocannabinol (THC) has some analgesic efficacy in neuropathic pain states. However, THC has a significant side effect profile. We examined whether the profile of THC could be improved by co-administering it with the first-line neuropathic pain medication gabapentin. This was done using the chronic constriction injury (CCI) model of neuropathic pain in C57BL6 mice. At 8 days post-CCI nerve injury, acute systemic administration of gabapentin produced a dose-dependent decrease in CCI-induced mechanical and cold allodynia, and increased motor incoordination. Coadministration of THC and gabapentin in a fixed-ratio dose-dependently reduced mechanical and cold allodynia, and produced all the side-effects observed for THC, including motor incoordination, catalepsy and sedation. Isobolographic analysis indicated that the ED50 for the THC:gabapentin induced reduction in allodynia was 1.7 times less than that predicted for an additive interaction. The therapeutic window of combination THC:gabapentin was greater than that for THC alone. These findings indicate that gabapentin synergistically enhances the anti-allodynic actions of THC and improves its therapeutic window. Thus, THC may represent a potential adjuvant for neuropathic pain medications such as gabapentin.

Early intervention psychiatric services for patients with psychosis aim to limit the most damaging outcomes and reduce the patient's risk of social drift, decreasing illness severity and thus containing healthcare costs. There is a scarcity of studies that focus on first-episode psychosis (FEP), and those few that have been published only looked at direct health costs, but not at indirect costs, which make up the bulk of the budget. Our study aims to explore the short-term (1-year follow-up) economic cost of a FEP Program, including both direct and indirect costs.Data were collected retrospectively from the clinical records of 157 patients included in the Programa Atención Fases Iniciales de Psicosis, from Marqués de Valdecilla University Hospital, Santander. Our data collection sheet collated data from direct and indirect costs associated with the illness. Data were also extracted from the Cantabria Health Service Records. STATA 15.0 was used for statistical analysis.On average, the total costs during the first year were €48 353.51 per patient, with direct healthcare costs being €13 729.47 (28.39%), direct non-medical costs €108.6 (0.22%), and indirect costs €34 515.44 (71.39%). We found that hospitalization costs were higher in males (p = 0.081) and in cannabis users (p = 0.032). The number of relapses increased both, hospitalization and treatment costs (r = 0.40 p = 0.000; r = 0.24 p = 0.067, respectively).Intensive Early Intervention in Psychosis Services may result in cost savings by decreasing hospitalization, premature mortality, disability, unemployment, and legal problems; however, the first year after diagnosis would represent the one with the highest costs.

A priori power analysis is increasingly being recognized as a useful tool for designing efficient research studies that improve the probability of robust and publishable results. However, power analyses for many empirical designs in the addiction sciences require consideration of numerous parameters. Identifying appropriate parameter estimates is challenging due to multiple sources of uncertainty, which can limit power analyses' utility.We demonstrate a sensitivity analysis approach for systematically investigating the impact of various model parameters on power. We illustrate this approach using three design aspects of importance for substance use researchers conducting longitudinal studies base rates, individual differences (i.e., random slopes), and correlated predictors (e.g., co-use) and examine how sensitivity analyses can illuminate strategies for controlling power vulnerabilities in such parameters.Even large numbers of participants and/or repeated assessments can be insufficient to observe associations when substance use base rates are too low or too high. Large individual differences can adversely affect power, even with increased assessments. Collinear predictors are rarely detrimental unless the correlation is high.Increasing participants is usually more effective at buffering power than increasing assessments. Research designs can often enhance power by assessing participants twice as frequently as substance use occurs. Heterogeneity should be carefully estimated or empirically controlled, whereas collinearity infrequently impacts power significantly. Sensitivity analyses can identify regions of model parameter spaces that are vulnerable to bad guesses or sampling variability. These insights can be used to design robust studies that make optimal use of limited resources.

Cannabis is often used by consumers for sleep disorders. Studies show that circadian rhythm could be affected by a misuse of cannabis. Recent research has connected the role of microglial cells with psychiatric disorders such as substance abuse. The aim was to show the effect of two major components of cannabis on circadian genes regulation in microglial cells. In BV-2 microglial cells, cannabidiol (CBD) induces a deregulation of circadian genes with (P-value = 0.039) or without (P-value = 0.0015) lipopolisaccharides stimulation. CBD up regulated Arntl (P = 9.72E-5) and down regulated Clock (P = 0.0034) in BV-2 cells. Temporal expression of Arntl (light and dark P = 0.0054) and Clock (light and dark P = 0.047) was confirmed to have 24 hours light and dark rhythmic regulation in dissected suprachiasmatic nucleus as well as of Cb1 cannabinoid receptor (light and dark P = 0.019). In BV-2 microglia cells, CBD also up regulated CRY2 (P = 0.0473) and PER1 (P = 0.0131). Other nuclear molecules show a deregulation of circadian rhythm in microglial cells by CBD, such as RORA, RevErbα, RORB, CREBBP, AFT4, AFT5 and NFIL3. Our study suggests that circadian rhythm in microglial cells is deregulated by CBD but not by THC. It is consistent with clinical observations of the use of therapeutic cannabis to treat insomnia.

Cannabinoid hyperemesis syndrome is a condition characterized by chronic cannabis use and cyclic episodes of nausea, vomiting, and abdominal pain, relieved by compulsive bathing. The syndrome is likely to be underdiagnosed in pregnant women due to its similarity with hyperemesis gravidarum in the presentation.We report a 20-year-old pregnant woman with multiple admissions for recurrent nausea and vomiting who was observed to be taking frequent hot showers. Without other identifiable causes, she was diagnosed with cannabinoid hyperemesis syndrome and managed with antiemetics and abstinence.Abstinence from cannabis use is highly recommended in pregnant women due to its potential harm in fetal development and stimulation of intractable nausea and vomiting. Recognizing the symptoms and proper history taking prompt early diagnosis, allowing timely and adequate treatment.

The use of psychoactive substances, including methamphetamine (MA) may cause changes in DNA methylation. The aim of this study was to examine the effects of MA use on long interspersed element-1 (LINE-1) methylation patterns in association with MA-induced paranoia. This study recruited 123 normal controls and 974 MA users, 302 with and 672 without MA-induced paranoia. The Semi-Structured Assessment for Drug Dependence and Alcoholism was used to assess demographic and substance use variables. Patterns of LINE-1 methylation were assessed in peripheral blood mononuclear cells and a combined bisulfite restriction analysis (COBRA) was used to estimate overall LINE-1 methylation (mC) while COBRA classified LINE-alleles into four patterns based on the methylation status of two CpG dinucleotides on each strand from 5' to 3', namely two methylated (mCmC) and two unmethylated (uCuC) CpGs and two types of partially methylated loci (mCuC that is 5'm with 3'u and uCmC that is 5'u with 3'm CpGs). MA users showed higher % mCuC and % mCuC + uCmC levels than controls. Use of solvents and opioids, but not cannabis and alcohol dependence, significantly lowered % uCmC levels, while current smoking significantly increased % uCuC levels. MA-induced paranoia was strongly associated with changes in LINE-1 partial methylation patterns (lowered % uCmC), heavy MA use, lower age at onset of MA use, and alcohol dependence. Women who took contraceptives showed significantly lower LINE-1 % mC and % mCmC and higher % uCuC levels than women without contraceptive use and men. The results show that MA-induced changes in LINE-1 partial methylation patterns are associated with MA-induced paranoia and could explain in part the pathophysiology of this type of psychosis. It is argued that MA-induced neuro-oxidative pathways may have altered LINE-1 partial methylation patterns, which in turn may regulate neuro-oxidative and immune pathways, which may increase risk to develop MA-induced paranoia.

Cannabis vaping and edible use are increasingly popular methods of cannabis use. These discreet methods could increase risk of cannabis-related problems by facilitating cannabis use in a wider range of settings.A sample of 1018 college students were recruited to complete a survey about their health and behavior. Participants who used cannabis in the past year (35.1%, n = 357) answered questions about their cannabis use, including where they were the last time they smoked, vaped, or ate/drank cannabis, and their experience of cannabis-related problems.Compared with cannabis smoking, participants were more likely to have vaped cannabis (15.8% smoked vs. 24.6% vaped; X2 = 4.59, p = .032), and were slightly, but not statistically significantly, more likely to have used cannabis edibles (17.5% smoked vs. 24.2% used edibles; X2 = 3.57, p = .059), in locations other than a private residence. For example, participants were more likely to have vaped cannabis in a car than to have smoked cannabis in a car (8.8% vaped vs. 3.5% smoked; X2 = 4.26, p = .039). More frequent cannabis vaping was associated with driving while high on cannabis, even after accounting for overall frequency of cannabis use and other covariates (OR = 1.22, p = .047). More frequent cannabis vaping and edible use were associated with various cannabis-related problems, but, in general, these associations became statistically non-significant after accounting for overall frequency of cannabis use.Cannabis vaporizers and edibles facilitate cannabis use in locations that require discretion. Increased availability of cannabis vaporizers and edibles could increase risk of cannabis-related problems by enabling use in more settings.

Age has been shown to have an impact on both grey (GM) and white matter (WM) volume, with a steeper slope of age-related decline in schizophrenia compared to healthy controls. In schizophrenia, the relation between age and brain volume is further complicated by factors such as lower intelligence, antipsychotic medication, and cannabis use, all of which have been shown to have independent effects on brain volume. In a study of first-episode, antipsychotic-naïve schizophrenia patients (N = 54) and healthy controls (N = 56), we examined the effects of age on whole brain measures of GM and WM volume, and whether these relationships were moderated by schizophrenia and intelligence (IQ). Secondarily, we examined lifetime cannabis use as a moderator of the relationship between age and brain volume. Schizophrenia patients had lower GM volumes than healthy controls but did not differ on WM volume. We found an age effect on GM indicating that increasing age was associated with lower GM volumes, which did not differ between groups. IQ did not have a direct effect on GM, but showed a trend-level interaction with age, suggesting a greater impact of age with lower IQ. There were no age effects on WM volume, but a direct effect of IQ, with higher IQ showing an association with larger WM volume. Lifetime cannabis use did not alter these findings significantly. This study points to effects of schizophrenia on GM early in the illness, before antipsychotic treatment is initiated, suggesting that WM changes may occur later in the disease process.

