Lung cancer is the most common cancer in men living Eastern Morocco. We here present the first report on the clinical, pathological and therapeutic features of lung cancer in Eastern Morocco.We conducted a retrospective study of 738 patients diagnosed with lung cancer at the Hassan II, Oncology Center between October 2005 and December 2014.Among the cases studied, 671 patients were men and 67 women; 95.01% of men and 1.54% of women were smokers. The average age of patients was 59.1 ± 11.9 years. Most patients (97%) were diagnosed at advanced stage disease. Only 4 out of 227 patients with advanced adenocarcinoma underwent molecular test. In addition, no patient in our series received targeted therapy. In this series, 20.46% of patients had less than 50 years. Compared to patients aged 50 years and older, cannabis consumption was higher (p<0.001) in patients less than 50 years and as well as a higher rate of adenocarcinoma (p<0.01). By contrast, in these patients, tobacco consumption was lower (p<0.001) as well as the rate of squamous cell carcinoma (p<0.01) and small cell cancer (p<0.05).Unlike Western countries, in Eastern Morocco lung cancer is diagnosed late, affects younger people and access to molecular tests is still very limited. These results justify the need to implement effective programs against lung cancer as well as to facilitate access to molecular tests and new therapeutic tools in Eastern Morocco.

Since August 2019, more than 2700 patients have been hospitalized with e-cigarette, or vaping, product use-associated lung injury (EVALI) across the United States. This report describes the outbreak in California, a state with one of the highest case counts and with a legal adult-use (recreational) cannabis market.To present clinical characteristics and vaping product exposures of patients with EVALI in California.Case series describing epidemiologic and laboratory data from 160 hospitalized patients with EVALI reported to the California Department of Public Health by local health departments, who received reports from treating clinicians, from August 7 through November 8, 2019.Standardized patient interviews were conducted to assess vaping products used, frequency of use, and method of product acquisition. Vaping products provided by a subset of patients were tested for active ingredients and other substances.Demographic and clinical characteristics, level of care, and outcomes of hospitalization were obtained from medical record review.Among 160 patients with EVALI, 99 (62%) were male, and the median age was 27 years (range, 14-70 years). Of 156 patients with data available, 71 (46%) were admitted to an intensive care unit, and 46 (29%) required mechanical ventilation. Four in-hospital deaths occurred. Of 86 patients interviewed, 71 (83%) reported vaping tetrahydrocannabinol (THC)-containing products, 36 (43%) cannabidiol (CBD)-containing products, and 39 (47%) nicotine-containing products. Sixty-five of 87 (75%) THC-containing products were reported as obtained from informal sources, such as friends, acquaintances, or unlicensed retailers. Of 87 vaping products tested from 24 patients, 49 (56%) contained THC. Vitamin E or vitamin E acetate was found in 41 (84%) of the THC-containing products and no nicotine products.Patients' clinical outcomes and vaping behaviors, including predominant use of THC-containing products from informal sources, are similar to those reported by other states, despite California's legal recreational cannabis market. While most THC products tested contained vitamin E or vitamin E acetate, other underlying cause(s) of injury remain possible. The California Department of Public Health recommends that individuals refrain from using any vaping or e-cigarette products, particularly THC-containing products from informal sources, while this investigation is ongoing.

Cannabis abstinence traditionally is the primary outcome in cannabis use disorder (CUD) treatment trials. Due to the changing legality of cannabis, patient goals, and preliminary evidence that suggests individuals who reduce their cannabis use may show functional improvements, cannabis reduction is a desirable alternative outcome in CUD trials. We review challenges in measuring cannabis reduction and the evidence to support various definitions of reduction.Reduction in number of cannabis use days was associated with improvements in functioning across several studies. Reductions in quantity of cannabis used was inconsistently associated with improvements in functioning, though definitions of quantity varied across studies. Different biomarkers may be used depending on the reduction outcome.Biologically-confirmed reductions in frequency of cannabis use days may represent a viable endpoint in clinical trials for cannabis use disorder. Additional research is needed to better quantify reduction in cannabis amounts.

Current treatments for primary psychotic disorders include antipsychotics, some of which have significant side effects or suboptimal efficacy. Cannabidiol is a cannabinoid with potential antipsychotic properties. This systematic review examines the use of cannabidiol as an antipsychotic treatment for primary psychotic disorders. CINAHL, EBM, EMBASE, MEDLINE and PubMed databases were searched from 1970 to 2019 for experimental and observational studies evaluating the antipsychotic and cognitive modulation properties of cannabidiol in individuals with psychotic disorders. There were eight eligible studies evaluating the antipsychotic potential of cannabidiol, involving a total of 210 participants. Due to study heterogeneity, we present the extracted data on general psychopathology, positive and negative symptoms, cognition and functioning outcomes as a narrative synthesis. We found limited evidence supporting antipsychotic efficacy for cannabidiol and none supporting its benefits for cognition or functioning. Cannabidiol treatment had an advantageous side effect profile compared to other antipsychotics and was well tolerated across studies. Observational studies had a higher risk of bias than experimental studies. Factors potentially contributing to variability in outcome results included cannabidiol dosage, treatment duration, use as an adjunctive treatment and participant inclusion criteria, which warrant further investigation to determine whether cannabidiol can be effective as a treatment for psychosis.

Cannabis use disorder (CUD) is a growing concern, and evidence-based data are needed to inform treatment options.To review the benefits and risks of pharmacotherapies for the treatment of CUD.MEDLINE, PsycINFO, Cochrane Database of Systematic Reviews, and clinical trial registries from inception through September 2019.Pharmacotherapy trials of adults or adolescents with CUD that targeted cannabis abstinence or reduction, treatment retention, withdrawal symptoms, and other outcomes.Data were abstracted by 1 investigator and confirmed by a second. Study quality was dually assessed, and strength of evidence (SOE) was determined by consensus according to standard criteria.Across 26 trials, the evidence was largely insufficient. Low-strength evidence was found that selective serotonin reuptake inhibitors (SSRIs) do not reduce cannabis use or improve treatment retention. Low- to moderate-strength evidence was found that buspirone does not improve outcomes and that cannabinoids do not increase abstinence rates (moderate SOE), reduce cannabis use (low SOE), or increase treatment retention (low SOE). Across all drug studies, no consistent evidence of increased harm was found.Few methodologically rigorous trials have been done. Existing trials are hampered by small sample sizes, high attrition rates, and heterogeneity of concurrent interventions and outcomes assessment.Although data on pharmacologic interventions for CUD are scarce, evidence exists that several drug classes, including cannabinoids and SSRIs, are ineffective. Because of increasing access to and use of cannabis in the general population, along with a high prevalence of CUD among current cannabis users, an urgent need exists for more research to identify effective pharmacologic treatments.U.S. Department of Veterans Affairs. (PROSPERO: CRD42018108064).

The purpose of the study was to describe the relationship between substance use and impulsivity according to gender as a moderating variable in a sample of Argentine students. Three hundred ninety students were evaluated using a sociodemographic and clinical ad hoc questionnaire; the ASSIST test and the Barratt scale were used to detect substance use and impulsiveness levels respectively. Equal percentages of men and women use alcohol and tobacco; a greater proportion of men use cannabis. Impulsivity levels are higher among teenagers who use substances. Women who use substances (alcohol, tobacco and cannabis) are more impulsive than male users, specifically from the motor point of view. The relationship between impulsivity and substance use is confirmed, gender issues could mediate this relationship and underlying biological mechanisms; these findings will allow a differential gender approach to be established regarding drug prevention and treatment.

To summarize evidence relating cannabis smoking and oral disease and highlight any potential influence of cannabis smoking on clinical care and dental public health.Using rapid evidence review, a librarian facilitated a systematic search of 5 electronic databases in August and September 2018 and updated it in March 2019, yielding 581 publications. Two researchers screened the documents using pre-established inclusion criteria: article was based on primary or secondary data; cannabis smoking was an exposure; at least 1 cannabis-related oral health outcome was reported; participants were humans; and the article was available in English or French. Data from retained articles were analyzed for themes without meta-analysis.We synthesized and summarized 23 articles in 2 broad categories: cannabis and oral disease; and cannabis, clinical care and dental public health. Current evidence shows that smoking cannabis is harmful to the health of the periodontium. The association between smoking cannabis and other oral disease (dental caries, soft tissue lesions and oral cancers) is sparse and inconsistent, although studies suggest that cannabis smoking is an underlying risk factor. Cannabis smoking can lead to an altered mental state that can delay dental treatment of the patient. Further, interactions between smoked cannabis and adrenaline-containing local anesthetics can result in life-threatening consequences.Cannabis smoking is harmful to the periodontium. Further research is needed to fully understand how cannabis smoking affects oral disease and how dental professionals should integrate this knowledge into clinical care and dental public health.

Cannabidiol (CBD)-containing products are widely marketed as over the counter products, mostly as food supplements, to avoid the strict rules of medicinal products. Side-effects reported in anecdotal consumer reports or during clinical studies were first assumed to be due to hydrolytic conversion of CBD to psychoactive Δ 9-tetrahydrocannainol (THC). However, research of pure CBD solutions stored in simulated gastric juice or subjected to various storage conditions such as heat and light with specific liquid chromatographic/tandem mass spectrometric (LC/MS/MS) and ultra-high pressure liquid chromatographic/quadrupole time-of-flight mass spectrometric (UPLC-QTOF) analyses was unable to confirm THC formation. Another hypothesis for the side-effects of CBD products may be residual THC concentrations in the products as contamination, because most of them are based on crude hemp extracts containing the full spectrum of cannabinoids besides CBD. Analyses of 28 food products of the German market containing hemp extract as an ingredient (mostly CBD oils) confirmed this hypothesis: 10 products (36%) contained THC above the lowest observed adverse effects level (2.5 mg/day). Inversely, CBD was present in the products below the no observed adverse effect level. Hence, it may be assumed that the adverse effects of some commercial CBD products are based on a low-dose effect of THC and not due to effects of CBD itself. The safety, efficacy and purity of commercial CBD products is highly questionable, and all of the products in our sample collection showed various non-conformities to European food law such as unsafe THC levels, full-spectrum hemp extracts as non-approved novel food ingredients, non-approved health claims, and deficits in mandatory food labelling requirements. In view of the growing market for such lifestyle products, the effectiveness of the instrument of food business operators' own responsibility for product safety must obviously be challenged.

In recent years, there has been an increase in the non-medical use of psychoactive prescription drugs including pregabalin (PGB). Studies have shown that multiple drug users and patients in methadone treatment programs administered PGB at high dosages in order to achieve euphoria, reduce withdrawal symptoms, or potentiate the effects of methadone. For these reasons, accurate toxicological monitoring is required for these high-risk individuals.The present study investigated whether PGB could be detected in the hair samples of 250 patients with a history of opiate dependency, and under toxicological surveillance assess their compliance with methadone maintenance therapy.Opiates were found in 54/250 of all hair samples, while cannabis was present in 74/250 patients, cocaine was detected in 21/250 patients, and benzodiazepines without prescription were identified in 49/250 patients. As expected, methadone was present in all 250 patients (100%). PGB without prescription was found in the hair samples of 35/250 patients (14%). Of these, 91.43% were male, 48.57% were <30 y old, and 45.71% were between ages 30 and 50 y. There were no apparent associations among PGB use, daily methadone dosage, and duration of methadone maintenance therapy. Psychiatric comorbidities were present in 25.71% of the patients abusing PGB. Anxiety (55.56%) and depression (33.33%) were the most prevalent psychiatric disorders.Most of the patients taking PGB (57.14%) used other drugs (especially opiates) concurrently. The utility of hair analysis is explained by easy and rapid sample collection and the ability of the hair to reflect long-term drug use and incorporate drug metabolites. The findings of this study suggested that PGB has significant potential for abuse by high-risk populations such as opioid users and patients with dual diagnosis. These risks are particularly high in cases of poly-drug use and drug intake that are not in compliance with prescription guidelines.

With its legalisation and regulation in Canada in 2018, the proportion of Canadians reporting cannabis use in 2019 increased substantially over the previous year, with half of new users being aged 45+ years. While use in older adults has been low historically, as those born in the 1950s and 1960s continue to age, this demographic will progressively have more liberal attitudes, prior cannabis exposure and higher use rates. However, older adults experience slower metabolism, increased likelihood of polypharmacy, cognitive decline and chronic physical/mental health problems. There is a need to enhance knowledge of the effects of cannabis use in older adults. The following question will be addressed using a scoping review approach: what evidence exists regarding beneficial and harmful effects of medical and non-medical cannabis use in adults >50 years of age? Given that beneficial and harmful effects of cannabis may be mediated by patient-level (eg, age, sex and race) and cannabis-related factors (eg, natural vs synthetic, consumption method), subgroup effects related to these and additional factors will be explored.Methods for scoping reviews outlined by Arksey & O'Malley and the Joanna Briggs Institute will be used. A librarian designed a systematic search of the literature from database inception to June 2019. Using the OVID platform, Ovid MEDLINE will be searched, including Epub Ahead of Print and In-Process and Other Non-Indexed Citations, Embase Classic+Embase, and PsycINFO for reviews, randomised trials, non-randomised trials and observational studies of cannabis use. The Cochrane Library on Wiley will also be searched. Eligibility criteria will be older adult participants, currently using cannabis (medical or non-medical), with studies required to report a cannabis-related health outcome to be eligible. Two reviewers will screen citations and full texts, with support from artificial intelligence. Two reviewers will chart data. Tables/graphics will be used to map evidence and identify evidence gaps.This research will enhance awareness of existing evidence addressing the health effects of medical and non-medical cannabis use in older adults. Findings will be disseminated through a peer-reviewed publication, conference presentations and a stakeholder meeting.DOI 10.17605/OSF.IO/5JTAQ.

This article describes the application of a recently proposed framework for deploying wastewater-based epidemiology (WBE) to monitor illicit drug use within festivals (Benaglia et al., 2019). The festival under study was a week-long music festival in Switzerland (Swiss Festival) which attracted around 50,000 people daily. Wastewater sampling was performed during its 2014 and 2015 editions. As the Swiss Festival's wastewater is conveyed to the sewage treatment plant (STP) of the nearby city, to assess illicit drug use when there is no festival (i.e. the background consumption) wastewater sampling was also carried out during an off-festival week in 2015. During the 2014 and 2015 editions of the Swiss Festival, WBE highlighted that the most consumed illicit drugs were cannabis, MDMA, cocaine and amphetamine. Excluding cannabis, the means per capita loads of all illicit drugs were not statistically different between both editions of the Swiss Festival. The results were then compared to those of an Australian festival which had also been subject of a quantitatively assessed illicit drug use study (Lai et al., 2013). This comparison confirmed that MDMA is highly prevalent, as well as amphetamine, although to a lesser extent. Consumption of cocaine (in Switzerland) and methamphetamine (in Australia) is also high, but their use seems to be related to their availability (i.e. to the country where the festival takes place). Furthermore, it was observed that MDMA and amphetamine are more consumed during the festival compared to normal times, when there is no festival. This might suggest that their availability is increased and therefore, that a market for these substances potentially exists during the festival. This last hypothesis was assessed by consulting drug seizures made by the police during the 2015 Swiss Festival. Despite very limited data, police records suggested that most of the drugs were purchased at the festival, which supports the previous hypothesis. Results validate, on the one hand, WBE as a useful indicator to monitor illicit drug use within festivals and on the other hand, the suggested framework for deploying WBE in such environment. In addition, this study suggests the need for prevention and harm reduction measures targeted on MDMA and amphetamine during the Swiss Festival, such as drug checking laboratories.

Olfactory detection of cannabis aroma by police officers can be the basis for warrantless searches of motor vehicles in many jurisdictions in the United States. The odor source in these cases is often dried cannabis flower contained in various casual wrappings as well as in more elaborate packaging. Here we investigate whether packaging format alters the detectability of the cannabis. Two cannabis strains and five packaging formats were evaluated. Untrained observers were presented with two containers and asked to identify, based only on smell, the container that held a sample of packaged cannabis (the other container held identical, but empty, packaging material). The results showed that open and casually packaged cannabis was identified with high accuracy, while material packaged in doubly vacuum-sealed plastic was correctly identified at rates no different from chance. The results may help address issues involving the detectability of cannabis aroma in law enforcement and other scenarios.

Acute and chronic exposure to cannabis and its main psychoactive component, 9-tetrahydrocannabinol (THC), is associated with changes in brain function and cerebral blood flow (CBF). We therefore sought to systematically review the literature on the effects of THC on CBF following PRISMA guidelines. Studies assessing the acute and chronic effects of THC on CBF, perfusion and volume were searched in the PubMed database between January 1972 and June 2019. We included thirty-four studies, which altogether investigated 1259 humans and 28 animals. Acute and chronic THC exposure have contrasting and regionally specific effects on CBF. While acute THC causes an overall increase in CBF in the anterior cingulate cortex, frontal cortex and insula, in a dose-dependent manner, chronic cannabis use results in an overall reduction in CBF, especially in the prefrontal cortex, which may be reversed upon prolonged abstinence from the drug. Future studies should focus on standardised methodology and longitudinal assessment to strengthen our understanding of the region-specific effects of THC on CBF and its clinical and functional significance.

Background: Cannabidiol (CBD), a non-psychoactive component of cannabis is marketed as a potential treatment for many conditions and widely available to purchase as a dietary supplement. In 2017, sales of CBD exceeded 820 million dollars despite many unconfirmed health claims, murky legality, and limited product efficacy and safety testing.Purpose/Objectives: This study aims to explore cannabidiol (CBD) knowledge, attitudes, and use among young adults.Methods: The anonymous 36-item survey developed using Qualtrics was distributed via social media from November 2018 to January 2019 with 340 respondents.Results: Of the 340 respondents, 242 reported they had heard of CBD, and 135 reported using CBD products. CBD users were primarily white, female, without children, made less than $25,000 per year, and unmarried. Most commonly used CBD products were edibles (56.30%), tinctures (54.07%), and vape (38.52%). Top reasons for use included stress relief (65.39%), relaxation (54.81%), and sleep improvement (42.22%). Many respondents reported using guesswork to determine dosage, and over half of respondents reported at least one unanticipated side effect.Conclusions/Importance: This study revealed that many users are not responsibly using CBD products, many believe CBD products provide health benefits that are not yet scientifically proven, and they are not knowledgeable about legal and regulatory issues. Until CBD use is more thoroughly researched and has more comprehensive regulation, public health professionals should address alternative stress and anxiety treatment methods.