Missing data for the outcomes of participants in randomized controlled trials (RCTs) are a key element of risk of bias assessment. However, it is not always clear from RCT reports whether some categories of participants were followed-up or not (i.e., do or do not have missing data) nor how the RCT authors dealt with missing data in their analyses. Our objectives were to describe how RCT authors (1) report on different categories of participants that might have missing data, (2) handle these categories in the analysis, and (3) judge the risk of bias associated with missing data.We surveyed all RCT reports included in 100 clinical intervention systematic reviews (SRs), half of which were Cochrane SRs. Eligible SRs reported a group-level meta-analysis of a patient-important dichotomous efficacy outcome, with a statistically significant effect estimate. Eleven reviewers, working in pairs, independently extracted data from the primary RCT reports included in the SRs. We predefined 19 categories of participants that might have missing data. Then, we classified these participants as follows: "explicitly followed-up," "explicitly not followed-up" (i.e., definitely missing data), or "unclear follow-up status" (i.e., potentially missing data).Of 638 eligible RCTs, 400 (63%) reported on at least one of the predefined categories of participants that might have missing data. The median percentage of participants who were explicitly not followed-up was 5.8% (interquartile range 2.2-14.8%); it was 9.7% (4.1-14.9%) for participants with unclear follow up status; and 11.7% (interquartile range 5.6-23.7%) for participants who were explicitly not followed-up and with unclear follow-up status. When authors explicitly reported not following-up participants, they most often conducted complete case analysis (54%). Most RCTs neither reported on missing data separately for different outcomes (99%) nor reported using a method for judging risk of bias associated with missing data (95%)."Potentially missing data" are considerably more frequent than "definitely missing data." Adequate reporting of missing data will require development of explicit standards on which editors insist and to which RCT authors adhere.

Widespread use of cannabis as a drug and passage of legislation on its use should lead to an increase in the number of scientific publications on cannabis. The aim of this study was to compare trends in scientific publication for papers on medical cannabis, papers on cannabis in general, and all papers between the years 2000 and 2017. A search of PubMed and Web of Science was conducted. The overall number of scientific publications in PubMed increased 2.5-fold. In contrast, the number of publications on cannabis increased 4.5-fold and the number of publications on medical cannabis increased almost 9-fold. The number of publications on medical cannabis in Web of science increased even more (10-fold). The most significant number of publications was in the field of psychiatry. In the fields of neurology and cancer treatment there was a significant increase in the years 2011-2013. There was a rise in the number of publications on children and the elderly after 2013. The specific indications with the largest number of publications were HIV (261), chronic pain (179), multiple sclerosis (118), nausea and vomiting (102), and epilepsy (88). More than half of the publications on medical cannabis originated from the United States, followed by Canada. More than 66% of the publications were original studies. The spike in the number of scientific publications on medical cannabis since 2013 is encouraging. In light of this trend the authors expect an even greater increase in the number of publications in this area in coming years.

To assess Australian psychiatrists' and psychiatry trainees' knowledge about and attitudes towards medicinal cannabinoids, given the recent relaxation of cannabinoid-prescribing laws in Australia.All Australian members of the Royal Australian and New Zealand College of Psychiatrists were invited to participate in an anonymous, 64-item online questionnaire, through Royal Australian and New Zealand College of Psychiatrists' newsletters. The questionnaire ran for a 10-week period from March to May 2017. Participants were asked about their knowledge of the evidence for and against prescribing pharmaceutical-grade cannabidiol and tetrahydrocannabinol, and their concerns about prescribing medicinal cannabinoids.In total, 88 doctors responded to the survey, with 55 completing all items (23 psychiatrists, 32 trainees). Overall, 54% of respondents would prescribe medicinal cannabinoids if it was legal to do so. Participants believed there was evidence for the use of cannabidiol and tetrahydrocannabinol in treating childhood epilepsy, chronic pain, and nausea and vomiting. They were most concerned about medicinal cannabinoids leading to psychotic symptoms, addiction and dependence, apathy and recreational use.Our sample of Australian psychiatrists and trainees were aware of the main clinical indications for medicinal cannabinoids, but were poor at differentiating between the indications for cannabidiol versus tetrahydrocannabinol. Further education about medicinal cannabinoids appears necessary.

Among college students, interpersonal conflict with others is a common, yet stressful negative interpersonal experience. Research suggests that drinking episodes may contribute to the occurrence of conflict. Marijuana use, independently or in conjunction with alcohol, may also influence the likelihood of subsequent conflict.We considered the temporal effects of independent and simultaneous alcohol and marijuana use episodes on the occurrence of interpersonal conflict. Use of multilevel modeling allowed us to distinguish the within-person effects of substance use from between-person differences in frequency of use.Within a sample of 427 college freshman males over 56 days of daily reports, we examined the independent and interactive effects of episodes of alcohol and marijuana on the odds of conflict within the next 1-, 2-, 3-, and 4 hours.Multilevel modeling analyses showed that drinking episodes increased the likelihood of conflict occurring within the next 1, 2, 3, and 4 hours. Marijuana had weaker positive effects, significant only within the 2 hour window. There were no alcohol by marijuana interaction effects in any analysis.Both marijuana and alcohol independently increased the likelihood of interpersonal conflict; however, the marijuana effect appeared less robust. As marijuana use becomes more normative and accessible for college students, it is important to understand the extent to which marijuana use results in negative consequences and the contexts under which these effects unfold.

Background: Among the many cannabinoids in the cannabis plant, cannabidiol (CBD) is a compound that does not produce the typical subjective effects of marijuana. Objectives: The aim of the present review is to describe the main advances in the development of the experimental and clinical use of cannabidiol CBD in neuropsychiatry. Methods: A non-systematic search was performed for studies dealing with therapeutic applications of CBD, especially performed by Brazilian researchers. Results: CBD was shown to have anxiolytic, antipsychotic and neuroprotective properties. In addition, basic and clinical investigations on the effects of CBD have been carried out in the context of many other health conditions, including its potential use in epilepsy, substance abuse and dependence, schizophrenia, social phobia, post-traumatic stress, depression, bipolar disorder, sleep disorders, and Parkinson. Discussion: CBD is an useful and promising molecule that may help patients with a number of clinical conditions. Controlled clinical trials with different neuropsychiatric populations that are currently under investigation should bring important answers in the near future and support the translation of research findings to clinical settings.

Synthetic cannabinoid intoxication has become difficult to diagnose and manage in the United States, in part due to varying clinical effects within this heterogeneous group of compounds.A 38-year-old man was admitted with altered mental status and bradycardia. He demonstrated progressive encephalopathy, seizure activity, second-degree atrioventricular block type I, respiratory failure, hypotension, hypothermia, and hypoglycemia. A computed tomography scan of the abdomen and pelvis revealed multiple packages in the patient's stomach and rectum. Multiple attempts at gastrointestinal decontamination were unsuccessful. On hospital day 8 the patient developed hypertensive emergency and was taken to the operating room for exploratory laparotomy. Twenty-two poorly wrapped packages were removed from the bowel. Postoperatively the patient demonstrated both generalized and focal seizure activity. His mental status slowly returned to baseline over the period of about 1 week and he was ultimately discharged without neurological sequelae after 1 month. Analysis of patient serum, urine, and plant matter from the packages identified cannabis and 2.N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-(4-fluorobenzyl)-1H-indazole-3-carboxamide (ADB-FUBINACA). WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: The case presented demonstrates the suspected toxidrome associated with severe ADB-FUBINACA intoxication, including mental status depression, bradycardia, autonomic instability, seizure, hypoglycemia, and hypothermia. Although the patient had simultaneous exposure to cannabis, his constellation of symptoms is not consistent with cannabis intoxication. A previous animal model supports the potential of this specific synthetic cannabinoid to cause the reported toxidrome.

Nyaope, a street drug commonly found in South Africa, is a mixture of low grade heroin, cannabis products, antiretroviral drugs and other materials added as cutting agents. It is a highly physiologically addictive substance which is smoked by users. Little work has been published on the chemical analysis and profiling of nyaope. Sample preparation prior to chromatographic or spectrometric analysis normally involves dissolution of the sample in an organic solvent. This study determined the most suitable organic solvent in which the common components of nyaope, namely Δ9-tetrahydrocannabinol, diamorphine, caffeine, dextromethorphan, phenacetin and the antiretrovirals efavirenz and nevirapine, which have different chemical characteristics, are stable during extraction and prior to analysis of nyaope samples i.e. autosampler stability. Street samples of cannabis (Δ9-tetrahydrocannabinol), heroin (diamorphine) and antiretrovirals were mixed to mimic a nyaope sample and dissolved in the organic solvents dichloromethane, ethanol, ethyl acetate, hexane, isopropanol and tertiary butyl alcohol. Analysis was performed after intervals of 0, 1, 6, 8, 24, 48 and 72h, prior to analysis by gas chromatography-mass spectrometry. Tertiary butyl alcohol resulted in the most stable extracts of the main nyaope components after 72h of storage. The analysis was also repeated on actual street samples of nyaope. These results show that tertiary butyl alcohol is a suitable solvent for sample preparation for the identification, comparison and profiling of nyaope samples.

Research has demonstrated comorbidity between Attention-Deficit Hyperactivity Disorder (ADHD) and cannabis use, and some have proposed that subclinical ADHD symptoms may explain attentional deficits in cannabis users. Here we investigated whether subclinical ADHD symptoms and cannabis use independently or interactively predict performance on attention tasks in adolescents and young adults.Seventy-two participants (cannabis users (MJ) = 34, Controls = 38) completed neuropsychological tasks of inhibition and attention. Parent report on the Child Behaviors Checklist reflected current ADHD symptoms. Multiple regression analyses examined whether ADHD symptoms and cannabis use independently or interactively predicted cognitive outcomes.Cannabis use was significantly associated with slower CPT hit rate response. Subclinical ADHD symptoms did not independently predict or moderate cannabis effects.Cannabis users demonstrated slower response rate during an attentional task. Subclinical ADHD symptoms did not predict any deficits. As such, attention deficits seen in cannabis users are more related to substance use than ADHD symptomatology.

Marijuana abuse is rapidly growing and currently it is the most coimnon drug of abuse in the United States due to increased legalization for recreational and medicinal use. Delta 9-tetrahydrocannibol, the main psychoactive compound in marijuana, acts via the endocannabinoid system to elicit various cardiovascular physiological effects, and has been associated with many adverse cardiovascular effects such as acute coronary syndrome, arrhythmias, and sudden cardiac death that have previously been reported by our group and others. We present a case of a 30-year-old African-American male with no cardiovascular disease (CVD) risk factors with recurrent ST-segment elevation myocardial infarctions (STEMI) whose coronary angiography revealed recurrent 100% occlusion of the left anterior descending artery (LAD) in the setting of marijuana smoking. It was the patient's third STEMI with 100% occlusion of the LAD with each STEMI secondary to thrombosis of a different region of the LAD. Marijuana use was confirmed by urine toxicology screening at each STEMI presentation. Coronary angiography on multiple occasions was negative for stenosis of other epicardial coronary arteries, and coronary calcimn scoring was zero. Evaluation for other cardiovascular risk factors including family history of premature coronary artery disease, dyslipidemia, diabetes, and hypercoagulable disorders was negative. Further studies are required to elucidate the mechanisms of marijuana-associated coronary thrombosis and myocardial infarction.

Marijuana is the most common drug of abuse in the United States. Marijuana acts on cannabinoid receptors CB1, CB2 and another distinct endothelial receptor. Marijuana is known to cause tachycardia, hypotension and hypertension. Various arrhythmias including atrial fibrillation, atrial flutter, II degree AV block, ventricular fibrillation, ventricular tachycardia, asystole and brugada pattern associated with marijuana use have been reported. We here present an interesting case of Type I Brugada pattern in electrocardiography (ECG) in a 36 year old healthy African American male who presented after smoking four joints. Urine toxicology test proved marijuana use. Acute coronary syndrome was ruled out, coronary angiogram revealed normal coronaries, 2D echocardiogram showed no evidence of structural heart disease. Upon resolution of Brugada pattern in ECG, procainamide challenge performed in electrophysiology laboratory did not induce Brugada pattern. Patient was asked to return to hospital if he developed fever that did not resolve with antipyretics. Further studies are required to to understand the effect of marijuana on cardiac ion channels.

Drug-facilitated sexual assault (DFSA) is a sexual act in which the victim is unable to give or rescind consent due to intoxication with alcohol and/or drugs that have been self-administered (opportunistic DFSA) or covertly administered by the perpetrator (predatory DFSA). The drugs that are most commonly associated with DFSA are flunitrazepam and gamma-hydroxybutyric acid (GHB). They cause sedation and amnesia, are readily dissolved in beverages and are rapidly eliminated from the system. However, drugs such as amphetamine and cocaine, which are central nervous system (CNS) stimulants, have also been encountered in DFSA cases. This paper critically evaluates trend data from cohort studies, identifying drugs that have been detected in DFSA cases and reports on the differences in drugs used between opportunistic and predatory DFSA. This is the first time that a critical multifactorial review of drugs used in DFSA has been conducted. The pharmacology of each identified group of drugs is presented, showing why these compounds are of interest and used in the perpetration of DFSA. Furthermore, the pharmacology and mechanisms of action are described to explain how the drugs cause their effects. It is also apparent from this study that if meaningful data is to be exchanged between law enforcement agencies then it is necessary to agree on protocols for the collection of evidence and the drugs for which analysis should be performed and indeed on the analytical methods used.

Patients with Gilles de la Tourette syndrome (GTS) experience reduced function and impaired quality of life. The current medical treatments for this syndrome can cause significant side effects and offer partial symptomatic relief. In a few small trials medical cannabis (MC) has been suggested to offer symptomatic relief with a relatively benign side effect profile. We conducted a real-life assessment of clinical benefit and adverse effects of chronic MC treatment among patients with GTS.GTS patients treated with MC were interviewed via phone regarding treatment efficacy and side effect profile from chronic MC consumption. Global efficacy was rated on a Likert scale of 1-5 and side effects of treatment were recorded.Forty-Two GTS patients (33 males, mean age 34.5) were interviewed for this study. The total global impression score of efficacy was 3.85 out of a total 5 possible points. Patients reported during the free discussion part of the interview about reduction in tic severity, better sleep and improved mood as positive effects of MC. Thirty-eight patients reported any kind of benefit from treatment while 10 patients with more than one year of consumption elected to stop treatment with MC for various reasons including severe side effects as psychosis in one patient.MC seems to hold promise in the treatment of GTS as it demonstrated high subjective satisfaction by most patients however not without side effects and should be further investigated as a treatment option for this syndrome.

Cannabis consumption is widespread across the world, and the co-occurrence of cannabis use and alcohol consumption is common. The study of background noise - resting-state neural activity, in the absence of stimulation - is an approach that could enable the neurotoxicity of these substances to be explored. Preliminary results have shown that delta-9-tetrahydrocannabinol (Δ9-THC) causes an increase in neural noise in the brain. Neurons in the brain and the retina share a neurotransmission system and have similar anatomical and functional properties. Retinal function, evaluated using an electroretinogram (ERG), may therefore reflect central neurochemistry. This study analyses retinal background noise in a population of regular co-occurrent cannabis and alcohol consumers.We recorded the flash ERGs of 26 healthy controls and 45 regular cannabis consumers, separated into two groups based on their alcohol consumption: less than or equal to 4 glasses per week (CU ≤ 4) or strictly >4 glasses per week (CU >4). In order to extract the background noise, the Fourier transform of the pseudo-periodic and sinusoidal signals of the 3.0 flicker-response sequence was calculated. This sequence represents the vertical transmission of the signal from cones to bipolar cells. The magnitude of the background noise is defined as the average of the magnitudes of the two neighbouring harmonics: harmonic -1 (low frequency noise) and harmonic +1 (high frequency noise).The magnitude of harmonic -1 was significantly increased between the groups CU > 4 (6.78 (±1.24)) and CU ≤ 4 (5.69 (±1.80)) among regular users of cannabis and alcohol. A significant increase in the average magnitude of the two harmonics was found between the groups CU > 4 (5.12 (±0.92)) and CU ≤ 4 (4.36 (±1.14)). No significant difference was observed with regard to the magnitude of the harmonic +1.The increase in background noise may reflect the neurotoxicity of cannabis, potentiated by alcohol consumption, on retinal neurons dynamic. This neural disruption of the response generated by retinal stimulation may be attributable to altered neurotransmitter release.

With the growth of legal cannabis markets there has been recognition of the adverse impacts of certain cannabis growing practices, notably, use of harmful chemicals. A major concern has been the use of Plant Growth Regulators (PGRs) which limit plant size and stimulate bud production. These chemicals, many of which have been banned from food crops, have been found unlisted in cannabis growing nutrients sold online or in hydroponic stores. This study describes the cannabis growing practices used by small-scale recreational cannabis growers and specifically their self-reported use of chemicals.Web survey data from 1722 current and recent cannabis growers in Australia, Denmark, and the UK, who were asked about their cannabis growing practices, including the use of fertilizers and supplements.Overall 44% of the sample reported using any chemical fertilizers, supplements or insecticides. Logistic regression indicated that the unique predictor of the use of chemicals was growing hydroponically.Problems associated with product labeling and uncertainty regarding product constituents made it difficult for growers and the researchers to determine which products likely contained PGRs or other harmful chemicals. There is a need for further research to analyze constituents of chemical products marketed to cannabis growers.

To understand patterns of marijuana use in community-dwelling older adults in Colorado.Anonymous survey.Two academic geriatric primary care clinics.English-speaking individuals.We assessed self-reported characteristics and patterns of marijuana use and effect on targeted symptoms. Survey analysis focused on current users, defined as individuals who had used marijuana in the past 3 years.Three hundred forty-five individuals completed the survey (55% response rate); 113 (32%) had used marijuana in the past, of whom 55 (16%) had used since legalization. More than half of current users were aged 75 and older, and one-quarter were aged 85 and older. Most current users were white women. Of current users, 44% used marijuana products at least weekly for common conditions including chronic pain, depression, anxiety, and insomnia, and most found marijuana helpful for these conditions. Most respondents reported obtaining marijuana recreationally (67%) without a prescription. Nine respondents reported negative side effects attributable to marijuana use.To our knowledge, this is the first study to characterize marijuana use of older adults in a state in which it is legal for medical and recreational use. Marijuana was used for several common geriatric conditions, and respondents reported few side effects. The small number of survey respondents, the lack of generalizability in states where marijuana sales are illegal, and participation bias were the main study limitations. Further research is needed to better understand useful or harmful effects in this population. J Am Geriatr Soc 66:2167-2171, 2018.