CBD products have risen in popularity given CBD's therapeutic potential and lack of legal oversight, despite lacking conclusive scientific evidence for widespread over-the-counter usage for many of its perceived benefits. While medical evidence is being generated, social media surveillance offers a fast and inexpensive alternative to traditional surveys in ascertaining perceived therapeutic purposes and modes of consumption for CBD products.We collected all comments from the CBD subreddit posted between January 1 and April 30, 2019 as well as comments submitted to the FDA regarding regulation of cannabis-derived products and analyzed them using a rule-based language processing method. A relative ranking of popular therapeutic uses and product groups for CBD is obtained based on frequency of pattern matches including precise queries that entail identifying mentions of the condition, a CBD product, and some "trigger" phrase indicating therapeutic use. We validated the social media-based findings using a similar analysis on comments to the U.S. Food and Drug Administration's (FDA) 2019 request-for-comments on cannabis-derived products.CBD is mostly discussed as a remedy for anxiety disorders and pain and this is consistent across both comment sources. Of comments posted to the CBD subreddit during the monitored time span, 6.19% mentioned anxiety at least once with at least 6.02% of these comments specifically mentioning CBD as a treatment for anxiety (i.e., 0.37% of total comments). The most popular CBD product group is oil and tinctures.Social media surveillance of CBD usage has the potential to surface new therapeutic use-cases as they are posted. Contemporary social media data indicate, for example, that stress and nausea are frequently mentioned as therapeutic use cases for CBD without corresponding evidence, that affirms or denies, in the research literature. However, the abundance of anecdotal claims warrants serious scientific exploration moving forward. Meanwhile, as FDA ponders regulation, our effort demonstrates that social data offers a convenient affordance to surveil for CBD usage patterns in a way that is fast and inexpensive and can inform conventional electronic surveys.

Background: In Germany, cannabis is the most widely used illicit drug, and inhalation together with tobacco is most popular. However, it has been described that electronic cigarettes (ECs) are being used to vaporize cannabis (extract). No current data on EC cannabis use in the German population are yet available. Objectives: This study examines the prevalence of EC cannabis consumption for mood changing effects among current EC users, and associated consumer characteristics in Germany. Methods: We used data from the German Study on Tobacco Use (period: 8/2016-01/2019, DEBRA, www.debra-study.info), a nationally representative household survey. EC cannabis use for mood-changing effects was assessed in 504 current EC users (aged ≥ 18 years) of the total sample (N = 32,678). Ever use was defined by: (1) occasional or regular use, or (2) experimental consumption. Associations with socio-demographic consumer characteristics and tobacco smoking were analyzed using multivariable regression analyses. Results: Amongst current EC users, 7.2% had ever vaporized cannabis: 2.3% (95%CI = 1.2-3.9) reported occasional or regular use (1) and 4.8% (95%CI = 3.2-7.1) reported experimental use (2). Age was associated with ever EC cannabis use: highest prevalence rates were found among 18-24-year-olds: 6.5% (95%CI = 2.3-13.1) (1) and 8.0% (95%CI = 3.7-15.8) (2), respectively. The majority (90.2%) of ever EC cannabis users were current tobacco smokers. Conclusions: One in 14 current EC users in Germany has ever vaporized cannabis for mood-changing reasons, and almost all EC cannabis consumers also smoke tobacco. Highest usage rates can be observed among young adults. Hence, trends of EC drug misuse need to be monitored consequently, particularly in young people.

There is current controversy surrounding the long-term prescription of opioids to persistent pain (PP) pa-tients due to potential dangers of addiction and overdose. This study is the first to explore the perspectives of PP pa-tients attending a multidisciplinary pain clinic on the benefits associated with using opioids and other self-medication strategies for pain relief.Cross-sectional study utilizing a self-administered survey of patients attending an Austra-lian General Practice pain clinic for treatment of PP for at least 1 year (n = 93; response rate = 89 percent).Of the 93 participants, 79 percent reported being on opioid medication, with 49 percent on such medication for over 1 year. One or more side-effects were experienced by 53 percent of PP patients using opioids (although all felt these side-effects were at least "somewhat" acceptable). In addition, 64 percent of PP on opioid medication felt the benefits were "sub-stantially" worth the risk of harm, and 50 percent reported their medication had led to "substantial" improvements in their qual-ity of life. Many PP patients also used nonprescription medications and other complementary therapies for pain relief; how-ever, only the illicit drug cannabis was consistently stated (by 79 percent of users) to have benefits regarding relaxation and sleeping.Overall, PP patients felt the benefits of opioid use outweighed the risks, and using opioid medication sig-nificantly improved their quality of life. This may be partly due to the poor efficacy of other nonprescription medications and complementary therapies in managing PP beyond short-term relief.

Cannabis (marijuana) is one of the most consumed psychoactive substances in the world. The term marijuana is of Mexican origin. The primary cannabinoids that have been studied to date include cannabidiol and delta-9-tetrahydrocannabinol, which is responsible for most cannabis physical and psychotropic effects. Recently, the endocannabinoid system was discovered, which is made up of receptors, ligands and enzymes that are widely expressed in the brain and its periphery, where they act to maintain balance in several homeostatic processes. Exogenous cannabinoids or naturally-occurring phytocannabinoids interact with the endocannabinoid system. Marijuana must be processed in a laboratory to extract tetrahydrocannabinol and leave cannabidiol, which is the product that can be marketed. Some studies suggest cannabidiol has great potential for therapeutic use as an agent with antiepileptic, analgesic, anxiolytic, antipsychotic, anti-inflammatory and neuroprotective properties; however, the findings on cannabinoids efficacy and cannabis-based medications tolerability-safety for some conditions are inconsistent. More scientific evidence is required in order to generate recommendations on the use of medicinal cannabis.

To explore sociodemographic, psychological and psychopathological characteristics, as well as to evaluate the behaviour in an inmate sample.There is a total sample of 182 young and elderly inmates of the Madrid III Prison. The investigation has been carried out with a battery of self-report psychological questionnaires and objective measurements obtained through the prison files. Comparisons of means were made to see if there are significant differences between the two groups (young and elderly inmates) in the variables analysed.The analysis shows that there are no significant differences in wellbeing between young and elderly inmates. However, young people have higher levels of psychological distress, more presence of negative emotions and have a more maladjusted behaviour in prison (they consume more cannabis and have more disciplinary records). Older people better regulate their emotions, adopt better the perspectives of others, showing themselves to be friendlier.The elderly inmates in prison, compared with the youngest, have a better psychological adjustment, more internal resources and a better adaptation to the prison environment despite of no differences in related variables such as time in prison.

The Canadian government legalized non-medical cannabis use by adults in October 2018 in order to minimize associated harms and re-direct profits from criminals.Seven quarters of (NCS) data were combined into two groups: pre- and post-legalization periods - to examine changes in: cannabis use (overall, daily or almost daily (DAD)), source of product, driving after consumption and riding in a vehicle with a driver who had consumed.By 2019, overall cannabis use had increased (16.8% vs. 14.9%), particularly among: males, adults aged 25 and older, and in Newfoundland and Labrador, Nova Scotia, New Brunswick, and Alberta. DAD use, at 6.0%, remained stable, as did the prevalence of driving within 2 hours of consumption (13.2%). Riding in a vehicle with a driver who had used declined, overall (from 5.3% to 4.2%) and among: females, persons aged 25 and older, and in Newfoundland and Labrador, Ontario and Alberta. Where Canadians reported obtaining their cannabis also changed, with increasing percentages reporting getting some or all of their cannabis from legal sources, and fewer using illegal sources or relying on friends/family. Some provinces experienced more change than others.While too soon to observe the longer-term impacts associated with the Cannabis Act, early indications based on data collected in the months surrounding enactment suggests some cautions and also some assurances. Ongoing monitoring will be essential particularly given the 2.0 Act modifications and the ever-changing provincial retail and regulatory landscapes.

We report a case of transient ECG abnormalities (negative T waves in the inferior leads) associated with presyncope related to acute cannabis consumption; after a few hours the ECG returned normal. Although pathophysiological mechanisms are not clear, it might be hypothesize a mismatch between increased oxygen demand and decreased oxygen supply or a marked hyperactivation of the sympathetic nervous system.

Dementia is a neurological condition that affects the cognitive and functional ability of the brain and is the leading cause of disability among those aged 65 years and above. More effective ways to manage dementia symptoms are needed because current treatment options (antidepressants and antipsychotics) can be ineffective and are associated with substantial side effects, including increased rate of mortality. Cannabinoid-based medicine (CBM) has shown an ability to inhibit some symptoms associated with dementia, and the adverse effects are often minimal; yet, little research has explored the use of CBM among this population.To monitor the safety of a purified dose of CBM oil (3:2 delta-9-tetrahydrocannabinol:cannabidiol) on behaviour symptoms, quality of life and discomfort caused by pain.We will carry out an 18-week, randomised, double-blind crossover trial that consists of a 2-week eligibility period, two 6-week treatment cycles, and two 2-week washout periods (between both cycles and after the second treatment cycle). We aim to recruit 50 participants with dementia who are living in residential aged-care facilities. The participants will be randomised into two groups and will receive a dose of either CBM oil or placebo for the first treatment cycle and the opposite medication for the second. Data will be collected using the Neuropsychiatric Inventory Questionnaire, the Cohen-Mansfield Agitation Inventory, the Quality of Life in Alzheimer's Disease questionnaire, and the Abbey Pain Scale on seven occasions. These will be completed by the participants, aged-care staff, and nominated next of kin or family members. The participants' heart rate and blood pressure will be monitored weekly, and their body composition and weight will be monitored fortnightly by a research nurse, to assess individual dose response and frailty. In addition, pre- and post-surveys will be administered to aged-care staff and family members to understand their perceptions of CBM and to inform proposed focus groups consisting of the aged-care staff and next of kin.The study design has been informed by medical professionals and key stakeholders, including those working in the residential aged-care industry to ensure patient safety, collection of non-invasive measures, and methodological rigor and study feasibility.Australian New Zealand Clinical Trials Registry, ACTRN12619000474156. Registered on 21 March 2019.

Comorbidity between Substance Use Disorders (SUDs) and major depression is highly prevalent. This systematic review and meta-analysis aimed to estimate the prevalence of SUDs in subjects diagnosed with a major depressive disorder (MDD) in community, inpatient and outpatient settings.A comprehensive literature search of Medline, EMBASE, PsycINFO and CINAHL databases was conducted from 1990 to 2019. Prevalence of co-morbid SUDs and MDD were extracted and odds ratios (ORs) were calculated using random effects meta-analysis.There were 48 articles identified by electronic searches with a total sample size of 348,550 subjects that yielded 14 unique epidemiological studies, 2 national case registry studies, 7 large cohort studies and 20 clinical studies using in- or out-patients. The prevalence of any SUD in individuals with MDD was 0.250. Maximum prevalence was found with alcohol use disorder (0.208), followed by illicit drug use disorder (0.118) and cannabis use disorder (0.117). Meta-analysis showed the pooled variance of any AUD in men with MDD was 36%, which was significantly higher than that for females with MDD (19%, OR 2.628 95% CI 2.502, 2.760).Few studies were published over the last decade so current prevalence rates of SUD in MDD are needed. Meta-analysis revealed that SUDs in MDD are highly prevalent and rates have not changed over time. The persistently high prevalence suggests there is an urgent need for more informative studies to help develop better prevention and treatment options for reducing prevalence of SUDs in persons with major depression and co-morbid disorders.

Since 2004, the National Institute for Occupational Safety and Health (NIOSH) has received 10 cannabis-related health hazard evaluation (HHE) investigation requests from law enforcement agencies (n = 5), state-approved cannabis grow operations (n = 4), and a coroner's office (n = 1). Earlier requests concerned potential illicit drug exposures (including cannabis) during law enforcement activities and criminal investigations. Most recently HHE requests have involved state-approved grow operations with potential occupational exposures during commercial cannabis production for medicinal and non-medical (recreational) use. As of 2019, the United States Drug Enforcement Administration has banned cannabis as a Schedule I substance on the federal level. However, cannabis legalization at the state level has become more common in the USA. In two completed cannabis grow operation HHE investigations (two investigations are still ongoing as of 2019), potential dermal exposures were evaluated using two distinct surface wipe sample analytical methods. The first analyzed for delta-9-tetrahydrocannabinol (Δ9-THC) using a liquid chromatography and tandem mass spectrometry (LC-MS-MS) method with a limit of detection (LOD) of 4 nanograms (ng) per sample. A second method utilized high performance liquid chromatography with diode-array detection to analyze for four phytocannabinoids (Δ9-THC, Δ9-THC acid, cannabidiol, and cannabinol) with a LOD (2000 ng per sample) which, when comparing Δ9-THC limits, was orders of magnitude higher than the LC-MS-MS method. Surface wipe sampling results for both methods illustrated widespread contamination of all phytocannabinoids throughout the tested occupational environments, highlighting the need to consider THC form (Δ9-THC or Δ9-THC acid) as well as other biologically active phytocannabinoids in exposure assessments. In addition to potential cannabis-related dermal exposures, ergonomic stressors, and psychosocial issues, the studies found employees in cultivation, harvesting, and processing facilities could potentially be exposed to allergens and respiratory hazards through inhalation of organic dusts (including fungus, bacteria, and endotoxin) and volatile organic compounds (VOCs) such as diacetyl and 2,3-pentanedione. These hazards were most evident during the decarboxylation and grinding of dried cannabis material, where elevated job-specific concentrations of VOCs and endotoxin were generated. Additionally, utilization of contemporary gene sequencing methods in NIOSH HHEs provided a more comprehensive characterization of microbial communities sourced during cannabis cultivation and processing. Internal Transcribed Spacer region sequencing revealed over 200 fungal operational taxonomic units and breathing zone air samples were predominantly composed of Botrytis cinerea, a cannabis plant pathogen. B. cinerea, commonly known as gray mold within the industry, has been previously associated with hypersensitivity pneumonitis. This work elucidates new occupational hazards related to cannabis production and the evolving occupational safety and health landscape of an emerging industry, provides a summary of cannabis-related HHEs, and discusses critical lessons learned from these previous HHEs.

Introduction: Cannabis is the most widely used illicit drug in the US, and cannabis use among young adults continues to rise. Previous studies have shown that chronic administration of delta 9-tetrahydrocannabinol (THC), the main psychoactive component of cannabis, induces dependence in animal models. Because smoking is the most frequent route of THC self-administration, it is critical to investigate the effects of cannabis smoke inhalation. The goal of the current study was to develop a rat model to characterize the pharmacokinetics (PKs) of THC after cannabis smoke inhalation, and to determine if chronic cannabis smoke inhalation leads to the development of cannabis dependence. Materials and Methods: For the PK study, male Wistar rats were administered THC intravenously (1 mg/kg) or exposed to smoke from 5 or 10 sequentially smoked cannabis cigarettes (5.3% THC) in an automated smoking machine. Plasma samples were collected from 10 min to 10 hours post smoke exposure (or intravenous administration) and analyzed using liquid chromatography-mass spectrometry to characterize the PK of THC. A three-compartment PK model was used to characterize the PKs. In a separate study, three groups of male Wistar rats were trained in an intracranial self-stimulation (ICSS) procedure, and exposed to smoke from burning 5 or 10 cannabis cigarettes (or clean air control conditions), 5 days/week for 4 weeks. Discussion and Conclusions: Across exposure days, the change from baseline in ICSS thresholds for cannabis smoke-exposed groups was significantly lower and response latencies were significantly faster in the cannabis smoke-exposed groups compared to controls, suggesting that chronic cannabis smoke exposure has rewarding properties. Acute administration of the CB1 receptor antagonist rimonabant (0.3, 1.0, 3.0 mg/kg) induced a dose-dependent increase in ICSS thresholds in the smoke-exposed rats, suggestive of dependence and withdrawal. Finally, an effect compartment PK-pharmacodynamic model was used to describe the relationship between THC concentrations and changes in ICSS thresholds after cannabis smoke exposure.

The aim of our study was to perform a systematic review of the literature and meta-analysis in order to investigate relationship between drug use and oral health.We searched for studies in English published before July 1, 2019 on PsycINFO, PubMed, SciELO, Scopus, and Web of Science. We assessed the relationship between drug use (methamphetamines, heroin; opiates; crack, cocaine and cannabis as dependent variables) and reported tooth loss, periodontal disease, or decayed, missing, and filled teeth index as an independent variable. The data were analyzed using Stata 12.0 software.We initially identified 1836 potential articles (with 1100 duplicates) and screened the remaining 736 titles and abstracts, comprising 54 studies. In the next step, we evaluated the full-texts; 44 studies were excluded, accordingly. In total, we included 10 publications in the meta-analysis. Drug type was associated with periodontal disease (OR 1.44; 95% CI 0.8-2.6) and pooled estimates showed that type of drug used increased the odds of the number of decayed, missed and filled teeth (DMFT) (OR 4.11; 95% CI 2.07-8.15) respectively.The analytical challenges of segregating the impact of individual drug types on oral health diseases mean that investigations on the direct relationship between oral health status and drug use are limited. Developing programs to improve potential confounding with various substances and addressing the dental health needs of people who use drugs is vital if we are to improve their overall quality of life.

Observational data and preliminary studies suggest serotonin 2A agonist psychedelics may hold potential in treating a variety of substance use disorders (SUDs), including opioid use disorder (OUD).The study aim was to describe and analyze self-reported cases in which naturalistic psychedelic use was followed by cessation or reduction in other substance use.An anonymous online survey of individuals reporting cessation or reduction in cannabis, opioid, or stimulant use following psychedelic use in non-clinical settings.Four hundred forty-four respondents, mostly in the USA (67%) completed the survey. Participants reported 4.5 years of problematic substance use on average before the psychedelic experience to which they attributed a reduction in drug consumption, with 79% meeting retrospective criteria for severe SUD. Most reported taking a moderate or high dose of LSD (43%) or psilocybin-containing mushrooms (29%), followed by significant reduction in drug consumption. Before the psychedelic experience 96% met SUD criteria, whereas only 27% met SUD criteria afterward. Participants rated their psychedelic experience as highly meaningful and insightful, with 28% endorsing psychedelic-associated changes in life priorities or values as facilitating reduced substance misuse. Greater psychedelic dose, insight, mystical-type effects, and personal meaning of experiences were associated with greater reduction in drug consumption.While these cross-sectional and self-report methods cannot determine whether psychedelics caused changes in drug use, results suggest the potential that psychedelics cause reductions in problematic substance use, and support additional clinical research on psychedelic-assisted treatment for SUD.