Impulsivity is strongly associated with substance use disorders (SUDs). Our review discusses impulsivity as an underlying vulnerability marker for SUDs, and treatment of co-occurring impulsivity in SUDs. Three factors should be considered for the complex relationship between impulsivity and a SUD: (1) the trait effect of impulsivity, centering on decreased cognitive and response inhibition, (2) the state effect resulting from either acute or chronic substance use on brain structure and function, and (3) the genetic and environmental factors (e.g., age and sex) may influence impulsive behavior associated with SUDs. Both subjective and objective measures are used to assess impulsivity. Together, treatment developments (pharmacological, behavioral, and neurophysiological) should consider these clinically relevant dimensions assessed by a variety of measures, which have implications for treatment matching in individuals with SUD. Despite its heterogeneity, impulsivity is a marker associated with SUDs and may be understood as an imbalance of bottom-up and top-down neural systems. Further investigation of these relationships may lead to more effective SUD treatments.

Multiple sclerosis (MS) is an autoimmune disease leading to the destruction of myelin with consequent axonal degeneration and severe physical debilitation. The disease can be treated with immunosuppressive drugs that alleviate the symptoms and retard disease aggravation. One such drug in clinical use is glatiramer acetate (Copaxone). The non-psychotropic immunosuppressive cannabinoid compound cannabidiol (CBD) has recently been shown to have beneficial effects on experimental autoimmune encephalomyelitis (EAE). The aim of our study was to compare the efficacy of CBD and standardized extracts from a CBD-rich, ∆9-THClow Cannabis indica subspecies (Avidekel) with that of Copaxone. Our data show that CBD and purified Avidekel extracts are as efficient as Copaxone to alleviate the symptoms of proteolipid protein (PLP)-induced EAE in SJL/J mice. No synergistic effect was observed by combining CBD or Avidekel extracts with Copaxone. Our data support the use of Avidekel extracts in the treatment of MS symptoms.

Introduction Many patients with cluster headache report use of illicit drugs. We systematically assessed the use of illicit drugs and their effects in a well-defined Dutch cluster headache population. Methods In this cross-sectional explorative study, 756 people with cluster headache received a questionnaire on lifetime use and perceived effects of illicit drugs. Results were compared with age and sex-matched official data from the Dutch general population. Results Compared to the data from the general population, there were more illicit drug users in the cluster headache group (31.7% vs. 23.8%; p < 0.01). Reduction in attack frequency was reported by 56% (n = 22) of psilocybin mushroom, 60% (n = 3) of lysergic acid diethylamide and 50% (n = 2) of heroin users, and a decreased attack duration was reported by 46% (n = 18) of PSI, 50% (n = 2) of heroin and 36% (n = 8) of amphetamine users. Conclusion In the Netherlands, people with cluster headache use illicit drugs more often than the general population. The question remains whether this is due to an actual alleviatory effect, placebo response, conviction, or common pathophysiological background between cluster headache and addictive behaviours such as drug use.

Cannabis sativa is one of the most popular recreational and medicinal plants. Benefits from use of cannabinoid agents in epilepsy, multiple sclerosis, Parkinson's disease, Alzheimer's disease, and others have been suggested. It seems that the endocannabinoid system is also involved in the pathogenesis and treatment of depression, though its role in this mental disease has not been fully understood yet. Both the pro- and antidepressant activity have been reported after cannabis consumption and a number of pre-clinical studies have demonstrated that both agonist and antagonist of the endocannabinoid receptors act similarly to antidepressants. Responses to the cannabinoid agents are relatively fast, and most probably, the noradrenergic, serotoninergic, glutamatergic neurotransmission, neuroprotective activity, as well as modulation of the hypothalamic-pituitary-adrenal axis are implicated in the observed effects. Based on the published data, the endocannabinoid system evidently gives novel ideas and options in the field of antidepressant treatment, however further studies are needed to determine which group of patients could benefit from this type of therapy.

The posterior cingulate cortex (PCC) and precuneus are hubs in the default mode network and play a role in processing external salient stimuli. Accordingly, activation in these regions has been associated with response to salient stimuli using drug cue-reactivity paradigms in substance using populations. These studies suggest that the PCC and precuneus may underlie deficits in processing salient stimuli that contribute toward the development of substance use disorders. The goal of this study was to directly test this hypothesis using repetitive transcranial magnetic stimulation (rTMS). Using a double-blind, placebo-controlled design, we used rTMS to target the PCC and precuneus with a double-cone coil at 10 Hz (high frequency) and 1 Hz (low frequency) in 10 adult cannabis users and 10 age- and sex-matched non-using controls. Electroencephalography data were collected before and after rTMS during a modified oddball paradigm with neutral, oddball, self-relevant, and cannabis-related stimuli. Cannabis users exhibited increased amplitude in P3 and faster latencies in the P3, N2, and P2 components in response to self-relevant stimuli compared to controls during baseline that normalized after rTMS. These results suggest that cannabis users exhibited heightened salience to external self-relevant stimuli that were modulated after rTMS. PCC dysfunction in cannabis users may be related to abnormalities in processing salient stimuli, such those during cue-reactivity, and provides a potential target for cannabis use disorder intervention.

Recent findings suggest an association between tobacco and psychosis, but whether this association is mediated by confounding factors is unknown. Psychosis-like experiences (PLEs) are a subclinical expression of psychosis. To disentangle the association of tobacco with PLEs, we examined data from a large US population-based, nationally representative sample.Analysis was conducted on Wave 2 of the National Epidemiologic Survey of Alcohol and Related Conditions (N = 34,653 adults, conducted from 2004 to 2005). Participants were assessed with the Alcohol Use Disorder and Associated Disabilities Interview Schedule-IV. Twenty-two PLEs previously described as observed indicators of psychosis were used. Participants were stratified according to their smoking status (never/former/current) for 5 different types of tobacco.There was a significant association (ie, with 95% CIs for which the lower value was ≥ 1) between smoking status and 14 of the 22 assessed PLEs. These associations remained significant after adjustment for sociodemographic variables (including urbanicity or ethnicity), lifetime drug use disorder, and past-year cannabis use. While 26.33% of nonsmokers reported at least 1 PLE, this prevalence was slightly higher in former smokers (27.48%) and rose as high as 39.09% in current smokers (for current smokers vs lifetime abstainers, adjusted OR = 1.33; 95% CI, 1.23-1.45). All 22 PLEs had higher prevalence in smokers than in former smokers or lifetime abstainers. A total of 8.56% of smokers reported at least 5 PLEs, compared to 3.42% in lifetime abstainers (aOR = 1.56; 95% CI, 1.32-1.84).In a large population-based, nationally representative sample, smoking status was associated with various PLEs. This association was not explained only by other known risk factors of PLEs or schizophrenia. There is a need to identify the potential neurobiological mechanisms by which smoking and PLEs are associated, for patients and from a public health perspective.

The Iowa Gambling Task (IGT) is widely used to study decision-making within healthy and psychiatric populations. However, the complexity of the IGT makes it difficult to attribute variation in performance to specific cognitive processes. Several cognitive models have been proposed for the IGT in an effort to address this problem, but currently no single model shows optimal performance for both short- and long-term prediction accuracy and parameter recovery. Here, we propose the Outcome-Representation Learning (ORL) model, a novel model that provides the best compromise between competing models. We test the performance of the ORL model on 393 subjects' data collected across multiple research sites, and we show that the ORL reveals distinct patterns of decision-making in substance-using populations. Our work highlights the importance of using multiple model comparison metrics to make valid inference with cognitive models and sheds light on learning mechanisms that play a role in underweighting of rare events.

The relationship between cannabis use and diabetes is puzzling. Although cannabis users versus non-users should theoretically have a higher likelihood of diabetes, epidemiological studies suggest otherwise. However, previous epidemiological studies have not considered the potential confounding effects of mental health disorders. As such, the relationship between cannabis use and diabetes was examined while accounting for a range of potential confounders, including mental health disorders.Data were obtained from the National Epidemiologic Survey on Alcohol and Related Conditions III. Chi-square tests were used to compare socio-demographics, lifestyle behaviours, physical health disorders and mental health disorders between diabetics and non-diabetics. Measures that exhibited statistical significance in these tests were subsequently included in multiple logistic regression analyses to quantify the relationships between lifetime and 12-month cannabis use and diabetes.Although there was a considerable attenuation in the magnitude of the odds ratios after adjustment for confounders, there was still a decreased likelihood of diabetes for cannabis users versus non-users. The corresponding odds ratios of diabetes were 0.81 (95% confidence interval 0.70, 0.94) and 0.51 (95% confidence interval 0.41, 0.63) for lifetime and 12-month cannabis use, respectively.A decreased likelihood of diabetes for cannabis users versus non-users was indicated after accounting for a range of potential confounders, including mental health disorders. Before the protective effects of cannabis use for diabetes can be suggested, further epidemiological studies are needed that incorporate prospective designs, as well as feature innovative exposure measurements and statistical analyses.

Engagement in multiple risk behaviours can have adverse consequences for health during childhood, during adolescence, and later in life, yet little is known about the impact of different types of interventions that target multiple risk behaviours in children and young people, or the differential impact of universal versus targeted approaches. Findings from systematic reviews have been mixed, and effects of these interventions have not been quantitatively estimated.To examine the effects of interventions implemented up to 18 years of age for the primary or secondary prevention of multiple risk behaviours among young people.We searched 11 databases (Australian Education Index; British Education Index; Campbell Library; Cumulative Index to Nursing and Allied Health Literature (CINAHL); Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library; Embase; Education Resource Information Center (ERIC); International Bibliography of the Social Sciences; MEDLINE; PsycINFO; and Sociological Abstracts) on three occasions (2012, 2015, and 14 November 2016)). We conducted handsearches of reference lists, contacted experts in the field, conducted citation searches, and searched websites of relevant organisations.We included randomised controlled trials (RCTs), including cluster RCTs, which aimed to address at least two risk behaviours. Participants were children and young people up to 18 years of age and/or parents, guardians, or carers, as long as the intervention aimed to address involvement in multiple risk behaviours among children and young people up to 18 years of age. However, studies could include outcome data on children > 18 years of age at the time of follow-up. Specifically,we included studies with outcomes collected from those eight to 25 years of age. Further, we included only studies with a combined intervention and follow-up period of six months or longer. We excluded interventions aimed at individuals with clinically diagnosed disorders along with clinical interventions. We categorised interventions according to whether they were conducted at the individual level; the family level; or the school level.We identified a total of 34,680 titles, screened 27,691 articles and assessed 424 full-text articles for eligibility. Two or more review authors independently assessed studies for inclusion in the review, extracted data, and assessed risk of bias.We pooled data in meta-analyses using a random-effects (DerSimonian and Laird) model in RevMan 5.3. For each outcome, we included subgroups related to study type (individual, family, or school level, and universal or targeted approach) and examined effectiveness at up to 12 months' follow-up and over the longer term (> 12 months). We assessed the quality and certainty of evidence using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach.We included in the review a total of 70 eligible studies, of which a substantial proportion were universal school-based studies (n = 28; 40%). Most studies were conducted in the USA (n = 55; 79%). On average, studies aimed to prevent four of the primary behaviours. Behaviours that were most frequently addressed included alcohol use (n = 55), drug use (n = 53), and/or antisocial behaviour (n = 53), followed by tobacco use (n = 42). No studies aimed to prevent self-harm or gambling alongside other behaviours.Evidence suggests that for multiple risk behaviours, universal school-based interventions were beneficial in relation to tobacco use (odds ratio (OR) 0.77, 95% confidence interval (CI) 0.60 to 0.97; n = 9 studies; 15,354 participants) and alcohol use (OR 0.72, 95% CI 0.56 to 0.92; n = 8 studies; 8751 participants; both moderate-quality evidence) compared to a comparator, and that such interventions may be effective in preventing illicit drug use (OR 0.74, 95% CI 0.55 to 1.00; n = 5 studies; 11,058 participants; low-quality evidence) and engagement in any antisocial behaviour (OR 0.81, 95% CI 0.66 to 0.98; n = 13 studies; 20,756 participants; very low-quality evidence) at up to 12 months' follow-up, although there was evidence of moderate to substantial heterogeneity (I² = 49% to 69%). Moderate-quality evidence also showed that multiple risk behaviour universal school-based interventions improved the odds of physical activity (OR 1.32, 95% CI 1.16 to 1.50; I² = 0%; n = 4 studies; 6441 participants). We considered observed effects to be of public health importance when applied at the population level. Evidence was less certain for the effects of such multiple risk behaviour interventions for cannabis use (OR 0.79, 95% CI 0.62 to 1.01; P = 0.06; n = 5 studies; 4140 participants; I² = 0%; moderate-quality evidence), sexual risk behaviours (OR 0.83, 95% CI 0.61 to 1.12; P = 0.22; n = 6 studies; 12,633 participants; I² = 77%; low-quality evidence), and unhealthy diet (OR 0.82, 95% CI 0.64 to 1.06; P = 0.13; n = 3 studies; 6441 participants; I² = 49%; moderate-quality evidence). It is important to note that some evidence supported the positive effects of universal school-level interventions on three or more risk behaviours.For most outcomes of individual- and family-level targeted and universal interventions, moderate- or low-quality evidence suggests little or no effect, although caution is warranted in interpretation because few of these studies were available for comparison (n ≤ 4 studies for each outcome).Seven studies reported adverse effects, which involved evidence suggestive of increased involvement in a risk behaviour among participants receiving the intervention compared to participants given control interventions.We judged the quality of evidence to be moderate or low for most outcomes, primarily owing to concerns around selection, performance, and detection bias and heterogeneity between studies.Available evidence is strongest for universal school-based interventions that target multiple- risk behaviours, demonstrating that they may be effective in preventing engagement in tobacco use, alcohol use, illicit drug use, and antisocial behaviour, and in improving physical activity among young people, but not in preventing other risk behaviours. Results of this review do not provide strong evidence of benefit for family- or individual-level interventions across the risk behaviours studied. However, poor reporting and concerns around the quality of evidence highlight the need for high-quality multiple- risk behaviour intervention studies to further strengthen the evidence base in this field.

The plant Cannabis sativa contains cannabinoids represented by Δ9-tetrahydrocannabinol, which exert psychoactivity and immunomodulation through cannabinoid CB1 and CB2 receptors, respectively, in animal tissues. Arachidonoylethanolamide (also referred to as anandamide) and 2-arachidonoylglycerol (2-AG) are well known as two major endogenous agonists of these receptors (termed "endocannabinoids") and show various cannabimimetic bioactivities. However, only 2-AG is a full agonist for CB1 and CB2 and mediates retrograde signals at the synapse, strongly suggesting that 2-AG is physiologically more important than anandamide. The metabolic pathways of these two endocannabinoids are completely different. 2-AG is mostly produced from inositol phospholipids via diacylglycerol by phospholipase C and diacylglycerol lipase and then degraded by monoacylglycerol lipase. On the other hand, anandamide is concomitantly produced with larger amounts of other N-acylethanolamines via N-acyl-phosphatidylethanolamines (NAPEs). Although this pathway consists of calcium-dependent N-acyltransferase and NAPE-hydrolyzing phospholipase D, recent studies revealed the involvement of several new enzymes. Quantitatively major N-acylethanolamines include palmitoylethanolamide and oleoylethanolamide, which do not bind to cannabinoid receptors but exert anti-inflammatory, analgesic, and anorexic effects through receptors such as peroxisome proliferator-activated receptor α. The biosynthesis of these non-endocannabinoid N-acylethanolamines rather than anandamide may be the primary significance of this pathway. Here, we provide an overview of the biological activities and metabolisms of endocannabinoids (2-AG and anandamide) and non-endocannabinoid N-acylethanolamines.

Selective prevention tackle vulnerable factors associated to problem consumption and social exclusion. There are few effective programs in our context. Study aims were first to identify selective programs of alcohol and cannabis consumption for youths between 16-21, and second, to review intervention, evaluation and effects quality.MEDLINE, PubMed, Google academics, EDDRA, SAMHSA, PBE and recommendations of PND were reviewed. Inclusion criteria were: 1) English/ Spanish programs, 2) publications <10 years, 3) target population 16- 21 years old 4) alcohol/ cannabis psicoeducational or socioeducational programs, 5) selective or selective/indicated programs and 6) evaluated programs. The description and quality of the intervention, its evaluation methods, and the presentation of its effects were assessed according to 20 criteria emerged from different recommendations.Fourteen programs followed the inclusion criteria, 10 of followed minimum quality intervention and evaluation criteria, however only 5 shown significant effects. Effective programs tackled negative emotions associated to consumption, promoted skills to cope it and reduce frequency of alcohol consumption, but rarely cannabis consumption.There are few selective prevention programs, and different studies shown that they have intervention or evaluation weaknesses, but mostly about program effects. The most effective are: PreVenture, The Climate Schools: Alcohol and Cannabis Course, Programa TND, Keepin' it REAL and Weekend is coming.

Treatment with a highly purified oral solution of cannabidiol (CBD), derived from the plant Cannabis sativa L., demonstrated some evidence of central nervous system (CNS)-related adverse events in patients enrolled in phase 3 trials for treatment of childhood-onset epilepsy. Cannabidiol was categorized as a Schedule 1 substance by the United States Drug Enforcement Administration; therefore, it was important to test CBD for human abuse potential.This was a single-dose, randomized, double-blind, double-dummy, placebo- and active-controlled crossover trial. The abuse potential of single oral doses of plant-derived pharmaceutical formulations of highly purified CBD (Epidiolex®; 750 mg, 1500 mg, and 4500 mg) was compared with that of single oral doses of alprazolam (2 mg), dronabinol (10 mg and 30 mg), and placebo in healthy recreational polydrug users. The primary endpoint to assess abuse potential was the maximum effect (Emax) on Drug-Liking visual analog scale (VAS). Other measurements included Emax on Overall Drug-Liking VAS, Take Drug Again VAS, positive and negative effects, other subjective effects, and Drug Similarity VAS. Cognitive and psychomotor functions were assessed using the Divided Attention Test, the Hopkins Verbal Learning Test-Revised, and the Digit-Symbol Substitution Task. Pharmacokinetic parameters were determined for CBD and its major metabolites. Standard safety measures and adverse events were assessed.Of 95 eligible subjects, 43 qualified for the treatment phase, received at least 1 dose of investigational medicinal product, and were included in safety assessments; 35 subjects were included in the pharmacodynamic analysis. Subjects receiving alprazolam and dronabinol had significantly higher Drug-Liking Emax (P < 0.0001) compared with those receiving placebo, confirming study validity. Compared with placebo, Drug-Liking was not significantly different for subjects taking 750-mg CBD (P = 0.51). Drug-Liking Emax values for 1500-mg and 4500-mg CBD were significantly different from placebo (P = 0.04 and 0.002, respectively); however, the mean differences were <10 points on VAS compared with >18-point differences between positive controls and placebo. Alprazolam and dronabinol had significantly higher Drug-Liking, Overall-Liking, and Take Drug Again VAS Emax values compared with all doses of CBD (P ≤ 0.004). In contrast to alprazolam, CBD administration had no observable effect on cognitive/psychomotor tests. Pharmacokinetic parameters for CBD in this trial were consistent with previous studies. The majority of adverse events reported during the trial were of mild or moderate severity; no serious adverse events or deaths were reported.Administration of a therapeutic dose of CBD (750 mg) showed significantly low abuse potential in a highly sensitive population of polydrug users. Although high and supratherapeutic doses of CBD (1500 mg and 4500 mg, respectively) had detectable subjective effects compared with placebo; the effects were significantly lower than those observed with alprazolam and dronabinol.