The objective of this study is to assess the changes in rates of juvenile cannabis criminal allegations and racial disparities in Oregon after legalization of cannabis (July 2015) for adults.This study included all allegations for cannabis-related offenses that occurred from January 2012 to September 2018 in Oregon. Negative binomial regression models were used to examine monthly cannabis allegation rates over time, and tested differences between youth of color and white youth, adjusting for age, gender, and month the allegation occurred. Analysis was conducted in January-March 2019.Cannabis allegation rates increased 28% among all youth and 32% among cannabis-using youth after legalization. Rates of allegations were highest for American Indian/Alaska Native and black youth. Rates for black youth were double that of whites before legalization, and this disparity decreased after legalization. For American Indian/Alaska Native youth, rates were higher than whites before legalization, and this disparity remained unchanged.Adult cannabis legalization in Oregon was associated with increased juvenile cannabis allegations; increases are not explained by changes in underage cannabis use. Relative disparities decreased for black youth but remained unchanged for American Indian/Alaska Native youth. Changing regulations following adult cannabis legalization could have unintended negative impacts on youth.

Objective. To systematically assess previous findings on the orbitofrontal sulcogyral pattern in psychiatric disorders and to address the utility of this pattern as a transdiagnostic trait marker of early neurodevelopment in the social brain. Methods. An online literature search was conducted using the PubMed database from inception to August 2019. Studies included in this review were based on the Chiavaras's original classification method of this H-shaped sulcus (type I, II, and III), intermediate orbital sulcus (IOS), and posterior orbital sulcus (POS). Results. Twenty-six studies were included in the review. Sixteen studies (62%) focused on schizophrenia spectrum (Sz) disorders, and the remaining studies focused on autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), history of extremely preterm and extremely low birth weight, bipolar disorder (BD), panic disorder, obsessive-compulsive disorder, cannabis users, and pathological gambling. In Sz, compared with healthy controls, the orbitofrontal sulcogyral pattern was decreased in type I, increased in type II and III, and there were fewer numbers of IOS and POS reported, although specificity in sex and hemispheric dominance was not consistent. BD and neurodevelopmental disorders in ASD and ADHD showed a similar pattern of alteration to that observed in the Sz. Conclusions. The present review of the orbitofrontal sulcogyral pattern indicated that type I expression might reflect a neurodevelopmental protective marker, and type II and III expressions, as well as fewer numbers of IOS and POS, might reflect neurodevelopmental risk markers. These trait markers may be transdiagnostic among socially disabling diseases.

The TIP (Traumatic Injury Prevention) Project evaluated the impact on post-injury drug use of two brief motivational interventions compared to brief advice (BA) among injured patients who use drugs.Three-group, single blind, randomized controlled trial in a Level 1Trauma Center enrolled 395 admitted patients with drug positive toxicology screen or verbal report of drug use in the previous 30 days. 34% were Hispanic, 45% non-Hispanic White, 16% non-Hispanic Black. 88% smoked marijuana, 28% used cocaine and 11% prescription opioids. Brief Advice (BA) provided advice to abstain from drugs, educational materials and referral to community resources. Brief Motivational Intervention (BMI) additionally included a 30-45 minute session, with assessment feedback, based on motivational interviewing. BMI + B included a telephone booster 4-weeks post-intervention. Drug use as measured by percent days abstinent and total abstinence, derived from the Timeline Follow back was the primary outcome.A significant reduction from baseline was observed at 3, 6, and 12 months in the primary outcomes of any drug use (excluding alcohol); cannabis and cocaine, the most frequently used drugs, were analyzed individually. There were no between group differences or group X time interactions. Similarly, there were no between groups differences on secondary outcomes including perceived health status, re-injury, arrest, incarceration, alcohol and drug treatment, employment, AA attendance, homelessness, physical abuse, and problems associated with alcohol and drug use.The study does not support use of these enhanced motivational interventions over brief advice for trauma patients with a positive screen for drug use.

To describe marijuana's clinical role for urologic symptoms.Studies related to marijuana, voiding dysfunction, lower urinary tract symptoms (LUTS), and pain through January 2019 from PubMed were evaluated for relevance and quality.Forty-eight studies were reviewed. Cannabinoids have mixed efficacy for neurogenic LUTS and little evidence for non-neurogenic LUTS, chronic non-cancer-related and perioperative pain. For cancer-related pain, high-level studies demonstrate cannabinoids are well-tolerated with unclear benefit.Cannabinoids appear well-tolerated in the short-term, but their efficacy and long-term impact is unproven and unknown in urologic discomfort. Cannabinoids for urologic symptoms should be further explored with well-designed RCTs.

(©Zehra A, Liuck, Manza P, Wiers CE, Volkow ND Wergh J, 2018. Reprinted with permission from Journal of Neuroimmune Pharmacology (2018) 13:438-452).

(Reprinted with permission from Sabioni P and Le Foll B. Psychosocial and pharmacological interventions for the treatment of cannabis use disorder [version 1; referees: 3 approved]. F1000Research 2018, 7(F1000 Faculty Rev):173 (https://doi.org/10.12688/f1000research.11191.1)).

An online questionnaire.To assess the international spinal cord medicine and rehabilitation community's utilization of pharmacological and non-pharmacological treatments for spinal cord damage (SCD)-related pain and to determine whether approaches to SCD-related pain differ between developed and less developed nations.An international collaboration of authors.An on-line survey querying availability and utilization of a number of approaches to SCD-related pain was developed, distributed, and made available for 6 months. Responses were analyzed for the entire cohort and according to participants' descriptions of their home nations' economies.A total of 153 responses were submitted, mostly from developed nations. Nearly three quarters of subjects reported offering their patients with SCD narcotics; only 13% reported offering their patients with SCD medical cannabis. Subjects from developing countries were more likely than those from developed countries to prescribe buprenorphine (20.0% vs 15.6%; p = 0.001) and less likely to prescribe medical cannabis (0% vs 15.6%; p = 0.001) and acupuncture (4.0% vs 23.4%; p = 0.02).Most spinal cord medicine clinicians employ a multimodal approach to pain. There are significant differences in utilization of pharmacologic and non-pharmacologic approach to SCD-related pain between clinicians from more and less developed countries.

Gene copy number (CN) variation is known to be important in nearly every species where it has been examined. Alterations in gene CN may provide a fast way of acquiring diversity, allowing rapid adaptation under strong selective pressures, and may also be a key component of standing genetic variation within species. Cannabis sativa plants produce a distinguishing set of secondary metabolites, the cannabinoids, many of which have medicinal utility. Two major cannabinoids-THCA (delta-9-tetrahydrocannabinolic acid) and CBDA (cannabidiolic acid)-are products of a three-step biochemical pathway. Using whole-genome shotgun sequence data for 69 Cannabis cultivars from diverse lineages within the species, we found that genes encoding the synthases in this pathway vary in CN. Transcriptome sequence data show that the cannabinoid paralogs are differentially expressed among lineages within the species. We also found that CN partially explains variation in cannabinoid content levels among Cannabis plants. Our results demonstrate that biosynthetic genes found at multiple points in the pathway could be useful for breeding purposes, and suggest that natural and artificial selection have shaped CN variation. Truncations in specific paralogs are associated with lack of production of particular cannabinoids, showing how phytochemical diversity can evolve through a complex combination of processes.

Polysubstance use (PSU) is highly prevalent among college students. Recent evidence indicates that PSU is based on gene x environment (G×E) interactions, yet the specific biosocial factors underlying this problem remain elusive. We recently reported that lifetime use of tobacco and cannabis in college students is influenced by the interaction of the X-linked MAOA (monoamine oxidase A) gene and child maltreatment. Building on these premises, here we evaluated whether the same G×E interaction may also predict PSU in this population. Students of a large Midwestern university (n = 470; 50.9% females) took part in a computer survey for substance use, as well as childhood trauma exposure, using the Child Trauma Questionnaire (CTQ). DNA was extracted from their saliva samples and genotyped for MAOA variable-number of tandem repeat (VNTR) variants. Findings indicated that the highest number of substances were used by male students harboring low-activity MAOA alleles with a history of childhood emotional abuse. In contrast, female homozygous high-activity MAOA carriers with a history of emotional and physical abuse reported consumption of the greatest number of substances. Our results indicate that PSU among college students is influenced by the interaction of MAOA and child maltreatment in a sex-specific fashion. Further studies are warranted to understand the mechanisms of sex differences in the biosocial interplays underlying PSU in this at-risk group.

Can cannabis consumption alter sperm nuclear integrity in infertile men?A retrospective cross-sectional study conducted between July 2003 and December 2013, which included 54 men who consulted for male-factor infertility. Twenty-seven infertile men who were regular cannabis users were matched to 27 infertile men who were cannabis non-users. To complement the conventional semen parameter and plasma hormone level assessments, sperm nuclear alterations were explored using fluorescence in-situ hybridization to assess numerical chromosomal abnormalities, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling to investigate DNA fragmentation, aniline blue staining to examine chromatin condensation and a motile sperm organelle morphology examination to detect vacuoles in sperm heads.The rates of sperm aneuploidy (P = 0.0044), diploidy (P = 0.037), total chromosome abnormalities (P = 0.0027) and DNA fragmentation (P = 0.027) were significantly higher in cannabis users than in non-cannabis users.Cannabis consumption might have deleterious effects on sperm nuclear quality in infertile men by increasing numerical chromosome abnormalities and DNA fragmentation. Cannabis consumption induces these detrimental effects on the progression of spermatogenesis from meiotic stages to spermiogenesis and potentially on post-testicular sperm maturation in infertile men. Any potential findings, however, need to be validated with larger sample size, and our data are only exploratory findings.

Background: The intrinsic motivation behind the "need to complete" is more influential than external incentives. We introduced a novel progress-bar tool to motivate the completion of programs designed to treat stimulant and cannabis use disorders. We further examined the effectiveness of the progress bar's scoring approach in forecasting consistently negative urine tests. Methods: This study's participants included 568 patients with stimulant, amphetamine-type, and cannabis use disorders who were undergoing 12-month mandatory treatment programs at Taichung Veterans General Hospital in Taiwan. Patients were given scores of 1, -1, or 0 depending on whether they received negative, positive, or missing urinalysis reports, respectively. The autonomic progress bar generated weekly score totals. At the group level, scorei donated scores from all patients for a given week (i denoted the week). Scorei was standardized to adjusted scorei. We then conducted Autoregressive Integrated Moving Average (ARIMA) Model of time-series analyses for the adjusted scorei. Results: A total of 312 patients maintained treatment progress over the 12-month program. The autonomic score calculator totaled the shared achievements of these patients. The coefficients of the lag variables for mean (p), lag variables for residual error term (q), and number of orders for ensuring stationary (d) were estimated at p = 3, d = 4, and q = 7 for the first half of the treatment program, and were estimated at p = 2, d = 2, and q = 3 for the second half. Both models were stationary and tested as fit for prediction (p < 0.05). Sharply raised adjusted scores were predicted during the high-demand treatment phase. Discussion: This study's novel progress-bar tool effectively motivated treatment completion. It was also effective in forecasting continually negative urine tests. The tool's free open-source code makes it easy to implement among many substance-treatment services.

Background: Substance Use Disorder (SUD) and behavioral addictions are common and require a multidisciplinary approach. New technologies like Virtual Reality could have the potential to improve assessment and treatment of these disorders. Objective: In the present paper, we therefore present an overview of Virtual Reality (Head Mounted Devices) in the field of addiction medicine for craving assessment and treatment. Method: We conducted a systematic review by querying PubMed database for the titles of articles published up to March 2019 with the terms [virtual] AND [addictive] OR [addiction] OR [substance] OR [alcohol] OR [cocaine] OR [cannabis] OR [opioid] OR [tobacco] OR [nicotine] OR [methamphetamine] OR [gaming] OR [gambling]. Results: We screened 319 abstracts and analyzed 37 articles, dividing them into two categories, the first for assessment of cue reactivity (craving, psychophysiological response and attention to cue) and the second for intervention, each drug (nicotine, cocaine, alcohol, cannabis, gambling) being detailed within each category. Conclusions: This overview suggest that VR provide benefits in the assessment and treatment of substance use disorders and behavior addictions and achieve high levels of ecological validity. While, craving provocation in VR is effective across addiction disorders, treatments based exclusively on virtual exposure to drug related cues as shown heterogenous results.

Opiates are the second most prevalent abused illicit substance after cannabis in the world. The latest United Nations Office on Drugs and Crime (UNODC) report estimated 30% increment in opium cultivation worldwide. High prevalence of opium consumption in eastern countries may be due to the high availability and traditional misconceptions. Opium consumption has been linked to hypertension, diabetes mellitus, dyslipidemia, and coronary artery diseases (CAD). In this review, we will review the association between opium use, cardiovascular diseases, and clinical outcomes. The present evidence suggests that chronic opiate consumption may increase the risk of cardiovascular diseases and related mortality.

Background and aims Cannabinoids are increasingly used for medicinal purposes, including neuropathy. Gastroparesis is a neuromuscular disorder and neuropathy plays a large role in its pathogenesis. It is thus reasonable that cannabinoids can serve a beneficial role in the management of gastroparesis. Our study evaluates the effect of cannabinoids on gastroparesis symptoms. Methods Twenty-four (n=24) patients with gastroparesis and refractory symptoms were selected from a single gastroenterology practice associated with a tertiary care medical center. The 'Gastroparesis Cardinal Symptom Index' (GCSI) and an analog scale rating abdominal pain were applied to prospectively assess the effect of cannabinoids, in the form of dronabinol and medical cannabis, on refractory gastroparesis symptoms. Patients completed a GCSI form and rated their abdominal pain, before and after treatment. There was a minimum of 60 days of cannabinoid use between reporting intervals. Total composite GCSI symptom scores, GCSI symptom subset scores, and abdominal pain scores were calculated before and after treatment. Results A significant improvement in the GCSI total symptom composite score was seen with either cannabinoid treatment (mean score difference of 12.8, 95% confidence interval 10.4-15.2; p-value < 0. 001). Patients prescribed marijuana experienced a statistically significant improvement in every GCSI symptom subgroup. Significant improvement in abdominal pain score was also seen with either cannabinoid treatment (mean score difference of 1.6; p-value <0.001). Conclusions Cannabinoids dramatically improve the symptoms of gastroparesis. Furthermore, an improvement in abdominal pain with cannabinoids represents a breakthrough for gastroparesis-associated abdominal pain treatment, for which there are currently no validated therapies.

Beginning in June of 2019, there was a marked increase in reported cases of serious pulmonary injury associated with vaping. The condition, referred to as e-cigarette or vaping product use-associated lung injury (EVALI), does not appear to involve an infectious agent; rather, a chemical adulterant or contaminant in vaping fluids is suspected. In August of 2019, the Wadsworth Center began receiving vaporizer cartridges recovered from patients with EVALI for analysis. Having no a priori information of what might be in the cartridges, we employed untargeted analyses using gas chromatography-mass spectrometry and high-resolution mass spectrometry to identify components of concern. Additionally, we employed targeted analyses used for New York medical marijuana products. Here, we report on the analyses of 38 samples from the first 10 New York cases of EVALI for which we obtained cartridges. The illicit fluids had relatively low cannabinoid content, sometimes with unusual Δ9-/Δ8-tetrahydrocannabinol ratios, sometimes containing pesticides and many containing diluents. A notable diluent was α-tocopheryl acetate (vitamin E acetate; VEA), which was found in 64% of the cannabinoid-containing fluids. To investigate potential sources of the VEA, we analyzed six commercial cannabis-oil diluents/thickeners. Three were found to be >95% VEA, two were found to be primarily squalane, and one was primarily α-bisabolol. The cause(s) of EVALI is unknown. VEA and squalane are components of some personal care products; however, there is growing concern that vaping large amounts of these compounds is not safe.

To assess medical student knowledge, attitudes and beliefs about cannabis use for medical conditions in Russia where it is prohibited.This study uses data collected from 463 Russian origin medical students. Pearson Chi-square test for categorical variables was used to determine whether student knowledge, attitudes and beliefs of medical cannabis (MC) are affected by gender and religiosity.Overall, Russian university medical students tend to reflect negative attitudes and beliefs toward MC. Female students were more inclined to recommend MC for patient treatment and its legalization; and, believe it is not addictive and does not pose physical or mental health risk. Students who support MC use believe it has treatment benefits, support additional research as well as policy change for its legalization. Secular, more than religious, students report more positive attitudes toward MC use. About 34% of the students indicate they have no knowledge about cannabis use for medical conditions; and, nearly half report feel they are able to answer patient questions about its use for medical condition if such a situation were to exist.This study is the first in Russia to examine medical students' knowledge, attitudes and beliefs toward MC. Results evidence the majority of survey respondents do not support cannabis legalization for any purpose - medical or recreational. They report a dearth of knowledge about the substance and recommend additional evidence-based research and education to enhance their knowledge about its use. The present study has value in terms of providing usable information for possible curriculum development and education purposes as well as policy change about cannabis use for medical conditions in Russia.

Irritable bowel syndrome (IBS) global burden is underestimated despite its high prevalence. It's a gastrointestinal disease having obscure pathophysiology with multiple therapies yet unsatisfactory remedies. The Endocannabinoid system (ECS) of our body plays a key role in maintaining normal physiology of the gastrointestinal tract as well as involves abnormalities including functional diseases like IBS. This review highlights the importance of the Endocannabinoid system, its connections with the normal gastrointestinal functions and abnormalities like IBS. It also discusses the role of cannabis as medical therapy in IBS patients. A literature search for articles related to endocannabinoids in IBS and medical cannabis in PubMed and Google Scholar was conducted. The studies highlighted the significant participation of ECS in IBS. However, the breach in obtaining the promising therapeutic model for IBS needed further investigation in ECS and uncover other treatments for IBS. This review summarizes ECS, highlights the relationship of ECS with IBS and explores cannabis as a potential therapy to treat IBS.