The human body contains endogenous cannabinoids (endocannabinoids) that elicit effects similar to those of Δ9-tetrahydrocanabinol, the principal bioactive component of cannabis. The endocannabinoid virodhamine (O-AEA) is the constitutional isomer of the well-characterized cardioprotective and anti-inflammatory endocannabinoid anandamide (AEA). The chemical structures of O-AEA and AEA contain arachidonic acid (AA) and ethanolamine; however, AA in O-AEA is connected to ethanolamine via an ester linkage, whereas AA in AEA is connected through an amide linkage. O-AEA is involved in regulating blood pressure and cardiovascular function. We show that O-AEA is found at levels 9.6-fold higher than that of AEA in porcine left ventricle. On a separate note, the cytochrome P450 (CYP) epoxygenase CYP2J2 is the most abundant CYP in the heart where it catalyzes the metabolism of AA and AA-derived eCBs to bioactive epoxides that are involved in diverse cardiovascular functions. Herein, using competitive binding studies, kinetic metabolism measurements, molecular dynamics, and wound healing assays, we have shown that O-AEA is an endogenous inhibitor of CYP2J2 epoxygenase. As a result, the role of O-AEA as an endogenous eCB inhibitor of CYP2J2 may provide a new mode of regulation to control the activity of cardiovascular CYP2J2 in vivo and suggests a potential cross-talk between the cardiovascular endocannabinoids and the cytochrome P450 system.

Evidence suggests that cannabis use, childhood adversity, and urbanicity, in interaction with proxy measures of genetic risk, may facilitate onset of psychosis in the sense of early affective dysregulation becoming 'complicated' by, first, attenuated psychosis and, eventually, full-blown psychotic symptoms.Data were derived from three waves of the second Netherlands Mental Health Survey and Incidence Study (NEMESIS-2). The impact of environmental risk factors (cannabis use, childhood adversity, and urbanicity) was analyzed across severity levels of psychopathology defined by the degree to which affective dysregulation was 'complicated' by low-grade psychotic experiences ('attenuated psychosis' - moderately severe) and, overt psychotic symptoms leading to help-seeking ('clinical psychosis' - most severe). Familial and non-familial strata were defined based on family history of (mostly) affective disorder and used as a proxy for genetic risk in models of family history × environmental risk interaction.In proxy gene-environment interaction analysis, childhood adversity and cannabis use, and to a lesser extent urbanicity, displayed greater-than-additive risk if there was also evidence of familial affective liability. In addition, the interaction contrast ratio grew progressively greater across severity levels of psychosis admixture (none, attenuated psychosis, clinical psychosis) complicating affective dysregulation.Known environmental risks interact with familial evidence of affective liability in driving the level of psychosis admixture in states of early affective dysregulation in the general population, constituting an affective pathway to psychosis. There is interest in decomposing family history of affective liability into the environmental and genetic components that underlie the interactions as shown here.

Treatment for substance use disorders has traditionally been abstinence-oriented, but evaluating the merits of low-level cannabis use as potential treatment endpoint may identify benefits that are clinically relevant for treatment-seeking individuals who do not attain abstinence. This study explores if reduction in cannabis use to a lower level of use is related to improved physical health, mental health, and perceived cognitive functions. Study participants with a history of problematic cannabis use (n = 111) completed assessments. Regression models were used to explore the relationship between past 30-day cannabis use levels (abstinent [57%], low use [22%] defined as less than or equal to 3 days per week, and heavy use [22%] defined as 4 or more days of use per week) and functional status in physical health, mental health, and cognition. Compared to heavy users, both abstinent and low-use individuals were similarly associated with better global health, appetite, and depression outcomes. Abstinent users also reported improved sleep, anxiety, and self-reported cognitive functioning relative to heavy users. Thus, reduction in cannabis use to lower levels is associated with beneficial outcomes important to health and other areas of functioning in individuals with problematic cannabis use.

Cannabidiol (CBD) is 1 of > 100 cannabinoids found in Cannabis sativa L. (Cannabis spp. or Cannabis). Despite its complex and rapidly evolving regulatory status in the United States, projected retail sales of CBD products-hemp, Cannabis and pharmaceutical-are as high as $1.9 billion by 2020. CBD products can currently be purchased online, over the counter, and at Cannabis-specific dispensaries throughout most parts of the country, despite the fact that CBD is presently deemed a Schedule I controlled substance by the U.S. Drug Enforcement Administration and renounced as a dietary supplement ingredient by the U.S. Food and Drug Administration (FDA). These products are largely unregulated, and are being used predominantly to treat specific medical conditions. Recent FDA approval of Epidiolex (CBD) as a treatment for certain pediatric seizure disorders will prompt scheduling of CBD and likely alter FDA enforcement of the Federal Food, Drug, and Cosmetic Act (FD&C), which to date has mostly been in the form of warning letters. Persuasive legal arguments contend that CBD's legal status is based on its source. According to these arguments, there are three legal sources. CBD-derived from: (1) parts of the Cannabis plant that do not meet the definition of cannabis in the Controlled Substances Act (CSA); (2) imported "non-psychoactive hemp"; and (3) "Industrial hemp" cultivated as part of a state pilot program per the 2014 Farm Act. Although CBD's lawful status with respect to the CSA appears to be expanding, its future regulatory status with respect to the FD&C Act is difficult to predict.

The aim of the current study was to investigate what impact a state of alcohol hangover (AH) has upon everyday prospective memory (PM; memory for future events/intentions). Previous research has shown that the AH has a detrimental effect upon cognitive abilities, including memory and attentional deficits. No published research articles to date have focused upon what impact AH might have upon everyday memory, of which PM is a good example. The current study compared an AH group (AHG) with a non-hangover group (NHG) on PM. Since other drug use, anxiety and depression can affect PM independent of the AH, these covariates were controlled for in the study. Fifty-eight young adults studying at university participated in this between-subjects design study-25 in the AHG and 33 in the NHG. The Prospective Remembering Video Procedure (PRVP) measured PM. The Acute Hangover Rating Scale confirmed a state of AH and a Digital Breath Analyzer Test measured their BAC. The Hospital Anxiety and Depression Scale gauged levels of anxiety and depression and a Recreational Drug Use Questionnaire (RDUQ) measured alcohol and other drug use. Anyone who reported having used an illicit substance (e.g., cannabis, ecstasy) or who smoked, were excluded from the study. After controlling for age, alcohol units per week, years spent drinking alcohol, anxiety and depression scores, a one-way analysis of covariance (ANCOVA) revealed that the AHG (mean = 5.16) recalled significantly fewer items on the PRVP than the NHG (mean = 7.51)-F(1,52) = 5.69, p < 0.05. Overall, it appeared that a state of AH significantly impaired PM, which was not attributable to age, alcohol use, or anxiety or depression indices. Given the importance of PM to everyday activities, such as remembering to keep appointments or to take an important medication on time, this finding may have farther-reaching implications. These findings should also be used to educate young adults and health professionals dealing with the consequences with regards the dangers of alcohol misuse.

Neuronal circuits within the prefrontal cortex (PFC) mediate higher cognitive functions and emotional regulation that are disrupted in psychiatric disorders. The PFC undergoes significant maturation during adolescence, a period when cannabis use in humans has been linked to subsequent vulnerability to psychiatric disorders such as addiction and schizophrenia. Here, we investigated in a rat model the effects of adolescent exposure to Δ9-tetrahydrocannabinol (THC), a psychoactive component of cannabis, on the morphological architecture and transcriptional profile of layer III pyramidal neurons-using cell type- and layer-specific high-resolution microscopy, laser capture microdissection and next-generation RNA-sequencing. The results confirmed known normal expansions in basal dendritic arborization and dendritic spine pruning during the transition from late adolescence to early adulthood that were accompanied by differential expression of gene networks associated with neurodevelopment in control animals. In contrast, THC exposure disrupted the normal developmental process by inducing premature pruning of dendritic spines and allostatic atrophy of dendritic arborization in early adulthood. Surprisingly, there was minimal overlap of the developmental transcriptomes between THC- and vehicle-exposed rats. THC altered functional gene networks related to cell morphogenesis, dendritic development, and cytoskeleton organization. Marked developmental network disturbances were evident for epigenetic regulators with enhanced co-expression of chromatin- and dendrite-related genes in THC-treated animals. Dysregulated PFC co-expression networks common to both the THC-treated animals and patients with schizophrenia were enriched for cytoskeletal and neurite development. Overall, adolescent THC exposure altered the morphological and transcriptional trajectory of PFC pyramidal neurons, which could enhance vulnerability to psychiatric disorders.