Pain of a moderate or severe intensity affects over half of patients with advanced cancer and remains undertreated in at least one-third of these patients.The aim of this study was to provide a pragmatic overview of the evidence supporting the use of interventions in pain management in advanced cancer and to identify where encouraging preliminary results are demonstrated but further research is required.A scoping review approach was used to examine the evidence supporting the use of guideline-recommended interventions in pain management practice.National or international guidelines were selected if they described pain management in adult cancer patients and were written within the last 5 years in English. The Cochrane Database of Systematic Reviews (January 2014 to January 2019) was searched for 'cancer' AND 'pain' in the title, abstract or keywords. A MEDLINE search was also made.A strong opioid remains the drug of choice for treating moderate or severe pain. Bisphosphonates and radiotherapy are also effective for cancer-related bone pain. Optimal management requires a tailored approach, support for self-management and review of treatment outcomes. There is likely a role for non-pharmacological approaches. Paracetamol should not be used in patients taking a strong opioid to treat pain. Cannabis-based medicines are not recommended. Weak opioids, ketamine and lidocaine are indicated in specific situations only.Interventions commonly recommended by guidelines are not always supported by a robust evidence base. Research is required to evaluate the efficacy of non-steroidal anti-inflammatory drugs, anti-convulsants, anti-depressants, corticosteroids, some invasive anaesthetic techniques, complementary therapies and transcutaneous electrical nerve stimulation.

While a diverse array of cannabis products that may appeal to youth is currently available, it is unknown whether the risk of persistent cannabis use and progression to higher frequency of use after experimentation differs among cannabis products.To estimate the comparative relative risk of experimental use of 5 cannabis products on use status and frequency of use among adolescents during 12 months of follow-up.In this cohort study, data were collected from 3065 adolescents at 10 high schools in southern California, with baseline data collected in spring 2016, when students were in 11th grade, and 6-month and 12-month follow-up surveys collected in fall 2016 and spring 2017, when students were in 12th grade. Analyses, conducted from April to June 2019, were restricted to 2685 participants who were light or nonusers of any cannabis product (ie, ≤2 days in the past 30 days) at baseline.Number of days of use of each cannabis product (ie, combustible, blunts, vaporized, edible, or concentrated) in the past 30 days at baseline (ie, 1-2 vs 0 days).Past 6-month use (ie, yes vs no) and number of days of use in the past 30 days at 6-month and 12-month follow-ups for each product.Of 2685 individuals in the analytic sample, 1477 (55.0%) were young women, the mean (SD) age was 17.1 (0.4) years, and a plurality (1231 [46.6%]) were Hispanic individuals. Among them, 158 (5.9%) reported combustible cannabis use on 1 to 2 days of the past 30 days at baseline, 90 (3.4%) reported blunt use, 78 (2.9%) reported edible cannabis use, 17 (0.6%) reported vaping cannabis, and 15 (0.6%) reported using cannabis concentrates. In regression models adjusting for demographic characteristics and poly-cannabis product use, statistically stronger associations of baseline use with subsequent past 6-month use at the 6-month and 12-month follow-ups were observed for combustible cannabis use (odds ratio, 6.01; 95% CI, 3.66-9.85) and cannabis concentrate use (odds ratio, 5.87; 95% CI, 1.18-23.80) compared with use of blunts (OR, 2.77; 95% CI, 1.45-5.29) or edible cannabis (OR, 3.32; 95% CI, 1.86-5.95) (P for comparison < .05); vaporized cannabis use (OR, 5.34; 95% CI, 1.51-11.20) was not significantly different from the other products. In similarly adjusted models, we found the association of cannabis use at baseline with mean days of use at the 6-month and 12-month follow-ups was significantly stronger for cannabis concentrate than for other cannabis products; participants who had used cannabis concentrate on 1 to 2 of the past 30 days at baseline (vs 0 days) used cannabis concentrate a mean of 9.42 (95% CI, 2.02-35.50) more days in the past 30 days at the 6-month and 12-month follow-ups (P for comparison < .05).Cannabis control efforts should consider targeting specific cannabis products, including combustible cannabis and cannabis concentrate, for maximum public health consequences.

Contingency management is one of the most efficacious interventions to promote drug abstinence. Contingency management has traditionally been delivered in person so that clinicians could confirm drug abstinence and provide access to additional therapeutic services. Now, new technologies not only permit remote confirmation of abstinence, but also remote delivery of incentives. We discuss several technology-based tools to assess substance use, and new ways to deliver contingency management to promote tobacco, alcohol, and cannabis abstinence. These new tools have the potential to dramatically increase access while maintaining high levels of treatment fidelity. Technology-based methods also allow arranging group contingencies that harness online communities, and they permit targeting multiple health-risk behaviors with a combination of sensor-based technologies. Overall, there are unprecedented opportunities to link technology with contingency management to promote drug abstinence.

U.S. college campuses have witnessed a national increase of cannabis, stimulant, and illicit drug use among students over the past decade. Substance use among college students is associated with numerous negative outcomes including lower academic performance, a higher probability of unemployment after graduation, and an increased risk of committing and experiencing sexual assault. Several risk factors for substance use are specific to this population, including an affiliation with Greek life, perception of high academic pressure, and peer pressure. Students with problematic substance use also face unique challenges in planning treatment, including aspects of confidentiality, financial constraints, and potential university oversight and involvement. This article highlights the prevalence of substance use on college campuses and describes some of the specific challenges and approaches to treatment in this population, including screening tests and interventions for specific substances used on college campuses and evidence-based substance use programming for college students.

Although the opioid epidemic may command more national headlines, the past two decades have seen a revolution in cannabis policy driven largely by the public and by business interests. As a result, the population of cannabis users nationwide-especially of heavy users-has grown yearly. Although less visible than patients admitted to the emergency department for opioid-related overdose or to treatment for opioid use disorder, an estimated 4.5-7 million individuals in the United States are thought to meet criteria for cannabis use disorder in a given year. This article focuses on the developmental pathways of cannabis use disorder, the epidemiology of cannabis use among adolescents and adults in the context of rapidly changing state laws, and evidence-based treatment for the general psychiatrist. The authors provide an overview of pharmacological and psychosocial behavioral treatments for patients with the disorder while emphasizing aspects of clinical management unique to this patient population.

Studies have shown that cannabis can interfere with hematological parameters and platelet morphology. The purpose of this study is to investigate whether patients with cannabis use disorder undergoing primary total knee arthroplasty (TKA) have higher rates of (1) venous thromboemboli (VTEs); (2) readmissions; and (3) costs.Study group patients undergoing primary TKA were identified from a large, nationwide database. Patients who had a history of VTEs, deep vein thromboses (DVTs), pulmonary emboli (PEs), and coagulopathies before their TKA were excluded. Study group patients were matched to controls in a 1:4 ratio by age, sex, a comorbidity index, and medical comorbidities. The query yielded 18,388 patients (cannabis = 3680; controls = 14,708). Outcomes analyzed included rates of 90-day VTEs, DVTs, and PEs, in addition to 90-day readmissions and costs. A P value less than .01 was considered statistically significant.Patients who have cannabis use disorder were found to have significantly higher incidence and odds (2.79% vs 1.78%; odds ratio [OR], 1.58; P < .0001) of VTEs, DVTs (2.41% vs 1.44%; OR, 1.68; P < .0001), and PEs (0.97% vs 0.62%; P = .01). Readmissions were significantly higher (27.03% vs 23.18%; OR, 1.22; P < .0001) in patients who have cannabis use disorder. Patients with cannabis use disorder have significantly higher day of surgery ($14,024.88 vs $12,127.49; P < .0001) and 90-day costs ($19,155.45 vs $16,315.00; P < .0001).This study found that patients who have a cannabis use disorder have higher rates of thromboembolic complications, readmission rates, and costs following primary TKA compared to a matched cohort.

Long-term cannabis users manifest deficits in dopaminergic functions, reflecting Δ9-tetrahydrocannabinol (THC)-induced neuroadaptive dysfunctional dopamine signaling, similar to those observed upon dopamine D1-D2 heteromer activation. The molecular mechanisms remain largely unknown. We show evolutionary and regional differences in D1-D2 heteromer abundance in mammalian striatum. Importantly, chronic THC increased the number of D1-D2 heteromer-expressing neurons, and the number of heteromers within individual neurons in adult monkey striatum. The majority of these neurons displayed a phenotype co-expressing the characteristic markers of both striatonigral and striatopallidal neurons. Furthermore, THC increased D1-D2-linked calcium signaling markers (pCaMKIIα, pThr75-DARPP-32, BDNF/pTrkB) and inhibited cyclic AMP signaling (pThr34-DARPP-32, pERK1/2, pS845-GluA1, pGSK3). Cannabidiol attenuated most but not all of these THC-induced neuroadaptations. Targeted pathway analyses linked these changes to neurological and psychological disorders. These data underline the importance of the D1-D2 receptor heteromer in cannabis use-related disorders, with THC-induced changes likely responsible for the reported adverse effects observed in heavy long-term users.

This study was to discuss the research trend of dementia treatment using cannabis for the purpose of providing the basis of cannabis use for medical purposes in the future.This study searched publications, which were registered to databases or published by Aug 22, 2019, and targeted the full-text or abstracts of these publications. We selected the final nine studies met all selection criteria.These results implied that the CBD components of cannabis might be useful to treat and prevent AD because CBD components could suppress the main causal factors of AD. Moreover, it was suggested that using CBD and THC together could be more useful than using CBD or THC alone.We hope that there will be a solid foundation to use cannabis for medical use by continuously evaluating the possibility of using cannabis for clinical purposes as a dementia treatment substance and cannabis can be used as a positive tool.

Osteoarticular equine disease is a common cause of malady; in general, its therapy is supported on steroids and nonsteroidal anti-inflammatories. Nevertheless, many side effects may develop when these drugs are administered. Nowadays, the use of new alternatives for this pathology attention is demanded; in that sense, cannabinoid CB2 agonists may represent a novel alternative. Cannabinoid belongs to a group of molecules known by their psychoactive properties; they are synthetized by the Cannabis sativa plant, better known as marijuana. The aim of this study was to contribute to understand the pharmacology of cannabinoid CB2 receptors and its potential utilization on equine veterinary patients with a chronic degenerative painful condition. In animals, two main receptors for cannabinoids are recognized, the cannabinoid receptor type 1 and the cannabinoid receptor type 2. Once they are activated, both receptors exert a wide range of physiological responses, as nociception modulation. Recently, it has been proposed the use of synthetic cannabinoid type 2 receptor agonists; those receptors looks to confer antinociceptive properties but without the undesired psychoactive side effects; for that reason, veterinary patients, whit chronical degenerative diseases as osteoarthritis may alleviate one of the most common symptom, the pain, which in some cases for several reasons, as patient individualities, or side effects produced for more conventional treatments cannot be attended in the best way.

While a range of sources exist for marijuana users to acquire marijuana for medical or personal use, prior research on marijuana sources primarily focused on single sources. In this analysis, we longitudinally examined characteristics of multiple sources selected by marijuana users, motivations to use sources, and how a blend of marijuana sources accommodated users' needs. Young adult marijuana users (n=60) in Los Angeles, CA, where marijuana has been legal for medical use since 1996, completed two annual qualitative interviews on marijuana use practices and sources between 2014 and 2016. Approximately two-thirds were medical marijuana patients and one-third were non-patient users. Participants reported acquiring marijuana from the following primary sources across two interviews: dispensaries and delivery services, private sellers in the illicit market, friends and family, and marijuana events/conferences. While patients with legal medical access to marijuana typically purchased marijuana from dispensaries or delivery services, they often supplemented from other illicit sources. Non-patients often accessed marijuana through dispensary diversion but also other sources. As patients became non-patients and vice versa during the study period, source type changed too. Broad access to marijuana via legal and illicit sources in this sample is indicative of societal trends towards normalization of marijuana use.

Medicinal cannabis has received increased research attention over recent years due to loosening global regulatory changes. Medicinal cannabis has been reported to have potential efficacy in reducing pain, muscle spasticity, chemotherapy-induced nausea and vomiting, and intractable childhood epilepsy. Yet its potential application in the field of psychiatry is lesser known.The first clinically-focused systematic review on the emerging medical application of cannabis across all major psychiatric disorders was conducted. Current evidence regarding whole plant formulations and plant-derived cannabinoid isolates in mood, anxiety, sleep, psychotic disorders and attention deficit/hyperactivity disorder (ADHD) is discussed; while also detailing clinical prescription considerations (including pharmacogenomics), occupational and public health elements, and future research recommendations. The systematic review of the literature was conducted during 2019, assessing the data from all case studies and clinical trials involving medicinal cannabis or plant-derived isolates for all major psychiatric disorders (neurological conditions and pain were omitted).The present evidence in the emerging field of cannabinoid therapeutics in psychiatry is nascent, and thereby it is currently premature to recommend cannabinoid-based interventions. Isolated positive studies have, however, revealed tentative support for cannabinoids (namely cannabidiol; CBD) for reducing social anxiety; with mixed (mainly positive) evidence for adjunctive use in schizophrenia. Case studies suggest that medicinal cannabis may be beneficial for improving sleep and post-traumatic stress disorder, however evidence is currently weak. Preliminary research findings indicate no benefit for depression from high delta-9 tetrahydrocannabinol (THC) therapeutics, or for CBD in mania. One isolated study indicates some potential efficacy for an oral cannabinoid/terpene combination in ADHD. Clinical prescriptive consideration involves caution in the use of high-THC formulations (avoidance in youth, and in people with anxiety or psychotic disorders), gradual titration, regular assessment, and caution in cardiovascular and respiratory disorders, pregnancy and breast-feeding.There is currently encouraging, albeit embryonic, evidence for medicinal cannabis in the treatment of a range of psychiatric disorders. Supportive findings are emerging for some key isolates, however, clinicians need to be mindful of a range of prescriptive and occupational safety considerations, especially if initiating higher dose THC formulas.

To analyse how the New Zealand news media has reported on chronic pain and identify whether this publicly available information is reflective of best practice.A content analysis of news media published between January 2015 and June 2019, with a primary focus on chronic pain was undertaken. The Factiva, EBSCO and ProQuest databases, alongside popular New Zealand news websites were searched.Two hundred and forty news articles were included; the overarching themes identified in content analysis were (1) the lived experience and the impact of chronic pain (n=119/240), (2) pain management strategies with information on pharmacological (ie, opioids and medicinal cannabis) (n=107/240) and non-pharmacological strategies (eg) psychological therapies (36/240), physical activity (34/240), pain education (34/240), (3) the systemic issues influencing chronic pain healthcare pathways (n=79/240).Living with chronic pain is predominantly represented as a struggle, with a lesser focus on the ability to successfully self-manage and live a meaningful life. The limited emphasis on each of the non-pharmacological strategies suggest that the reports failed to communicate that these strategies should be a key component of self-managing chronic pain. New Zealand healthcare providers and researchers can collaboratively work with the media to provide evidence-based information on both non-pharmacological and pharmacological pain management strategies.

Cannabis sativa L. is an ancient medicinal plant wherefrom over 120 cannabinoids are extracted. In the past two decades, there has been increasing interest in the therapeutic potential of cannabis-based treatments for neurological disorders such as epilepsy, and there is now evidence for the medical use of cannabis and its effectiveness for a wide range of diseases. Cannabinoid treatments for pain and spasticity in patients with multiple sclerosis (Nabiximols) have been approved in several countries. Cannabidiol (CBD), in contrast to tetra-hydro-cannabidiol (THC), is not a controlled substance in the European Union, and over the years there has been increasing use of CBD-enriched extracts and pure CBD for seizure disorders, particularly in children. No analytical controls are mandatory for CBD-based products and a pronounced variability in CBD concentrations in commercialized CBD oil preparations has been identified. Randomized controlled trials of plant-derived CBD for treatment of Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS) have provided evidence of anti-seizure effects, and in June 2018, CBD was approved by the Food and Drug Administration as an add-on antiepileptic drug for patients two years of age and older with LGS or DS. Medical cannabis, with various ratios of CBD and THC and in different galenic preparations, is licensed in many European countries for several indications, and in July 2019, the European Medicines Agency also granted marketing authorisation for CBD in association with clobazam, for the treatment of seizures associated with LGS or DS. The purpose of this article is to review the availability of cannabis-based products and cannabinoid-based medicines, together with current regulations regarding indications in Europe (as of July 2019). The lack of approval by the central agencies, as well as social and political influences, have led to significant variation in usage between countries.

Neurofibromatosis type 1 (NF1) is a common genetic disorder. Pain is a major symptom of this disease which can be secondary to the development of plexiform and subcutaneous neurofibromas, musculoskeletal symptoms (such as scoliosis and pseudoarthrosis), and headaches. Visible neurofibromas add significant psychosocial distress for NF1 patients. Along with the chronic pain, psychosocial distress contributes to associated mood disorders, such as depression and anxiety. Cannabis has been the focus of many studies for treating multiple conditions, including epilepsy, multiple sclerosis, Parkinsonism disease, and many chronic pain conditions. Cannabidiol (CBD) is the major non-psychotropic component of cannabis. CBD has shown anti-inflammatory and analgesic properties, as well as having mood stabilizer and anxiolytic effects. In this report, we present the use of cannabidiol (CBD) for the management of chronic pain and concomitant mood disorder in an NF1 patient.

Health professional students frequently use alcohol and narcotics. The potential impact on academic performance and professional behaviour is concerning.This study aimed to determine self-reported use of alcohol, illicit substances (e.g. cannabis, lysergic acid diethylamide [LSD], magic mushroom, cocaine, crack, ecstasy, methamphetamine and heroin), prescription medication and smoking habits, correlating academic performance.Faculty of Health Sciences, University of the Free State.An observational, descriptive, cross-sectional study design was used. Information was obtained using a self-administered questionnaire, capturing demographics, self-reported academic performance, drinking and smoking habits, and substance use. Coded responses were analysed using the Remark Office OMR 8 Software System. Descriptive statistics were calculated for categorical variables.Completed questionnaires comprised 171 students. A total of 78.4% of second year and 82.8% of third year students reported using alcohol. Twenty-two per cent of second year and 24.1% of third year students reported cannabis use. In the second year group, three (2.7%) students reported using magic mushroom, two (1.8%) reported cocaine, two (1.8%) reported ecstasy and one (0.9%) reported using methamphetamine. Only third year students reported using LSD or 'crack'. Cigarette smoking was common - 31.5% and 35.1% in both groups, respectively. Smokeless tobacco devices were used by 8.5% of second year and 7.1% of third year students. Almost 40% of both groups reported that they had smoked a water pipe. Academic performance achieved was mostly 60% - 69% (38.9%) among second year students and 70% - 79% (46.6%) among third year students.Self-reported use of alcohol and drugs and smoking among medical students is alarming. Additional student support, early identification and referral for management and/or rehabilitation should be a priority at tertiary institutions responsible for training future healthcare professionals.

Recent analyses of data from the US found that young people were increasingly engaging in cannabis use before alcohol and cigarettes. These shifts are important for public health, but it is not clear whether such trends extend beyond the US. The aim of this study is to examine whether and how the age and sequencing of initiation into alcohol, cannabis and cigarette use has changed in Australia since the early 2000s.Data came from six waves of the Australian National Drug Strategy Household Survey, spanning 2001-2016. We used data from 18 to 21 year-olds (n = 6849) and examined trends in the age at first use for each of the three substances plus any changes in the order of initiation.The mean age of initiation increased steadily for all three substances (e.g. from 14.9 in 2001 to 16.4 in 2016 for alcohol), while the prevalence of any use declined. There were some changes in ordering of use. For example, in 2001, 62 % of respondents who used both cigarettes and cannabis had first used cigarettes at an earlier age than cannabis, compared with 41 % in 2016. Young people who used both alcohol and cannabis remained more likely to try alcohol before cannabis across the study period.Our results partly replicated US findings, with differences potentially reflecting the substantially different environment around these substances in the US compared to Australia. The age of initiation for alcohol, cigarette and cannabis use in Australia has increased sharply over the past 15 years.

The importance and complexity of addressing both substance use and mood disorders such as depression within traditional treatment settings is well established. However, little is known about this issue within the context of mHealth treatment. Research is needed to determine if depression interacts with mHealth delivered cannabis use disorder treatment similarly compared traditional treatments.We examined the moderating effect of depressive symptoms on cannabis use with 96 young adults (ages 18 to 25) enrolled in a text-delivered randomized clinical trial for cannabis use disorder. Participants were followed for three months.We used a repeated measures general linear model to test if depressive symptoms moderated the treatment's effect on cannabis use. Self-report of past 30-day use and urinalysis of THC metabolites were the outcome measures. Depressive symptoms were measured using the PHQ-2, with scores >3 serving as the clinical cut-point, indicating likely depression disorder.Participants with sub-threshold depression scores significantly reduced the number of days they used cannabis across all three months of the study. For participants with scores above the clinical cut-point, treatment had no effect on cannabis use. Similarly, participants with sub-threshold depression scores reduced the number of positive urinalysis results at three months. Effect sizes ranged from small to medium.Results support the importance of simultaneously addressing depressive symptoms and cannabis use when treating young adults using text-delivered counseling. As mHealth interventions continue to demonstrate efficacy in addressing substance use disorders, the integration of mood disorder treatments appears warranted.

Apart from being used as a medicine, cannabis or marijuana is the most widely abused recreational drug all over the world. The legalization and decriminalization of cannabis in Canada and various states of USA may be the underlying reason of the widespread popularity of it among young population. Various studies have reported about the relationship between cannabis use and different detrimental effects like cardiovascular, cerebrovascular, and neurological complications among different age groups. Specifically, the young population is getting adversely affected by this, harmful yet, readily accessible recreational drug. Although the mechanism behind cannabis mediated neurological and cerebrovascular complications has not been elucidated yet, the results of these studies have confirmed the association of these diseases with cannabis. Given the lack of comprehensive study relating these harmful complications with cannabis use, the aim of this narrative literature review article is to evaluate and summarize current studies on cannabis consumption and cerebrovascular/neurological diseases along with the leading toxicological mechanisms.

Road traffic crashes (RTCs) can cause serious and long-lasting consequences for drivers, both in terms of physical and mental health outcomes. Posttraumatic stress disorder (PTSD) is the most frequent mental disorder occurring after traumatic exposure. Ethiopian drivers experience RTCs more frequently than other sub-Saharan countries. Despite this prevailing phenomenon, limited attention has been given to PTSD among drivers.To determine the prevalence of PTSD and associated factors among drivers surviving RTCs in southwest Ethiopia.A cross-sectional quantitative study was conducted among 402 male drivers who had survived RTCs. The study was conducted in Jimma zone, southwest Ethiopia from March to June, 2019. All drivers who had survived RTCs in the last year were included in the study. The Trauma Screening Questionnaire was used to determine the prevalence of PTSD. Data were entered in EpiData 3.1 and exported to SPSS 24 for analysis.The response rate of the study was 398(99%). Fifty of 398 (12.6%, 95% CI 9.5%-16.1%) met PTSD criteria based on the questionnaire. A history of near-miss RTCs (AOR 3.49, 95% CI 1.89-6.43), depression (AOR 3.32, 95% CI 1.36-5.12), and severe-risk cannabis use (AOR 2.51, 95% CI 1.96-7.52) were significantly associated with PTSD.The prevalence of PTSD among drivers surviving RTCs was high compared to the general population. A record of near-miss RTCs, depression, and severe-risk cannabis use shown significant associations with PTSD. Strategies and guidelines must be developed to screen and treat PTSD among drivers surviving RTCs. Drivers with experience of near-miss RTCs, depression, and severe-risk cannabis use should be given priority when screening for PTSD.

Marijuana consumption is growing in the United States because of state legalization for recreational and medical use. However, many anesthesia practitioners are unaware of the potential adverse effects that may occur if marijuana is taken before the administration of an anesthetic. This review provides a history of marijuana use, the current laws and regulations, the pharmacology of marijuana, and best evidence-based practices related to anesthetic care of the marijuana user.

To compare cannabis enthusiasts' knowledge about cannabis risks and effectiveness in treating medical conditions with existing empirical evidence.A brief survey assessed cannabis use, information sources, and knowledge about risks and effectiveness.A cannabis advocacy event in April 2019 in a state with legal medical and recreational cannabis.Demographically diverse adults (N = 472) who frequently used cannabis; 85% used cannabis for health or medical purposes.Participants reported the sources of their cannabis information, health conditions they thought cannabis was effective in treating (n = 10), and health risks increased by cannabis (n = 6). Conditions and risks were based on ratings of evidence (ie, from substantial to insufficient) for therapeutic effects and risks identified in a review by The National Academies of Sciences, Engineering, and Medicine (NASEM, 2017).Chi-square tests examined the correspondence between participants' knowledge and NASEM conclusions.Most participants' (95% confidence interval [CI]: 74%-81%) knowledge of cannabis was from their own experiences; 18% (95% CI: 14%-21%) received information from primary care providers. On average, participants' beliefs matched NASEM conclusions for half of effectiveness (95% CI: 50%-53%) and risk items (95% CI: 55%-57%). Many (95% CI: 38%-42%) thought that cannabis use did not increase any risk. Contrary to NASEM conclusions, many thought cannabis was effective in treating cancer (76%), depressive symptoms (72%), and epilepsy (68%). Those who received cannabis information from their primary care providers had better knowledge of medical effectiveness. Medicinal cannabis use frequency inversely predicted knowledge of medical effectiveness and increased risks of adverse events.There were considerable discrepancies between cannabis users' knowledge and available evidence, highlighting the need for more research and education (by physicians, caregivers, and dispensaries) on effectiveness and health risks, especially for users with specific health issues such as pregnant women and people with depression.

CBD was shown to have anti-seizure activity based on in vitro and in vivo models. However, several reports of small series or case reports of the use of cannabis extracts in epilepsy yielded contradictory results and the efficacy of cannabis use in patients with epilepsy have also been inconclusive. In 2013, the first Phase 1 trial for a purified form of CBD (Epidiolex/Epidyolex; >99% CBD), developed by GW Pharma, showed some efficacy signals and subsequently, a comprehensive program on the efficacy and tolerability of this compound for the treatment of drug-resistant epilepsies was initiated. Results of these trials led to the FDA and EMA approval respectively in 2018 and 2019 for the treatment of seizures associated with two rare epilepsies: Lennox-Gastaut syndrome (LGS) or Dravet syndrome (DS) in patients two years of age and older. Thus, CBD became the first FDA-approved purified drug substance derived from cannabis and also the first FDA-approved drug for the treatment of seizures in DS. We detail the clinical studies using purified CBD (Epidiolex/Epidyolex), including the first open interventional exploratory study and Randomized Control Ttrials for DS and LGS.

The marijuana purchase task (MPT) is a behavioral economic measure of individualized cannabis value (i.e., demand). The MPT follows purchase tasks for other substances (e.g., alcohol, tobacco), though presents with unique caveats due to its mixed illicit status, non-uniform units of purchase and use, and substantial within substance variability in strain, potency, and quality. As the regulatory climate surrounding purchase and use of cannabis continues to evolve in the USA and globally, rigorous assessment of cannabis use and value are of the utmost importance. This study represents the first comprehensive review of investigations utilizing the MPT. Searches through PubMed and Web of Science databases by two independent coders identified 15 empirical articles referencing the use of an MPT and were published through the year 2019. Articles were coded for demographic and procedural characteristics, structural characteristics of the MPT itself, data analytic characteristics, and relationships with cannabis-related outcomes. Rigorous assessment of demand for cannabis is essential with respect to the broad public health issues surrounding cannabis legalization. We have synthesized the research presented herein and comment on vital considerations for subsequent MPT work, including recommendations for a unified approach to using the MPT in subsequent research.

Cannabis legalization at the US state level may have implications for cross-border purchases and diversion of legal products. The current study examined the association between out-of-state purchases and 1) cannabis regulations; and 2) the length of time a state has had recreational retail sales.Data come from US respondents who participated in Wave 1 of the International Cannabis Policy Study (ICPS), conducted in August-October 2018. Respondents were aged 16-65 years who had used cannabis in the past 12 months (n = 4320). Respondents were recruited using the Nielsen Consumer Insights Global Panel. Binary logistic regression models examined likelihood of any out-of-state cannabis purchases in the prior year, including differences by cannabis regulations, and time since recreational cannabis retail sales began.Overall, 15.0 % of US cannabis users had made any out-of-state cannabis purchases in the past 12 months. Respondents in states where recreational cannabis was legal were less likely to make any out-of-state purchases than respondents in states where only medical cannabis was legal (AOR = 0.45, 95 % CI: 0.34-0.60, p < 0.001) and where all cannabis was prohibited (AOR = 0.36, 95 % CI: 0.26-0.50, p < 0.001). Among respondents in 'legal' states, a longer history of legal sales was associated with a lower likelihood of out-of-state cannabis purchases (AOR = 0.82, 95 % CI: 0.72-0.93, p = 0.002).The findings demonstrate that consumers in states where recreational cannabis is legal were less likely to purchase cannabis out-of-state than consumers in states where recreational cannabis is not legal. Future research should examine which states people travel to purchase cannabis and why.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition that disproportionately affects women and is associated with significant physical and psychosocial impact. Recent studies have reported an increased prevalence of substance abuse among patients with HS, including increased alcohol, opioid, and cannabis use. Whether substance use disorder is more prevalent among patients with HS is controversial because these data come from small studies and a major confounder is that patients with HS are often prescribed opioids for HS-associated pain. This review summarizes the current literature on substance use in HS to investigate whether substance use disorder is more likely in this patient population. We also highlight possible cofounders and areas of unmet need in HS that are potential causes of abuse, such as adequate pain control and impaired quality of life, and suggest opportunities for provider intervention. Evidence suggests that there is an increased prevalence of substance use disorder in patients with HS, but the full extent is still difficult to determine. However, with early screening and appropriate referrals to specialists, dermatologic providers may properly intervene and prevent substance use disorder in patients with HS.

Given that risk perception has been found to be both a vulnerability and a protective factor with respect to consumption, the objectives of this study were to find out whether there exist specific patterns of risk perception associated with cannabis use and, if so, how they relate to cannabis consumption and to the sources of information on drugs accessed by young people. An ex post facto study was carried out with 1851 young Andalusians aged 18 to 29, using an adaptation of the Andalusian Government "Andalusian Population versus Drugs" survey. For the first objective, a cluster analysis was carried out in which three perceptual style groups were formed: "Strict", "Permissive-Awareness" and "Lax". Cannabis use in the "lax" group was found to be 14.31 times more frequent than in the "strict" group and 2.75 times more frequent than in the "permissive-awareness" group. A logistic regression analysis was also performed, which correctly predicted 80.4% of users and non-consumers. Correlation was found between perceptual styles and the sources of information used about drugs. This study identified three different risk perception styles that heavily correlated to cannabis consumption and to the type of sources young Andalusians use to obtain information about drugs, suggesting the need for a change in preventive policy.

The legal sale of cannabis-enriched foods and beverages for medical or recreational purposes is increasing in many states and countries, especially in North America and Europe. These food-based cannabis delivery systems vary considerably in their compositions and structures, ranging from low-viscosity watery beverages to solid fatty chocolates. The rate and extent of release of the bioactive components in cannabis within the human gastrointestinal tract (GIT) affect their health and psychoactive effects. Studies with other types of hydrophobic bioactives, such as nutraceuticals and vitamins, have shown that food composition and structure have a major impact on their bioaccessibility, transformation, and absorption within the GIT, thereby influencing their bioavailability and bioactivity. This review outlines how insights on the bioavailability of other lipophilic bioactives can be used to facilitate the design of more efficacious and consistent cannabis-enriched products intended for oral consumption. In particular, the importance of food-matrix composition (such as fat type and level) and structural organization (such as fat domain dimensions) are discussed. Expected final online publication date for the Annual Review of Food Science and Technology, Volume 11 is March 25, 2020. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

While there is a vast literature on rural and urban differences in substance use, little is known in terms of cannabis positive drug tests among fatally injured drivers. In the present study, we examined rural-urban differences in cannabis detected in fatally-injured drivers. Data were drawn from the 2015-2017 Fatality Analysis Reporting System. Multivariable logistic regression was performed to examine rural-urban differences in the percentage of cannabis detected in fatally-injured drivers. Analyses were stratified by rural-urban classification and sex. A positive cannabis test in fatally-injured drivers was more prevalent in urban locations. Compared to fatally-injured drivers in rural locations, urban drivers had higher odds of a positive test for cannabinoids (aOR: 1.21, 95% CI 1.14-1.28). Non-Hispanic Black drivers had higher odds of testing positive for cannabinoids (aOR: 1.43, 95% CI 1.31-1.55). Those aged at least 25 years had lower odds of a positive test for cannabinoids. Drivers involved in a weekend nighttime crash (aOR: 1.14, 95% CI 1.03-1.26) and weekday nighttime (aOR: 1.15, 95% CI 1.05-1.26) had higher odds of testing positive for cannabinoids compared to drivers involved in a weekend daytime crash. Results showed significant rural-urban differences in the prevalence of cannabis detected in fatally-injured drivers.

There has been a recent increase in recognition of lung disease related to the use of electronic cigarettes (called "vaping"). These patients present with acute respiratory illness following exposure to vaporized cannabis or nicotine products and sometimes require hospitalization and intensive care. We describe the imaging findings of this disease entity in the pediatric population.To describe the radiologic findings of lung injury associated with electronic cigarette use (vaping) in the adolescent pediatric population.We identified all adolescents with acute respiratory illness and a history of electronic cigarette use who presented at our institution within a 3-month period (June 2019 through August 2019). We excluded adolescents with potential intercurrent pulmonary disease. We reviewed the charts for symptomatology and laboratory and pathology data. In addition, we reviewed the chest radiographs and chest CTs of these adolescents.The review group consisted of 12 teenage pediatric patients (10 boys and 2 girls; mean age 16.9 years, range 16.0-17.7 years) with acute respiratory illness found to have a temporal association with electronic cigarette use for cannabis products, nicotine, or both. Other etiologies for illness in these adolescents had been excluded by clinical and laboratory evaluation. All of the adolescents were admitted to the hospital for treatment. The clinical presentations included dyspnea, abdominal pain and constitutional symptoms. Pulmonary function testing that was performed in all patients during admission or follow-up demonstrated reduced diffusion capacity in 4/12 (33%), an obstructive ventilatory pattern in 4/12 (33%), a restrictive pattern in 1/12 (8%), and a mixed obstructive and restrictive pattern in 2/12 (17%) adolescents. Bronchoalveolar lavage studies, performed in 9 of the 12 adolescents, revealed inflammatory cells and lipid-laden macrophages. All of the patients underwent CT of the chest; the findings were notable for centrilobular ground-glass nodules (11/12; 92%) and confluent ground-glass opacities (12/12; 100%), with frequent subpleural sparing (9/12; 75%). Additionally, 6/12 (50%) adolescents demonstrated small pleural effusions; 6/12 (50%) had mild bronchial wall thickening; 9/12 (75%) had enlarged hilar or mediastinal lymph nodes; and 2/12 (17%) had a small pericardial effusion.As seen in our teenage population, e-cigarette, or vaping, product use-associated lung injury (EVALI) is characterized by centrilobular ground-glass nodules and ground-glass opacities with subpleural sparing. The imaging findings are most consistent with acute lung injury resulting from toxic inhalation. Because adolescent pediatric patients might not be forthcoming with their history of electronic cigarette use, it is important for the pediatric radiologist to be aware of the imaging patterns of this disease.

The legalization of cannabis for both recreational and medical use in the USA has resulted in a dramatic increase in the number of emergency department visits and hospital admissions for acute cannabinoid overdose (also referred to as cannabis intoxication and cannabis poisoning). Both "edibles" (often sold as brownies, cookies, and candies) containing large amounts of Δ9-tetrahydrocannabinol and synthetic cannabinoids (many possessing higher potencies and efficacies than Δ9-tetrahydrocannabinol) are responsible for a disproportionate number of emergency department visits relative to smoked cannabis. Symptoms of acute cannabinoid overdose range from extreme lethargy, ataxia, and generalized psychomotor impairment to feelings of panic and anxiety, agitation, hallucinations, and psychosis. Treatment of acute cannabinoid overdose is currently supportive and symptom driven. Converging lines of evidence indicating many of the symptoms which can precipitate an emergency department visit are mediated through activation of cannabinoid1 receptors. Here, we review the evidence that cannabinoid1 receptor antagonists, originally developed for indications ranging from obesity to smoking cessation and schizophrenia, provide a molecular approach to treating acute cannabinoid overdose.