The legal Australian cannabis industry has been rapidly expanding due to increased awareness of the plant's therapeutic potential, as well its diverse range of applications including biofuel, textiles, building materials, food, nutritional supplement, and animal feed. The objective of this paper is to describe the current landscape of the commercial Australian cannabis industry, summarise occupational health and safety (OHS) hazards in cannabis-related working environments, and provide suggestions for safeguarding worker health and well-being in this emerging industry. A comprehensive search of peer-reviewed and grey literature published between 1900 and 2017 was undertaken to identify case studies and original epidemiological research on OHS hazards associated with the cannabis cultivation and the manufacture of cannabis-based products. The review found that the majority of OHS studies were undertaken in the hemp textile industry during the late twentieth century, with a small number of articles published from a variety of occupational environments including forensic laboratories and recreational marijuana farms. Cannabis harvesting and initial processing is labour intensive, and presents a physical hazard Depending on the operation, workers may also be exposed to a variety of biological, chemical, and physical hazards including: organic dusts, bioaerosols, pollen/allergens, volatile organic compounds, psychoactive substances (tetrahydrocannabinol [THC])), noise, and ultraviolet radiation. Little research has been undertaken on the exposure to inhalable organic dust and other bioaerosols during the commercial cultivation and manufacture of cannabis-based products. Furthermore, there is an absence of Australian-based research and OHS guidance materials to help professionals develop risk management strategies in this evolving industry. It is recommended that: Investigation into the toxicological properties of cannabis dusts, specifically in relation to potential occupational exposures during cultivation and manufacture, should be a priority. The interim adoption of the respirable cotton dust exposure standard of 0.2 mg/m3 for workplace exposure in hemp facilities until a cannabis workplace exposure standard is developed, and that exposure to medicinal cannabis containing THC are kept as low as reasonably practicable. An industry partnership be established for the development of an Australian health and safety guideline for the production of medicinal cannabis and hemp. A classification to meet the requirements of the Global Harmonization Scheme should be undertaken to ensure consistency in the use of safety and risk phrases in cannabis-related industries.

Following the discovery of the endocannabinoid system and its potential as a therapeutic target for various pathological conditions, growing interest led researchers to investigate the role of cannabis and its derivatives for medical purposes. The compounds Δ9-tetrahydrocannabinol and cannabidiol are the most abundant phytocannabinoids found in cannabis extracts, as well as the most studied. The present review aims to provide an overview of the current evidence for their beneficial effects in treating psychiatric disorders, including schizophrenia, anxiety, and depression. Nevertheless, further investigations are required to clarify many pending issues, especially those relative to the assessment of benefits and risks when using cannabis for therapeutic purposes, thereby also helping national and federal jurisdictions to remain updated.

Alcohol and cannabis misuse are related to impaired cognition. When inferring causality, four nonexclusive theoretical models can account for this association: 1) a common underlying vulnerability model; 2) a neuroplasticity model in which impairment is concurrent with changes in substance use but temporary because of neuroplastic brain processes that restore function; 3) a neurotoxicity model of long-term impairment consequential to substance use; and 4) a developmental sensitivity hypothesis of age-specific effects. Using a developmentally sensitive design, the authors investigated relationships between year-to-year changes in substance use and cognitive development.A population-based sample of 3,826 seventh-grade students from 31 schools consisting of 5% of all students entering high school in 2012 and 2013 in the Greater Montreal region were assessed annually for 4 years on alcohol and cannabis use, recall memory, perceptual reasoning, inhibition, and working memory, using school-based computerized assessments. Multilevel regression models, performed separately for each substance, were used to simultaneously test vulnerability (between-subject) and concurrent and lagged within-subject effects on each cognitive domain.Common vulnerability effects were detected for cannabis and alcohol on all domains. Cannabis use, but not alcohol consumption, showed lagged (neurotoxic) effects on inhibitory control and working memory and concurrent effects on delayed memory recall and perceptual reasoning (with some evidence of developmental sensitivity). Cannabis effects were independent of any alcohol effects.Beyond the role of cognition in vulnerability to substance use, the concurrent and lasting effects of adolescent cannabis use can be observed on important cognitive functions and appear to be more pronounced than those observed for alcohol.

The aim of this study was to describe the demographic and clinico-pathological characteristics of lung cancer in patients younger than 40 years.This was a prospective study performed within the Groupe Français de Pneumo-Cancérologie. Consecutive patients diagnosed with lung cancer before the age of 40 years were eligible. Data on demographics, medical history, clinico-pathological characteristics, treatment and overall survival were analysed.In total, 146 patients were included from January 2011 to December 2013. Median age was 38 years (IQR: 34-40). Women accounted for 41%. Main histological type was adenocarcinoma (77%). Only 3% had a prior history of cancer, but a family history (first- or second-degree relatives) of cancer was reported in 80 (55%) patients; 85 and 50% were current or past smokers of tobacco and cannabis, respectively; 82% had stage IIIB/IV at diagnosis. Median overall survival was 15.3 (95% CI: 8.1-24.0) months in the whole population, 10.3 (95% CI: 12.5-14.2) months in stage IV and 15 (95% CI: 8.7-35.2) months in stage III. One- and two-year overall survival rates were 57% (95 CI: 49-65) and 31.5% (95 CI: 27-43), respectively. Compared to smokers, non-smokers were significantly younger and more often females. Median overall survival was not statistically different between smokers and non-smokers.

Recent studies have explored how professionals draw boundaries to reach workable solutions in conflictual and contested areas. Yet they neglected to explore the relationships and dynamics between how boundaries are demarcated in rhetoric and in policy. This article examines these relationships empirically through the case of medical cannabis (MC) policy-making in Israel. Drawing on interviews with key stakeholders in the MC policy field, formal policy documents, and observations of MC conferences, this article sheds light on the dynamics between rhetorical boundary-work and what we term regulatory boundary-work, namely setting rules and regulations to demarcate boundaries in actual practice. Results show how certain definitions of and rationales for a discursive separation between "medical" and "recreational" cannabis and between cannabis "medicalization" and "legalization" prevailed and were translated into formal policy, as well as how stakeholders' reactions to this boundary-work produced policy changes and the shifting of boundaries. Both rhetorical and regulatory boundary-works emerge as ongoing contested processes of negotiation, which are linked in a pattern of reciprocal influence. These processes are dominated by certain actors who have greater power to determine how and why specific boundaries should be drawn instead of others.

To examine, through a cross-sectional survey, how well safety information was reported among drug systematic reviews predating PRISMA harms checklist and explore factors associated with better reporting.We searched PubMed to identify all systematic reviews published in the Cochrane Database of Systematic Review or the core clinical journals in 2015, one year before the PRISMA harms checklist was published. We randomly selected, in a 1:1 ratio, Cochrane and non-Cochrane systematic reviews assessing drug effects (including both efficacy and safety). We used the PRISMA harms checklist published in 2016 to assess the quality of reporting of drug safety information. Multivariable linear regression analyses were used to explore the association of six prespecified variables with more complete reporting of PRISMA harms items.We included 120 systematic reviews, including 60 Cochrane and 60 non-Cochrane reviews. Scores on the PRISMA harms checklist (23 items) were low (median 4, [first, third quartile: 2, 6]), with no difference between Cochrane and non-Cochrane reviews (4.5 [2, 7] vs. 4 [2.5, 5]; P = 0.29). Among all eligible reviews, only one item (i.e., state conclusions in coherence with the review findings) was reported adequately (proportion of adherence 81.6%); proportion of reporting for other items ranged from 1.7% to 68.3%. The four essential reporting items from PRISMA harms checklist were also poorly complied (proportion of adherence ranged from 1.7% to 9.2%). Multivariable linear regression analyses found no significant associations between any study characteristic and reporting on the PRISMA harms, likely because of limited variability in scores across studies.The reporting of safety information was poor both for Cochrane and non-Cochrane drug systematic reviews predating PRISMA harms checklist. The findings suggested a strong need to use the PRISMA harms checklist for reporting safety among drug systematic reviews.

The transition from voluntary to addictive behavior is characterized by a loss of regulatory control in favor of reward driven behavior. Animal models indicate that this process is neurally underpinned by a shift in ventral-dorsal striatal control of behavior; however, this shift has not been directly examined in humans. The present resting state functional magnetic resonance imaging (fMRI) study employed a two-step approach to: (a) precisely map striatal alterations using a novel, data-driven network classification strategy combining intrinsic connectivity contrast with multivoxel pattern analysis and, (b) to determine whether a ventral to dorsal striatal shift in connectivity with reward and regulatory control regions can be observed in abstinent (28 days) male cannabis-dependent individuals (n = 24) relative to matched controls (n = 28). Network classification revealed that the groups can be reliably discriminated by global connectivity profiles of two striatal regions that mapped onto the ventral (nucleus accumbens) and dorsal striatum (caudate). Subsequent functional connectivity analysis demonstrated a relative shift between ventral and dorsal striatal communication with fronto-limbic regions that have been consistently involved in reward processing (rostral anterior cingulate cortex [ACC]) and executive/regulatory functions (dorsomedial prefrontal cortex [PFC]). Specifically, in the cannabis-dependent subjects, connectivity between the ventral striatum with the rostral ACC increased, whereas both striatal regions were uncoupled from the regulatory dorsomedial PFC. Together, these findings suggest a shift in the balance between dorsal and ventral striatal control in cannabis dependence. Similar changes have been observed in animal models and may promote the loss of control central to addictive behavior.