Neuropathic pain associated with nucleoside reverse transcriptase inhibitors (NRTIs), therapeutic agents for human immunodeficiency virus (HIV), responds poorly to available drugs. Smoked cannabis was reported to relieve HIV-associated neuropathic pain in clinical trials. Some constituents of cannabis (Cannabis sativa) activate cannabinoid type 1 (CB1) and cannabinoid type 2 (CB2) receptors. However, activation of the CB1 receptor is associated with side effects such as psychosis and physical dependence. Therefore, we investigated the effect of β-caryophyllene (BCP), a CB2-selective phytocannabinoid, in a model of NRTI-induced neuropathic pain. Female BALB/c mice treated with 2'-3'-dideoxycytidine (ddC, zalcitabine), a NRTI, for 5 days developed mechanical allodynia, which was prevented by cotreatment with BCP, minocycline or pentoxifylline. A CB2 receptor antagonist (AM 630), but not a CB1 receptor antagonist (AM 251), antagonized BCP attenuation of established ddC-induced mechanical allodynia. β-Caryophyllene prevented the ddC-induced increase in cytokine (interleukin 1 beta, tumor necrosis factor alpha and interferon gamma) transcripts in the paw skin and brain, as well as the phosphorylation level of Erk1/2 in the brain. In conclusion, BCP prevents NRTI-induced mechanical allodynia, possibly via reducing the inflammatory response, and attenuates mechanical allodynia through CB2 receptor activation. Therefore, BCP could be useful for prevention and treatment of antiretroviral-induced neuropathic pain.

Monitoring pharmacological active compounds in pharmaceutical preparations of medical cannabis and in conventional and non-conventional biological matrices of treated individuals use requires both a wide linear range and sensitive detection. We have developed and validated a fast and sensitive method using ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS) for analysis of Δ-9-tetrahydrocannabinol (THC), cannabidiol (CBD), their acidic precursors Δ-9-tetrahydrocannabinolic acid A (THCA-A) and cannabidiolic acid (CBDA) and some major metabolites of THC such as 11-nor-9-carboxy-THC (THC-COOH), 11-hydroxy-THC (11-OH-THC), Δ-9-THC-Glucuronide (THC-GLUC) and THC-COOH-Glucuronide (THC-COOH-GLUC) in conventional (whole blood and urine) and non-conventional (oral fluid and sweat) of individual treated with medical cannabis preparation. Specifically, THC, THCA-A, CBD and CBD-A were determined in cannabis decoction and oil prepared to treat individuals. The method used positive electrospray ionization (ESI) mode to reach the sensitivity needed to detect minimal amounts of analytes under investigations exposure with limits of quantification ranging from 0.2 to 0.5 ng per milliliter (ng/mL) or ng per patch in case of collected sweat. The validation results indicated this method was accurate (average inter/intra-day error, <10%), precise (inter/intra-day imprecision, <10%), and fast (10 min run time). In addition, time-consuming sample preparation was avoided applying dilute and shoot procedure, meeting the needs for potential large-scale population studies. The analysis of real samples demonstrated a pharmacokinetics of cannabinoids, their precursors and their metabolites dependent from quantity of carboxylated and decarboxylated compounds in pharmaceutical preparations.

Polyphenols are a broad class of plant secondary metabolites which carry out several biological functions for plant growth and protection and are of great interest as nutraceuticals for their antioxidant properties. However, due to their structural variability and complexity, the mass-spectrometric analysis of polyphenol content in plant matrices is still an issue. In this work, a novel approach for the identification of several classes of polyphenol derivatives based on ultra-high performance liquid chromatography coupled to high-resolution mass spectrometry was developed. First, mass-spectrometric parameters were optimized in order to obtain a large set of diagnostic product ions for their high-confidence identification. The software Compound Discoverer 3.0 was then implemented with a comprehensive database of 45,567 polyphenol derivatives and with mass-spectrometric data for their building blocks, resulting in a specific tool for the semi-automatic identification of flavonoids, anthocyanins, ellagitannins, proanthocyanidins and phenolic acids. The method was then applied to the identification of polyphenols in industrial hemp (Cannabis sativa), a matrix whose use is recently spreading for pharmaceutical and nutraceutical purposes, resulting in the identification of 147 compounds belonging to the classes of flavonoids, proanthocyanidins and phenolic acids. The proposed method is applicable to the polyphenol profiling of any plant matrix and it is not dependent on data in the literature for their identification, allowing the discovery of compounds which have been never identified before.

Precipitants of alcohol use transitions can differ from generalized risk factors. We extend prior research by predicting transitions in alcohol use disorder (AUD) during adolescence and emerging adulthood.From 12/2009-9/2011, research assistants recruited 599 drug-using youth age 14-24 from Level-1 Emergency Department in Flint, Michigan. Youth were assessed at baseline and four biannual follow-ups, including a MINI Neuropsychiatric interview to diagnose AUD (abuse/dependence). We modeled AUD transitions using continuous time Markov Chains with transition probabilities modulated by validated measures of demographics, anxiety/depression symptoms, cannabis use, peer drinking, parental drinking, and violence exposure. Separate models were fit for underage (<21) and those of legal drinking age.We observed 2,024 pairs of consecutive AUD states, including 264 transitions (119 No-AUD→AUD; 145 AUD→No-AUD); 194 (32.4%) individuals were diagnosed with AUD at ≥1 assessment. Among age 14-20, peer drinking increased AUD onset (No-AUD→AUD transition) rates (Hazard ratio-HR = 1.70; 95%CI: [1.13,2.54]), parental drinking lowered AUD remission (AUD→No-AUD transition) rates (HR = 0.53; 95%CI: [0.29,0.97]), and cannabis use severity both hastened AUD onset (HR = 1.18; 95%CI: [1.06,1.32]) and slowed AUD remission (HR = 0.85; 95%CI: [0.76,0.95]). Among age 21-24, anxiety/depression symptoms both increased AUD onset rates (HR = 1.35; 95%CI: [1.13,1.60]) and decreased AUD remission rates (HR = 0.74; 95%CI: [0.63,0.88]). Friend drinking hastened AUD onset (HR = 1.18, 95%CI: [1.05,1.33]), and slowed AUD remission (HR = 0.84; 95%CI: [0.75,0.95]). Community violence exposure slowed AUD remission (HR = 0.69, 95%CI: [0.48,0.99]). In both age groups, males had >2x the AUD onset rate of females, but there were no sex differences in AUD remission rates. Limitations, most notably that this study occurred at a single site, are discussed.Social influences broadly predicted AUD transitions in both age groups. Transitions among younger youth were predicted by cannabis use, while those among older youth were predicted more by internalizing symptoms and stress exposure (e.g., community violence). Our results suggest age-specific AUD etiology, and contrasts between prevention and treatment strategies.

Behavioral addictions (BAs) and substance use disorders (SUDs) tend to co-occur; both are associated with mental health problems (MHPs). This study aimed to estimate the proportion of variance in the severity of MHPs explained by BAs and SUDs, individually and shared between addictions.A sample of 5,516 young Swiss men (mean = 25.47 years old; SD = 1.26) completed a self-reporting questionnaire assessing alcohol, cannabis, and tobacco use disorders, illicit drug use other than cannabis, six BAs (Internet, gaming, smartphone, Internet sex, gambling, and work) and four MHPs (major depression, attention-deficit hyperactivity disorder, social anxiety disorder, and borderline personality disorder). Commonality analysis was used to decompose the variance in the severity of MHPs explained (R2) by BAs and SUDs into independent commonality coefficients. These were calculated for unique BA and SUD contributions and for all types of shared contributions.BAs and SUDs explained between a fifth and a quarter of the variance in severity of MHPs, but individual addictions explained only about half of this explained variance uniquely; the other half was shared between addictions. A greater proportion of variance was explained uniquely or shared within BAs compared to SUDs, especially for social anxiety disorder.The interactions of a broad range of addictions should be considered when investigating their associations with MHPs. BAs explain a larger part of the variance in MHPs than do SUDs and therefore play an important role in their interaction with MHPs.

The butyl homologues of Δ9-tetrahydrocannabinol, Δ9-tetrahydrocannabutol (Δ9-THCB), and cannabidiol, cannabidibutol (CBDB), were isolated from a medicinal Cannabis sativa variety (FM2) inflorescence. Appropriate spectroscopic and spectrometric characterization, including NMR, UV, IR, ECD, and HRMS, was carried out on both cannabinoids. The chemical structures and absolute configurations of the isolated cannabinoids were confirmed by comparison with the spectroscopic data of the respective compounds obtained by stereoselective synthesis. The butyl homologue of Δ9-THC, Δ9-THCB, showed an affinity for the human CB1 (Ki = 15 nM) and CB2 receptors (Ki = 51 nM) comparable to that of (-)-trans-Δ9-THC. Docking studies suggested the key bonds responsible for THC-like binding affinity for the CB1 receptor. The formalin test in vivo was performed on Δ9-THCB in order to reveal possible analgesic and anti-inflammatory properties. The tetrad test in mice showed a partial agonistic activity of Δ9-THCB toward the CB1 receptor.

Florida became the first state in the U.S. South to legalize the use of medical marijuana to treat a variety of health conditions including chronic pain, epilepsy, and spasticity symptoms from multiple sclerosis. While there are over 200,000 medical marijuana patients in Florida, there remain financial, psychological, and insurance coverage barriers which reduce access for many patients.This scoping review, with a focus on state health policy, first describes some clinical studies examining the therapeutic benefits of medical marijuana. Next, there is a discussion of the Florida regulatory environment and major legislation. Also, the review describes how the current Florida policy landscape presents challenges for physicians and patients.A scoping review of the literature was conducted in PubMed and Google Scholar using the search terms, "medical marijuana" and "medical cannabis" to identify research articles, newspaper reports, and government documents. The purpose of the review was to identify research investigating the therapeutic efficacy of medical marijuana and state policies affecting physician practice.The review concluded there was general scientific consensus of therapeutic benefits for patients, especially for chronic pain, from the use of medical marijuana. The review also identified several barriers for physicians and patients around cost, stigma, and lack of insurance coverage which constrains use and access.The review discusses several directions for future medical marijuana policy and research with the aim to improve therapeutic benefits for Florida patients.

Trials demonstrate the effectiveness of web-based interventions for cannabis-related disorders. For further development of these interventions, it is of vital interest to identify user characteristics which predict treatment response.Data from a randomized factorial trial on a web-based intervention for cannabis-users (n = 534) was reanalyzed. As potential predictors for later treatment response, 31 variables from the following categories were tested: socio-demographics, substance use and cognitive processing. The association of predictors and treatment outcome was analyzed using unbiased recursive partitioning and represented as classification tree. Predictive performance of the tree was assessed by comparing its cross-validated results to models derived with all-subsets logistic regression and random forest.Goal commitment (p < .001), the extent of self-reflection (p < .001), the preferred effect of cannabis (p = .005) and initial cannabis use (p = .015) significantly differentiate between successful and non-successful participants in all three analysis methods. The predictive accuracy of all three models is comparable and modest.Participants who commit to quit using cannabis, who at least have moderate levels of self-reflection and who prefer mild intoxicating effects were most likely to respond to treatment. To predict treatment response on an individual level, the classification tree should only be used as one of several sources of information.Trial registration: http://www.isrctn.com/ISRCTN99818059.

The raised demand of cannabis as a medicinal plant in recent years led to an increased interest in understanding the biosynthetic routes of cannabis metabolites. Since there is no established protocol to generate stable gene knockouts in cannabis, the use of a virus-induced gene silencing (VIGS) method, resulting in a gene knockdown, to study gene functions is desirable.For this, a computational approach was employed to analyze the Cannabis sativa L. transcriptomic and genomic resources. Reporter genes expected to give rise to easily scorable phenotypes upon silencing, i.e. the phytoene desaturase (PDS) and magnesium chelatase subunit I (ChlI), were identified in C. sativa. Subsequently, the targets of specific small interfering RNAs (siRNAs) and silencing fragments were predicted and tested in a post-transcriptional gene silencing (PTGS) approach. Here we show for the first time a gene knockdown in C. sativa using the Cotton leaf crumple virus (CLCrV) in a silencing vector system. Plants transiently transformed with the Agrobacterium tumefaciens strain AGL1, carrying the VIGS-vectors, showed the desired phenotypes, spotted bleaching of the leaves. The successful knockdown of the genes was additionally validated by quantitative PCR resulting in reduced expression of transcripts from 70 to 73% for ChlI and PDS, respectively. This is accompanied with the reduction of the chlorophyll a and carotenoid content, respectively. In summary, the data clearly demonstrate the potential for functional gene studies in cannabis using the CLCrV-based vector system.The applied VIGS-method can be used for reverse genetic studies in C. sativa to identify unknown gene functions. This will gain deeper inside into unknown biosynthetic routes and will help to close the gap between available genomic data and biochemical information of this important medicinal plant.

The presence of mental distress among students affects their cognitive, emotional, physical, and interpersonal functioning. Besides, it predisposes to substance use problems and finally affects academic performance negatively. Therefore, this study was designed to estimate the magnitude and identify associated factors for the mental distress of students at Wollo University, Dessie, Ethiopia.This institution-based cross-sectional survey assessed mental distress among 585 undergraduate students at Wollo University from April 10 to May 10/2019 using a multi-stage stratified sampling technique. Kessler-10 item scale was used to collect data about mental distress. Variables with p-value < 0.25 in bivariate logistic regression were pooled into a multi-variable logistic regression model and p-value < 0.05 in the multi-variable model was considered significant statistically. The strength of the relationship was interpreted using the odds ratio with 95% CI. The model adequacy in multi-variable regression was approved with Hosmer and Lemeshow goodness of fit test.Among 585 questionnaires distributed, 548 clear and completed questionnaires were included in the analysis with a response rate of 93.7%. The mental distress prevalence in the current study was 106 (19.3%). From this 65 (11.9%), 28 (5.1%), and 13 (2.4%) were found to be mild, moderate and severe mental distress respectively. Never attending a place of worship (AOR = 4.2, 95% CI 1.73, 10.39), family history of mental illness (AOR = 2.1, 95% CI 1.12, 3.95), current cigarette smoking (AOR = 3.2, 95% CI 1.69, 6.20), current alcohol use (AOR = 2.5, 95% CI 1.49, 4.25), and current cannabis use (AOR = 3.4, 95% CI 1.18, 9.57) were the associated factors for mental distress.One in five students was affected by mental distress. Never attending a place of worship, family history of mental illness, current cigarette smoking, current alcohol use, and current cannabis use were the factors associated with it. Therefore, all stakeholders should be involved in overcoming this public health problem. Besides, clubs should be established in the university and have to play an active role in bringing behavioral change to substance use.

(-)-Trans-Δ9-tetrahydrocannabinol (Δ9-THC) is the main compound responsible for the intoxicant activity of Cannabis sativa L. The length of the side alkyl chain influences the biological activity of this cannabinoid. In particular, synthetic analogues of Δ9-THC with a longer side chain have shown cannabimimetic properties far higher than Δ9-THC itself. In the attempt to define the phytocannabinoids profile that characterizes a medicinal cannabis variety, a new phytocannabinoid with the same structure of Δ9-THC but with a seven-term alkyl side chain was identified. The natural compound was isolated and fully characterized and its stereochemical configuration was assigned by match with the same compound obtained by a stereoselective synthesis. This new phytocannabinoid has been called (-)-trans-Δ9-tetrahydrocannabiphorol (Δ9-THCP). Along with Δ9-THCP, the corresponding cannabidiol (CBD) homolog with seven-term side alkyl chain (CBDP) was also isolated and unambiguously identified by match with its synthetic counterpart. The binding activity of Δ9-THCP against human CB1 receptor in vitro (Ki = 1.2 nM) resulted similar to that of CP55940 (Ki = 0.9 nM), a potent full CB1 agonist. In the cannabinoid tetrad pharmacological test, Δ9-THCP induced hypomotility, analgesia, catalepsy and decreased rectal temperature indicating a THC-like cannabimimetic activity. The presence of this new phytocannabinoid could account for the pharmacological properties of some cannabis varieties difficult to explain by the presence of the sole Δ9-THC.

Self-regulation deficits expressed through a decreased ability to value future rewards (delay discounting (DD)) and impaired emotion regulation (negative urgency (NU), cannabis coping motives (CCM), and anxiety sensitivity (AS)) relate to more frequent or problematic cannabis use. However, there is a need to better understand how self-regulation and emotion regulation constructs reflect competition between deliberative and reactive systems that drive individual differences in cannabis use patterns. Further, few studies assess frequency of cannabis use within and across days of use, which may obscure differentiation of individual differences.In a large national sample of 2545 cannabis users, Latent Class Analysis was used to derive participant sub-classes based on two frequency indices, self-reported cannabis use days and times cannabis was used per day. Three classes emerged: Low (1-9 days/month, 1 time/day; 23 %), moderate (10-29 days/month, 2-3 times/day; 41 %), and high (30 days/month, ≥4 times/day; 36 %). Relationships among frequency classes and emotional regulation and impulsivity were assessed with a multinomial logistic regression.Higher frequency use was associated with greater DD (χ2 = 6.0, p = .05), greater CCM (χ2 = 73.3, p < .001), and lower cognitive AS (χ2 = 12.1, p = .002), when controlling for demographics, tobacco use, and number of cannabis administration methods. Frequency class and NU were not significantly associated.Identifying meaningful patterns of cannabis use may improve our understanding of individual differences that increase risk of frequent or problematic cannabis use. Excessive delay discounting and using cannabis to cope with negative affect may be relevant targets for treatments designed to reduce cannabis use.

Studies show that patients with cancer use cannabis to manage symptoms and side effects. Medical cannabis is regulated by Health Canada; authorization patterns among cancer patients have not been well described.The aim of the study is to describe medical cannabis authorization in Alberta, Canada.The Alberta Cancer Registry was used to identify all patients aged 18 years and older diagnosed with invasive cancer from April 1, 2014 to December 31, 2016. These cases were linked to records from the College of Physicians and Surgeons of Alberta. Univariate and multivariate logistic regression models were constructed to determine factors associated with medical cannabis authorization.We identified 41,889 patients with cancer between April 1, 2014 and December 31, 2016. Of these patients, 1070 (2.6%) had a medical cannabis authorization. Fifty-one percent (541 of 1070) were authorized to use medical cannabis within one year of diagnosis, 52% (248 of 549) within one year of the start of systemic therapy, and 41% (128 of 312) within one year of the start of radiation therapy. Patients aged 18-29 (odds ratio [OR] 12.4; 95% CI 7.8-19.8), patients living in the Calgary zone (OR 1.8; 95% CI 1.6-2.1), those with advanced disease (Stage III/IV: OR 1.2; 95% CI 1.0-1.4), and those receiving systemic therapy (OR 2.0; 95% CI 1.7-2.4) were more likely to have an authorization for medical cannabis (P < 0.001).A small proportion of patients with cancer were authorized to use medical cannabis between 2014 and 2016 in Alberta. Authorization was associated with a cancer diagnosis and receiving treatment. Younger patients, those with advanced stage disease, and those undergoing systemic treatment were predictors of medical cannabis authorization.

Although there is a consensus that cannabis intoxication will have deleterious effects on a wide spectrum of cognitive skills, there is no consensus regarding the duration of time from last use necessary to ameliorate these effects.A systematic review and series of meta-analyses were undertaken to assess anticipated gains in verbal learning with longer periods of cannabis abstinence. Studies assessing verbal learning performance in abstinent regular cannabis users and nonusing control participants; studies reporting length of cannabis abstinence at the time of neuropsychological assessment; and studies implementing one of three highly comparable measures of verbal learning and memory were included in the analyses. The included tasks have demonstrated some of the most robust declines associated with cannabis use and are prevalent in the clinical practice of neuropsychology. We assessed associations between cannabis abstinence and verbal learning scores via mixed effects subgroup analyses.Twenty-three studies (k = 28; N = 1,711) met all inclusion criteria. Cannabis users abstinent for 7 days or fewer performed worse than controls on verbal learning tasks, whereas cannabis users abstinent for longer periods showed no average significant difference in verbal learning performance compared with controls.Based on available evidence, some amelioration of verbal learning limitations presumed to result from cannabis appear to resolve between 7 and 28 days of sustained abstinence. However, in the reviewed studies, years of regular use were inversely related to longer periods of abstinence and verbal learning performance, undermining a confident inference that abstinence alone has direct benefits to verbal learning and memory. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Objective To evaluate the demographic characteristics, hospitalization outcomes [severity, length of stay (LOS), and total expense], and comorbidities in pregnant patients with antepartum drug dependence (ADD). Methods We used the national inpatient sample (NIS) and included 19,170,561 female patients (age: 12-40 years) hospitalized for pregnancy- or birth-related complications and grouped by co-diagnosis of ADD. We used descriptive statistics and Pearson's chi-square test for categorical data and independent sample T-test for the continuous data to measure the differences in demographic and hospital outcomes. A logistic regression model was used to evaluate the odds ratio (OR) for medical and psychiatric comorbidities. Results The hospitalizations with ADD declined initially, from 2010 to 2011, followed by an increase of 50% from 2011 to 2014. White pregnant females (77.5%), and those from low-income families (<25th percentile, 37.1 %) had comorbid ADD. Among medical comorbidities, iron-deficiency anemia was the most prevalent condition in pregnant inpatients (12.0% in ADD vs. 9.2% in non-ADD) followed by obesity and hypertension. Depression (12.9%) was the most prevalent psychiatric comorbidity in ADD inpatients followed by comorbid psychosis (three-fold higher odds). Among patients with substance use disorder (SUD), opioid abuse was the most prevalent one (67.3%) followed by cannabis (11.2%), cocaine (5.7%), amphetamine (4.0%), and alcohol (2.4%). Half of the pregnant inpatients with ADD had moderate severity of illness due to pregnancy or birth-related complications with four-fold higher odds [95% confidence interval (CI): 3.67-8.88]. They also had a higher LOS with a mean difference of 0.88 days (95% CI: 0.904-0.865) and had incurred higher total charges, by USD 3,797 (95% CI: 3,927-3,666), per inpatient admission for pregnancy- or birth-related complications compared to non-ADD inpatients Conclusion ADD is associated with the worsening of severity of illness in pregnancy- or birth-related complications and requires acute inpatient care that leads to increased healthcare-related economic burden. The integration of SUD services with primary or maternal care is required to improve outcomes in at-risk women in the reproductive age group.

Cannabis sativa L. has been utilized for a long time as a traditional herbal medicine in Korea. Dry fruits, achenes, each containing a single seed of Cannabis, are currently prescribed as Ma In (Cannabis Semen), a laxative. As each achene is enclosed by a bract, in which tetrahydrocannabinol (THC), the main psychological active compound in Cannabis is synthesized; achene is easily contaminated by THC from bract remnants. Therefore, it is safer to harvest achenes from Cannabis with a low THC content. Seeds of hemp, a low THC Cannabis, were recently classified as possible sources of new pharmacologically active compounds. Thus, a proper method to select appropriate Cannabis plants with low THC among cultivars in South Korea for medicinal purpose is necessary. As a result of cross-selection, Cannabis L. cultivar "Cheungsam" (CH) with the lowest THC content among cultivars cultivated in South Korea has been developed. In this study, we developed two DNA markers to reliably discriminate CH from other local cultivars with higher THC contents. We developed primer sets CHF3/CHR2 to amplify the 642 bp DNA marker of CH based on differences in the nucleotide sequences of the THCA synthase gene, which encodes a key enzyme in THC synthesis. We then developed a CHF1/CHR3 primer set to amplify the 401 bp DNA marker of CH based on the differences in both the content of very long chain fatty acids (VLCFs) and the sequence of the putative 3-ketoacyl-CoA synthase (KCS) gene encoding enzymes synthesizing VLCFs among local cultivars.

Introduction. Before cigarettes became popular, lung cancer was an extremely rare disease, but currently it is the most common cause worldwide of cancer death in both genders. Therefore, it constitutes a huge epidemiological, diagnostic and socio-economic challenge around the world. In Poland, lung cancer is the second most common carcinoma in both men and women, and it is also the most prevailing cause of carcinous death. Undoubtedly, although smoking classical cigarettes is the strongest risk factor of developing the cancer, unfortunately it is not the only one. Objective. The aim of this study was to present smoking-related factors, e.g. cigars, pipes, e-cigarettes or marijuana smoking, etiologically related to lung cancer incidence.

Cannabidiol (CBD) is one of the main pharmacologically active phytocannabinoids of Cannabis sativa L. CBD is non-psychoactive but exerts a number of beneficial pharmacological effects, including anti-inflammatory and antioxidant properties. The chemistry and pharmacology of CBD, as well as various molecular targets, including cannabinoid receptors and other components of the endocannabinoid system with which it interacts, have been extensively studied. In addition, preclinical and clinical studies have contributed to our understanding of the therapeutic potential of CBD for many diseases, including diseases associated with oxidative stress. Here, we review the main biological effects of CBD, and its synthetic derivatives, focusing on the cellular, antioxidant, and anti-inflammatory properties of CBD.

Carbonated soft drink (CSD) intake has been associated with various risk behaviors in adolescents in high-income countries, but there is lack of evidence of this association in cross-nationally representative samples of school adolescents in low- and middle-income countries. This study aimed to assess the association between CSD intake, health risk behavior, and poor mental health behavior among school-going adolescents in six Southeast Asian countries. Cross-sectional national "Global School-Based Student Health Survey (GSHS)" data from 36173 school-going adolescents from Bangladesh, Indonesia, Laos, Philippines, Thailand, and Timor-Leste were analyzed. Results indicate that across all six Southeast Asian countries, in the past 30 days 23.9% of study participants had consumed no CSD, 38.8% had consumed CSD

Cannabis or cannabinoids produce characteristic tetrad effects-analgesia, hypothermia, catalepsy and suppressed locomotion, which are believed to be mediated by the activation of cannabinoid CB1 receptors. Given recent findings of CB2 and GPR55 receptors in the brain, we examined whether these receptors are also involved in cannabinoid action.We compared Δ9 -tetrahydrocannabinol (Δ9 -THC)-, WIN55212-2-, or XLR11-induced tetrad effects between wild-type (WT) and each genotype of CB1 -, CB2 - or GPR55-knockout (KO) mice and then observed the effects of antagonists of these receptors on these tetrad effects in WT mice.Systemic administration of Δ9 -THC, WIN55212-2 or XLR11 produced dose-dependent tetrad effects in WT mice. Genetic deletion or pharmacological blockade of CB1 receptors abolished the tetrad effects produced by all three cannabinoids. Unexpectedly, genetic deletion of CB2 receptor abolished analgesia and catalepsy produced by Δ9 -THC or WIN55212-2, but not by XLR11. Microinjections of Δ9 -THC into the lateral ventricles also produced tetrad effects in WT, but not in CB1 -KO mice. CB2 -KO mice displayed a reduction in intraventricular Δ9 -THC-induced analgesia and catalepsy. In contrast to CB1 and CB2 receptors, genetic deletion of GPR55 receptors caused enhanced responses to Δ9 -THC or WIN55212-2. Antagonisim of CB1 , CB2 or GPR55 receptors produced alterations similar to those observed in each genotype mouse line.These findings suggest that in addition to CB1 , both CB2 and GPR55 receptors are also involved in some pharmacological effects produced by cannabinoids. CB1 /CB2 , in contrast to GPR55, receptors appears to play opposite roles in cannabinoid action.

Cannabis use is increasing worldwide despite the various health effects of this substance.We report 2 cases of acute hippocampal encephalopathy in heavy cannabis users (>10 joints/d).In both male patients, acute encephalitis was suspected. Brain magnetic resonance imaging (MRI) diffusion-weighted sequences showed bilateral high signal abnormalities in hippocampal regions. Patients had renal dysfunction, rhabdomyolysis, and inflammatory syndrome. Investigations showed no evidence of infectious or autoimmune encephalitides. Repeated electroencephalograms revealed no epileptic activity. Clinical, biological, and magnetic resonance imaging acute abnormalities improved within weeks. New exposure to cannabis yielded a new episode of encephalopathy. In both patients, severe long-lasting episodic memory impairment associated with hippocampal atrophy were observed several months later.Health professionals should be aware of this cannabis-related syndrome given its severe and long-lasting effects.

Integration of psychiatric care at the Primary Health Care (PHC) could be an important strategy towards addressing the shortages of in-patient mental health care services in South Africa. This study describes the profiles of admitted psychiatric patients at the East London Mental Health Unit (ELMHU) of the Eastern Cape from January 2016 to December 2016.In this retrospective cross-sectional study, an audit of medical records of all psychiatric in-patients managed at the ELMHU during the study period was undertaken. Simple descriptive and inferential statistics were used to describe the profiles and examine the associations with the common psychiatric conditions.Of the participants with complete data (n = 186), the majority were males (n = 108); single (72.6%) and had secondary education (45.7%). The majority of in-patients were psychotic (38%), violent (31%), manic (16%) or suicidal (9.2%) at the time of admission. Patients who were 35 years and above, resided in urban areas, and presented with suicidal and depressive symptoms were more likely to be admitted voluntarily. Schizophrenia (31.6%), cannabis-related psychiatric disorders (31.6%), bipolar Type-1 disorder (21.9%) and alcohol related disorders (15.5%) were the main reasons for admission. There was a significant association between demographic characteristics and the common psychiatric disorders of the patients.Schizophrenia, bipolar 1 disorder, cannabis-related disorders and alcohol-related disorders are the predominant disorders leading to in- patient mental health care services being utilized in the study setting. Findings might inform training of health care workers at the PHCs with a view to integrating mental health care services in the Eastern Cape.

Background: Cannabis advertisement content in print media has not yet been studied, despite youth high exposure to them. This study analyzes cannabis ads content in two publications in Western Washington State, USA. Methods: Content analysis of 305 cannabis advertisements published in 2017 in two free print publications was performed with support of NVivo software. A deductive approach was utilized, leveraging alcohol advertisement studies' coding frames and adding cannabis-specific codes in an iterative process. Coding was performed using a two-step analytical procedure. Results: Ads depicted the use of cannabis as part of everyday life and coopted mainstream events such as holidays to promote sales. Ads of cannabis products emphasized lifestyles that conveyed enjoyment of time in nature; such as scenes of people sitting by waterfalls, contemplating natural landscapes, paddle boarding, and canoeing. A sizeable proportion of the cannabis ads shared with alcohol ads an emphasis on the personal and social rewards of using these products, rather than product features, such as quality and taste. Conclusions: In WA State, cannabis use ads content tend to focus on solitude and outdoor recreation rather than parties and team sports, a common theme in alcohol ads. While the themes differ from alcohol, marijuana marketing mimics strategies used by alcohol industries, such as promoting the identification of their products with lifestyles and values considered appealing to attract new consumers. Many ads presented content known to appeal to youth, with content designed to elicit responses based on emotions rather than cognition.

Although several studies have examined individual-level correlates of cannabis use in later life, there is scant evidence identifying heterogeneity among older users. Using data from Colorado, this study examines variability in lifespan patterns of cannabis use among individuals aged 60 years and older. Sample respondents reported cannabis use in the past year and frequency of use in four periods of adulthood. Analyses used a multi-way contingency table to identify mutually exclusive subgroups of cannabis users based on lifetime reports of use and linear probability models to identify predictors of group identity. Three subgroups of older cannabis users were identified: new users, stop-out or intermittent users, and consistent users. The three groups varied on current use frequency and method of ingestion, as well as social and health characteristics. Screening for past history of cannabis use may help health care providers identify older adults who need health information and monitoring related to cannabis use.

The shortage of new cannabis varieties with low THC and high CBD content and irregular planting techniques have become the bottleneck for he development of non-psychoactive medicinal cannabis industry. Based on the cannabis germplasm resources,this paper proposes strategies for breeding high CBD content,seed-type and high-efficiency,dwarf non-psychoactive medicinal cannabis varieties through molecular marker development,assisted breeding,genetic engineering breeding and traditional breeding. According to the suitable ecological factors of non-psychoactive medicinal cannabis,the CBD content and grain yield of non-psychoactive medicinal cannabis can be improved by regulating the nutritional structure and illumination properties of non-psychoactive medicinal cannabis,scientific harvesting and storage. At the same time,in order to further accelerate the application of non-psychoactive medicinal cannabis,we can accelerate the selection of new varieties of non-psychoactive medicinal cannabis by mining genetic information of cannabis,and strengthen the application of information technology and automation of modern agriculture in the production of non-psychoactive medicinal cannabis. Provide basis for the cultivation and wide application of new non-psychoactive medicinal cannabis varieties with high quality and high yield.

At present,China manages cannabis into industrial and medical types. Industrial cannabis( THC<0. 3%) is grown for fiber and seed,while medical cannabis( THC>0. 3%) is prohibited from being planted and used. In recent years,breakthroughs have been made in the applications for a variety of fields of CBD,a non-psychoactive cannabinoid of Cannabis. However,China made a minimal contribution to this international research hotspot,mainly due to the outdated way of classification on cannabis. Here we reviewed the medicinal use history of cannabis,achievements in the study of Cannabis germplasm,and first proposed the three-level classification of management: psychoactive medicinal cannabis( THC>0. 3%),non-psychoactive medicinal cannabis( THC<0. 3%,high CBD)and industrial cannabis( THC<0. 3%,for fiber and seed,low CBD). Based on summarizing the research progress of the non-psychoactive medicinal cannabis,four key research strategies of breeding,sex control,plant factory,and synthetic biology are proposed.

Introduction: Since endocannabinoids have been implicated in migraine pathophysiology, we conducted a randomized, controlled clinical trial to test the effects of a 12-week aerobic exercise intervention on plasma anandamide (AEA) and its relation with clinical, psychological, and cardiorespiratory outcomes. Materials and Methods: Episodic migraine patients taking no preventive drugs and nonheadache individuals were recruited from Hospital São Paulo and a tertiary headache clinic between March 2012 and March 2015. Participants were randomly assigned to receive aerobic exercise or enter the waitlist. Primary outcome was changes in plasma AEA; secondary outcome was number of days with migraine/month; and other clinical variables, mood scores, and cardiorespiratory fitness were chosen as tertiary outcomes. Measurements were taken on headache-free days. Data were analyzed by generalized linear models. Discussion: Fifty participants concluded the study (mean±SD age=36.2±10.9, and BMI=26.5±4.5). The plasma AEA reduced in migraine exercise (p<0.05) and control exercise groups (p<0.01). The number of days with migraine (p<0.01), migraine attacks (p<0.05), and abortive medication used (p<0.05) reduced in the migraine exercise group, whereas cardiorespiratory fitness increased in migraine exercise and control exercise groups (both p<0.05). Anxiety, depression, anger, and fatigue scores improved in the migraine exercise group (p<0.05 for all). Significant correlations between reduction in abortive medication used and cardiorespiratory fitness (r=-0.81 p<0.001), and reduced AEA (r=0.68 p<0.05) were found. Conclusions: This study suggests that peripheral AEA metabolism may be partly linked to the clinical and cardiorespiratory benefits of regular aerobic exercise in migraine patients. Trials registration: #NCT01972607.

Introduction: Gilles de la Tourette syndrome (GTS) is a neuropsychiatric disorder that is characterized by motor and vocal tics and psychiatric comorbidities, including attention deficit/hyperactivity disorder (ADHD) and obsessive-compulsive behavior/disorder (OCB/OCD). From anecdotal reports and preliminary controlled studies, it is suggested that cannabis-based medicine (CBM) may improve tics and comorbidities in adults with GTS. This study was designed to further investigate efficacy and safety of CBM in GTS and specifically compare effects of different CBM. Materials and Methods: First, we performed a retrospective data analysis including all those adult patients seen at our clinic, who had used CBM for the treatment of GTS at some time. All these patients were asked to complete an online survey (second study part) to receive more detailed data about treatment with CBM. Results: From medical records, we identified 98 patients who had used CBM (most often street cannabis followed by nabiximols, dronabinol, medicinal cannabis) for the treatment of GTS: Of the 38 patients who were able to judge, 66% preferred treatment with medicinal cannabis, 18% dronabinol, 11% nabiximols, and 5% street cannabis. Altogether, CBM resulted in a subjective improvement of tics (of about 60% in 85% of treated cases), comorbidities (55% of treated cases, most often OCB/OCD, ADHD, and sleeping disorders), and quality of life (93%). The effects of CBM appear to persist in the long term. Adverse events occurred in half of the patients, but they were rated as tolerable. Dosages of all CBM varied markedly. Patients assessed cannabis (with a preference for tetrahydrocannabinol [THC]-rich strains) as more effective and better tolerated compared with nabiximols and dronabinol. These data were confirmed by results obtained from the online survey (n=40). Conclusion: From our results, it is further supported that CBM might be effective and safe in the treatment of tics and comorbidities at least in a subgroup of adult patients with GTS. In our sample, patients favored THC-rich cannabis over dronabinol and nabiximols, which might be related to the entourage effect of cannabis. However, several limitations of the study have to be taken into considerations such as the open uncontrolled design and the retrospective data analysis.