We tested the age-varying associations of cannabis use (CU) frequency and disorder (CUD) with psychotic, depressive and anxiety symptoms in adolescent and adult samples. Moderating effects of early onset (≤ 15 years) and sex were tested.Time-varying effect models were used to assess the significance of concurrent associations between CU and CUD and symptoms of psychosis, depression and anxiety at each age.Adolescent data (V-HYS; n = 662) were collected from a randomly recruited sample of adolescents in Victoria, British Columbia, Canada during a 10-year period (2003-13). Adult cross-sectional data (NESARC-III; n = 36 309) were collected from a representative sample from the United States (2012-13).Mental health symptoms were assessed using self-report measures of diagnostic symptoms. CU was based on frequency of past-year use. Past-year CUD was based on DSM-5 criteria.For youth in the V-HYS, CU was associated with psychotic symptoms following age 22 [b = 0.13, 95% confidence interval (CI) = 0.002, 0.25], with depressive symptoms from ages 16-19 and following age 25 (b = 0.17, 95% CI = 0.003, 0.34), but not with anxiety symptoms. CUD was associated with psychotic symptoms following age 23 (b = 0.51, 95% CI = 0.01, 1.01), depressive symptoms at ages 19-20 and following age 25 (b = 0.71, 95% CI = 0.001, 1.42) and anxiety symptoms ages 26-27 only. For adults in the NESARC-III, CU was associated with mental health symptoms at most ages [e.g. psychotic symptoms; age 18 (b = 0.22, 95% CI = 0.10, 0.33) to age 65 (b = 0.36, 95% CI = 0.16, 0.56)]. CUD was associated with all mental health symptoms across most ages [e.g. depressive symptoms; age 18 (b = 0.96, 95% CI = 0.19, 1.73) to age 61 (b = 1.11, 95% CI = 0.01, 2.21)]. Interactions with sex show stronger associations for females than males in young adulthood [e.g.CUD × sex interaction on psychotic symptoms significant after age 26 (b = 1.12, 95% CI = 0.02, 2.21)]. Findings were not moderated by early-onset CU.Significant associations between cannabis use (CU) frequency and disorder (CUD) and psychotic and depressive symptoms in late adolescence and young adulthood extend across adulthood, and include anxiety.

Cannabis is becoming increasingly present in our society. In recent years, the line between the natural (cannabis) and the synthetic (synthetic cannabinoids), the recreational (cannabis) and the medical (pharmaceutical cannabinoids and medical cannabis) has been crossed. In this paper we review some of the novel aspects of cannabis and cannabinoids in relation to their legal situation, changes in their composition and forms of cannabis use, the concept of medical cannabis, and synthetic cannabinoids as new psychoactive substances (NPS). We have also analyzed serious adverse reactions and intoxications associated with the use of synthetic cannabinoids, as well as the latest developments in the research of pharmaceutical cannabinoids.

There is evidence that regular cannabis use has negative effects on sleep health. Relative to HIV- populations, HIV + individuals consistently report greater sleep impairments. The number of HIV + individuals reporting frequent cannabis use, often to treat sleep issues, has significantly increased recently. It is unknown, however, if HIV status moderates the association between cannabis use and sleep health. The current study, therefore, examines these associations in a sample of HIV + and HIV- adults.HIV + and HIV- (N = 107) individuals completed one laboratory visit. Participants completed a 30-day drug use history questionnaire quantifying consumption of cannabis, cigarettes, and alcohol, and a sleep health questionnaire. To verify substance use and HIV status, participants completed a urine toxicology screening and serology testing.HIV + individuals demonstrated lower sleep health than HIV- individuals. Linear regressions indicated that HIV status moderated the association between total 30-day cannabis consumption and sleep health; cannabis consumption was negatively associated with sleep health in HIV-, but not HIV + individuals. This interactive effect was significant after examining cigarette/alcohol use, depression symptoms, and demographic variables as covariates.These results corroborate studies demonstrating an inverse relationship between sleep health and cannabis consumption. This study also suggests that factors other than cannabis may be associated with lower sleep health in HIV + individuals. Emerging studies suggest that inflammation may mediate effects of cannabis on HIV infection. Future studies examining this mechanism are warranted to understand cannabis further and sleep in HIV + individuals.

Cannabis allergy (CA) has mainly been attributed to Can s 3, the nonspecific lipid transfer protein (nsLTP) of Cannabis sativa. Nevertheless, standardized diagnostic tests are lacking and research on CA is scarce.To explore the performance of 5 cannabis diagnostic tests and the phenotypic profile of CA.A total of 120 patients with CA were included and stratified according to the nature of their cannabis-related symptoms; 62 healthy and 189 atopic controls were included. Specific IgE (sIgE) hemp, sIgE and basophil activation test (BAT) with a recombinant Can s 3 protein from Cannabis sativa (rCan s 3), BAT with a crude cannabis extract, and a skin prick test (SPT) with an nCan s 3-rich cannabis extract were performed. Clinical information was based on patient history and a standardized questionnaire.First, up to 72% of CA reporting likely-anaphylaxis (CA-A) are Can s 3 sensitized. Actually, the Can s 3-based diagnostic tests show the best combination of positive and negative predictive values, 80% and 60%, respectively. sIgE hemp displays 82% sensitivity but only 32% specificity. Secondly, Can s 3+CA reported significantly more cofactor-mediated reactions and displayed significantly more sensitizations to other nsLTPs than Can s 3-CA. Finally, the highest prevalence of systemic reactions to plant-derived foods was seen in CA-A, namely 72%.The most effective and practical tests to confirm CA are the SPT with an nCan s 3-rich extract and the sIgE rCan s 3. Can s 3 sensitization entails a risk of systemic reactions to plant-derived foods and cofactor-mediated reactions. However, as Can s 3 sensitization is not absolute, other cannabis allergens probably play a role.

With the issuance of this final order, the Acting Administrator of the Drug Enforcement Administration places certain drug products that have been approved by the Food and Drug Administration (FDA) and which contain cannabidiol (CBD) in schedule V of the Controlled Substances Act (CSA). Specifically, this order places FDA-approved drugs that contain CBD derived from cannabis and no more than 0.1 percent tetrahydrocannabinols in schedule V. This action is required to satisfy the responsibility of the Acting Administrator under the CSA to place a drug in the schedule he deems most appropriate to carry out United States obligations under the Single Convention on Narcotic Drugs, 1961. Also consistent therewith, DEA is adding such drugs to the list of substances that may only be imported or exported pursuant to a permit.

Injury deaths have a major impact on public health systems, particularly in the Latin American region; however, little is known about how different drugs, in combination or not with alcohol, interact with each injury type. We tested an epidemiological protocol for investigating alcohol and other drug acute use among fatally injured victims taking into account the injury context for all injury causes in Sao Paulo, Brazil. Blood alcohol and drug content were fully screened and confirmed following a probability sample selection of decedents (n = 365) during 19 consecutive months (2014-2015). Drug concentrations, including benzodiazepines, cannabis, cocaine, and opioids were determined by gas chromatography-mass spectrometry (GC-MS) or liquid chromatography tandem mass spectrometry (LC-MS/MS). Toxicology data were interpreted in combination with injury context retrieved from police records regarding cause, place of injury, and victims' criminal history. More than half of all fatally injured victims studied were under the influence of at least one substance (55.3%). Alcohol was the leading substance consumed before a fatal injury event (30.1%), followed by cocaine (21.9%) and cannabis (14%). Illicit drug use (cocaine and cannabis) comprised more than two thirds of all drug-related deaths. Alcohol-positive deaths are over-represented among road traffic injuries, while drug-positive deaths are more prevalent among intentional injuries. Victims who had previous criminal convictions were significantly more likely to have used illicit drugs compared to those who did not have a criminal background. We estimated that one in every two fatal injuries in the city of Sao Paulo is associated with acute substance use by the victim. The health burden attributed to alcohol- and drug-related fatal injury events has reached significant higher levels in Latin American cities such as Sao Paulo compared globally.

To identify the common aeroallergens causing allergy symptoms among the allergic rhinitis patients.Cross-sectional study.Department of Immunology, Armed Forces Institute of Pathology (AFIP), Rawalpindi, from January to July 2016.Patients with a clinical diagnosis of allergic rhinitis were enrolled. Skin Prick Test (SPT) was performed on these patients using 12 common aeroallergens along with positive (histamine hydrochloride, 10 mg/ml) and negative (glycerin saline) controls. Results were recorded after 15 minutes, considering a wheal diameter >3 mm as positive. Chi-square test was used to compare frequencies; and p-value of less than 0.05 was considered significant.Out of 130 patients, 78 (60%) were males and 52 (40%) were females. The rate of sensitization to any allergen was 90%. One hundred and two (78%) were poly-sensitized to more than two allergens and 20% were sensitized to more than six allergens. Most common outdoor and indoor allergens were Broussonetia papyrifera (50.7%) and Dermatophagoides farina (42.3%), respectively. Dog epithelia and aspergillus were the least prevalent allergens (13.8% each).This study highlighted an increased overall frequency of sensitization to any allergen and significance of tree and weed allergens; especially, Broussonetia papyrifera and Cannabis sativa. It also emphasized increased prevalence of skin reactivity to indoor allergen, Dermatophagoides farina in the city.

Individuals with psychotic-spectrum disorders use tobacco and cannabis at higher rates than the general population and individuals with other psychiatric disorders, which may contribute to increased rates of medical problems and mortality. The present study examined whether individuals with psychosis and comorbid tobacco and/or cannabis use disorders exhibit differing clinical characteristics in terms of their sociodemographic, mental health, substance use, physical health, and medication use patterns. Elucidation of these profiles, and determining their relative severity, has important implications for treatment, including offering more targeted interventions based on type of comorbidity pattern.We examined the electronic medical records of 829 patients with psychotic-spectrum disorders admitted to a psychiatric hospital and categorized them as having: (1) cannabis use disorder (CUD); (2) tobacco use disorder (TUD); (3) comorbid cannabis and tobacco use disorders (CUD + TUD); or (4) neither disorder (no CUD/TUD). Multinomial logistic regression was used to compare the aforementioned groups on multiple variables controlling for age and sex.Alcohol and stimulant use disorder diagnoses were each related to higher odds of having a CUD and CUD + TUD, relative to no CUD/TUD. Stimulant and polysubstance use disorder diagnoses were each related to higher odds of having a TUD compared to no CUD/TUD. Greater number of prescribed psychotropic medications was related to higher odds of a TUD compared to no CUD/TUD.Although several differences between groups were accounted for by age of cannabis versus tobacco users, findings point to the importance of considering comorbid alcohol and substance use disorders among those with psychosis and CUD/TUD, as these comorbidities have important implications for screening and treatment selection during and following acute hospitalization.