Background: There is variability in the reported Δ9-tetrahydrocannabinol (THC) and 11-hydroxy-tetrahydrocannabinol (11-OH-THC) pharmacokinetic (PK) and pharmacodynamic (PD) parameters between studies and there is limited investigation into how the presence of food or sex affect these parameters. In this study, we examined the PK and PD parameters of an encapsulated THC extract and its major active metabolite, 11-OH-THC, under different fed states. Methods: The study was a single-dose, randomized, double-blinded, four-way crossover investigation. THC capsules (1 or 2×5 mg) were administered to 28 healthy adults (13 females: 15 males) under a fasted condition or after a high-fat meal. Blood samples were collected and PK parameters were determined through noncompartmental analysis. Adverse events (AEs), cognitive function (through completion of digit symbol substitution tests), blood pressure, and heart rate were also recorded. Results: The presence of high-fat food significantly enhanced time to peak plasma concentration (Tmax) and area under the curve (AUC0-24) for both THC and 11-OH-THC and reduced THC's apparent volume of distribution (Vz/F) and apparent clearance (Cl/F). Females had a significantly greater peak plasma concentration (Cmax) compared with males after 5 mg THC in a fasted state. No cardiovascular or cognitive effects and only mild AEs (somnolence, fatigue, and euphoric mood) were reported. Conclusion: These findings may help to inform the guidelines provided by governing health bodies on the effects of cannabis, such as time to onset and duration of action, and aid health care practitioners in their prescribing practices. Furthermore, the doses used in this study are safe to consider for future interventional studies in disease conditions where THC has been shown to have therapeutic efficacy.

Introduction: The cannabinoid type 1 (CB1) receptor and cannabinoid type 2 (CB2) receptor are widely expressed in the body and anandamide (AEA) and 2-arachidonoylglycerol (2-AG) are their best characterized endogenous ligands. The diacylglycerol lipases (diacylglycerol lipase alpha and diacylglycerol lipase beta) not only synthesize essentially all the 2-AG in the body but also generate other monoacylglycerols, including 2-linoleoylglycerol (2-LG). This lipid has been proposed to modulate endocannabinoid (eCB) signaling by protecting 2-AG from hydrolysis. However, more recently, 2-LG has been reported to be a CB1 antagonist. Methods: The effect of 2-LG on the human CB1 receptor activity was evaluated in vitro using a cell-based reporter assay that couples CB1 receptor activation to the expression of the β-lactamase enzyme. Receptor activity can then be measured by a β-lactamase enzymatic assay. Results: When benchmarked against 2-AG, AEA, and arachidonoyl-2'-chloroethylamide (a synthetic CB1 agonist), 2-LG functions as a partial agonist at the CB1 receptor. The 2-LG response was potentiated by JZL195, a drug that inhibits the hydrolysis of monoacylglycerols. The 2-LG response was also fully inhibited by the synthetic CB1 antagonist AM251 and by the natural plant derived antagonist cannabidiol. 2-LG did not potentiate, and only blunted, the activity of 2-AG and AEA. Conclusions: These results support the hypothesis that 2-LG is a partial agonist at the human CB1 receptor and capable of modulating the activity of the established eCBs.

As countries progressively embrace the legalization of both medicinal and recreational cannabis, there remains a significant knowledge gap when it comes to the perioperative uses of cannabis, as well as the management of cannabis users. This review summarizes the information available on the subject based on existing published studies. Articles outlining the physiological changes occurring in the human body during acute and chronic use of cannabis (outside the context of anesthesia) are also taken into consideration as understanding these changes allows a more calculated approach to better anticipate patients' needs in the perioperative setting. Common questions facing the anesthesiologist at each phase of the perioperative period will be addressed and a systematic approach to the effect of cannabinoids on various organ systems will also be presented. Issues unique to cannabis use such as cannabis withdrawal syndrome and alterations in post-operative pain processing will also be discussed. To date, the number of studies available for guidance is small and study designs are markedly heterogenous, if not limited, making conclusions challenging. While the currently available information can assist in making decisions, further studies of larger scale are eagerly anticipated to help guide future patient care.

To summarize the history and evolution of cannabis use and policies and to review current therapeutic uses, safety, and the central role pharmacists can play.Cannabis regulation and use have evolved over the centuries and are becoming more widely accepted, with over two-thirds of states in the United States having an approved cannabis program. However, changing policy and a paucity of controlled clinical trials has led to questions on the safety and effectiveness of cannabinoid therapies. Although there are conditions for which cannabinoids may be helpful, potential contraindications, adverse effects, and drug-drug interactions should be taken into account.Pharmacists are in a unique position based on their accessibility, knowledge, and skills to guide product selection, dosing, and discuss drug interactions and adverse effects to educate patients on safe cannabis use, whether it be delta-9-tetrahydrocannabinol, cannabidiol, or a combination thereof. Pharmacists and pharmacy organizations, moreover, should advocate for an integral role in the medical cannabis movement to ensure patient safety and evaluate cannabinoid pharmacology, pharmacokinetics, drug-drug interactions, safety, and efficacy through rigorous investigations.

Dravet syndrome is an intractable pediatric epilepsy associated with SCN1A mutations. In addition to having a large seizure burden and a reduced lifespan, patients with Dravet syndrome also exhibit delays in reaching normal developmental milestones in attentional, emotional, and cognitive function. These developmental delays manifest in autistic-like social withdrawal and compulsive behavior. Additionally, cognitive impairments including deficits in sensorimotor processing and memory function are present. Several mouse models utilizing heterozygous deletion of Scn1a (Scn1a+/- mice) have been generated that recapitulate many aspects of Dravet syndrome. Studies in these mouse models of Dravet syndrome have characterized behavioral phenotypes in adult mice. In the present study, we characterized the behavioral phenotype of Scn1a+/- mice generated by targeted deletion of Scn1a exon 1 (Scn1atm1Kea) during adolescence. Identifying behavioral deficits in adolescent mice would more closely model the early onset of attentional, emotional, and cognitive delays observed in patients with Dravet syndrome. The behaviors of adolescent Scn1a+/- and wildtype (WT) mice were compared across several behavioral domains. We assessed motor function (open-field test), sociability and social recognition memory (three-chambered social preference and social interaction tests), memory function (novel object recognition, Barnes maze, fear conditioning paradigm), anxiety-related behavior (elevated plus maze and open-field thigmotaxis), startle reflex and sensorimotor gating (prepulse inhibition of startle (PPI) tests), and repetitive compulsive behavior (marble burying test). Adolescent Scn1a+/- mice exhibited normal locomotor activity, marble burying behavior, sociability, and sensorimotor gating. However, adolescent Scn1a+/- mice displayed increased anxiety-related thigmotactic behavior, atypical fear expression, blunted acoustic startle responses, and impaired social recognition and spatial memory. Our results show that Scn1a+/- mice display various behavioral impairments during adolescence, which provides a foundation for testing early intervention therapies targeting developmental delays modeled in Dravet syndrome mice.

The deleterious impact of low mental well-being, and higher levels psychological symptoms (collectively well-being), on concurrent and prospective health outcomes has elsewhere been demonstrated. Further, variables such as conurbation and deprivation have been found to be related to mental and physical heath. This study used data from a longitudinal study to examine which demographic predicted well-being scores, and how scores on these constructs were related to six health-related outcomes. Participants were adolescents (N = 4,956; Male = 2376[48%]), from 72 High Schools in Northern Ireland. Three waves of data were gathered on mental well-being, psychological symptoms, subjective life expectancy (living to age 35 and age 75 years), self-rated health, frequency of physical exercise, and lifetime use of cigarettes and cannabis. Results showed that both well-being scores were significantly associated with gender cross-sectionally, but demographic variables did not predict changes in well-being longitudinally. Both well-being measures were significantly associated with health outcomes cross-sectionally, with mental well-being (over time) predicting life subjective life expectancy, self-rated health, and addictive behaviors, while psychological symptoms (over time) predicted the former two, but not addictive behaviors. Overall, the relationship between mental well-being, psychological symptoms, and the health outcomes assessed, was small in terms of effect size.

Cannabis is the most widely used illicit substance by Australian young people, including those engaged with youth alcohol and other drug (AOD) systems. While recreational cannabis use in young people may be a developmental activity for some, for others, this usage becomes regular and be associated with poorer long term outcomes. This study reports on the rates of cannabis use and co-existing psychosocial complexity factors in the Youth Needs Census (2013 and 2016) where workers report on all clients in the youth AOD system, a cohort considered highly vulnerable.Data was examined for two rounds of data collection for the Youth Needs Census, including 823 youth AOD service engaged young people in 2016 and 1000 AOD service engaged young people in 2013, to identify usage rates, psychosocial outcomes, and changes over time.Daily use of cannabis alone significantly exceeded daily usage rates for methamphetamines, alcohol, and cannabis used alongside other substances. Daily cannabis use was significantly associated with mental health problems, employment problems, education problems, family problems, and housing problems. Daily cannabis use was associated with most psychosocial complexity factors to the same extent as daily methamphetamine use and daily alcohol use, with daily cannabis users only showing lower incidence of the drug-related harm measure. Notably, daily cannabis use also increased from 2013 (47.5%) to 2016 (54.2%).It is imperative that the number of individuals using cannabis is considered alongside the severity of harm when assessing the social impact of this substance. Within cannabis users engaged with the youth AOD system, who often have high levels of psychosocial complexity, cannabis is used daily by a large proportion of these youths and may play a role in negatively impacting their lives.

Recent legalization of therapeutic and recreational cannabis use makes it imperative to have an insight into odds and trends in young-onset stroke-related hospitalizations among cannabis users (18-49 years).The National Inpatient Sample dataset (2007-2014) was utilized to assess national trends, odds of young-onset stroke-related hospitalizations, and outcomes among cannabis users vs. nonusers using provided discharge weights, strata, and cluster design. The rates are described per 100,000 hospitalizations among cannabis users and non-users.A total of 3,307,310 hospitalizations were identified among young adults with current or previous cannabis use. Of these, 34,857 (1.1%) were related to young-onset stroke. A relative increase of 13.92% (553 in 2007 to 630 in 2014; ptrend < 0.001) in young-onset stroke admissions was reported among cannabis users. The odds of any stroke (OR 1.16, 95% CI 1.14-1.19, p < 0.001) and acute ischemic stroke (OR 1.41, 95% CI 1.31-1.51, p < 0.001) hospitalizations were considerably higher among cannabis users as compared to nonusers. In-hospital mortality rates were increasing (3.7% to 4.3%) among cannabis users whereas decreasing (7.7% to 5.9%) in nonusers from 2007 to 2014 (ptrend < 0.001). The mean length of stay and the hospitalization charges showed increasing trends in cannabis-related young-onset stroke admissions. There was an increasing trend in young-onset stroke admissions among male cannabis users (578 to 701; ptrend < 0.001) but not among females (516 to 457; ptrend = 0.14). The maximum rise in the young-onset stroke-related admissions was seen in African Americans (743 to 996; ptrend < 0.001).We identified rising trends and higher risk (16% higher of overall young-onset stroke, 41% higher of acute ischemic stroke) of stroke-related hospitalizations and worse outcomes among cannabis users aged 18-49 years from 2007 to 2014.

Cannabis plant has the scientific name called Cannabis sativa L. Cannabis plant has many species, but there are three main species including Cannabis sativa, Cannabis indica and Cannabis ruderalis. Over 70 compounds isolated from cannabis species are called cannabinoids (CBN). Cannabinoids produce over 100 naturally occurring chemicals. The most abundant chemicals are delta-9-tetrahydrocannabinol (THC) and Cannabidiol (CBD). THC is psychotropic chemical that makes people feel "high" while CBD is nonpsychotropic chemical. However, cannabinoid chemicals are not found only in the cannabis plant, they are also produced by the mammalian body, called endocannabinoids and in the laboratory, called synthesized cannabinoids. Endocannabinoids are endogenous lipid-based retrograde neurotransmitters that bind to cannabinoid receptors, and cannabinoid receptor proteins that are expressed throughout the mammalian central nervous system including brain and peripheral nervous system. There are at least two types of endocannabinoid receptors (CB1 and CB2) which are G-protein coupled receptors. CB1 receptors are particularly abundant in the frontal cortex, hippocampus, basal ganglia, hypothalamus and cerebellum, spinal cord and peripheral nervous system. They are present in inhibitory GABA-ergic neurons and excitatory glutamatergic neurons. CB2 receptor is most abundantly found on cells of the immune system, hematopoietic cells and glia cells. CB2 is mainly expressed in the periphery under normal healthy condition, but in conditions of disease or injury, this upregulation occurs within the brain, and CB2 is therefore expressed in the brain in unhealthy states. Cannabis and cannabinoid are studied in different medical conditions. The therapeutic potentials of both cannabis and cannabinoid are related to the effects of THC, CBD and other cannabinoid compounds. However, the "high" effect of THC in cannabis and cannabinoid may limit the clinical use, particularly, the study on the therapeutic potential of THC alone is more limited. This review emphasizes the therapeutic potential of CBD and CBD with THC. CBD has shown to have benefit in a variety of neuropsychiatric disorders including autism spectrum disorder, anxiety, psychosis, neuropathic pain, cancer pain, HIV, migraine, multiple sclerosis, Alzheimer disease, Parkinson disease, Huntington disease, hypoxic-ischemic injury and epilepsy. CBD is generally well tolerated. Most common adverse events are diarrhea and somnolence. CBD also shows significantly low abuse potential.

The legalization of non-medical cannabis in 2018 may have important implications for tobacco use in Canada. There is a risk of re-normalizing tobacco use with co-use of tobacco and cannabis introducing nontobacco users to tobacco. Co-use is the use of both substances by the same individual at the same time or on different occasions, as well as mixed together. This study assessed the prevalence of co-use and mixing of tobacco and cannabis among Ontario adults and the characteristics of the users.Data from the 1996 to 2017 cycles of the Centre for Addiction and Mental Health Monitor (n=4,481) were used to examine trends in prevalence and the proportion of Ontario adults co-using and mixing tobacco and cannabis. Logistic regression was used to study associations between user characteristics and co-use and mixing.Co-use of cigarettes and cannabis among cannabis users declined from 59.8% in 1996 to 41.7% in 2017. Past-year e-cigarette use was the only predictor of co-use. From 2015 to 2017, 31.1% (95% CI 27.0, 35.9) of Ontario adults who used cannabis reported mixing it with tobacco in the past year. Being white, past-year e-cigarette use, having moderate or high nicotine dependence, and having moderate or high risk for cannabis problems were significant predictors of mixing among cannabis users.Given the well-established negative health effects associated with tobacco use, alongside a growing evidence base for negative health effects of cannabis smoking, co-use and mixing could pose a considerable public health concern in the context of legalization.

[This corrects the article DOI: 10.1089/can.2016.0028.].

Risk for substance use disorders (SUDs) is hypothesized to include behavioral disinhibition, a genetically mediated inability to inhibit or regulate behavior given task demands or motivational drives. In the present study, we examined developmental trajectories of multiple indicators of behavioral disinhibition assessed from preadolescence into early adulthood among individuals with versus without alcohol, tobacco, and cannabis use disorders. Participants were a population-based sample of 1512 male and female twins from the Minnesota Twin Family Study, prospectively assessed at ages 11, 14, 17, 20, and 24. Multimodal indicators of behavioral disinhibition included measures of executive function (visuospatial working memory accuracy, antisaccade task performance) and mother- and self-reported trait disconstraint. Multilevel modeling analyses that accounted for the repeated measures and nested nature of the twin family data were used to examine premorbid (age 11) indicators of executive function and trait disconstraint prior to the onset of any SUD symptoms, as well as changes from preadolescence into early adulthood (ages 11 to 24). Premorbid deviations evident at age 11 among individuals who subsequently developed SUDs included poorer performance on the visuospatial working memory test and higher levels of trait disconstraint. In addition, individuals with SUDs did not demonstrate developmentally normative improvements in inhibitory control (i.e., antisaccade performance did not improve) or in their levels of trait disconstraint. We conclude that these deviations in both neurocognitive and dispositional correlates of behavioral disinhibition precede onset of SUDs and may confer risk for their development, and in addition, problematic substance use may exacerbate preexisting deviations and interfere with normative developmental trajectories of executive function and trait disconstraint, with deleterious consequences for functioning.

Alcohol, tobacco and unregulated substance use contributes to the global burden of disease. Admission to hospital provides an opportunity to screen patients for substance use and offer interventions.To determine the prevalence and nature of substance use and treatment as well as interest in harm reduction among inpatients from four hospitals in the City of Tshwane, South Africa.In a cross-sectional study, sociodemographic and substance use data were collected from 401 patients using the World Health Organization's Alcohol, Smoking and Substance Involvement Screening Test. Demographic characteristics were analysed using descriptive statistics. Bivariate and multivariate analyses of moderate- to high-risk tobacco and unregulated substance use in relation to demographic characteristics were also done.Most patients were South African (88%) and black African (79%), over half were female (57%), and they were relatively young (median age 38 years). Most (82%) lived in formal housing. Over half (56%) had completed high school, and 33% were formally employed. Bivariate analysis found substance use-related admission to be higher where scores for tobacco and unregulated substance use were moderate to high (13% v. 0.3%, p<0.05). A notably higher (p<0.1) proportion of participants with no/low tobacco and unregulated substance use had completed high school, were employed and were cohabiting/married compared with those with moderate to high scores. Across the hospitals, 32% (129/401) of the participants had moderate- to high-risk use of at least one substance: tobacco (28%, 111/401), alcohol (10%, 40/401), cannabis (7%, 28/401), opioids (2%, 9/401) and sedatives (2%, 9/401). Of these 129 participants, 10% had accessed professional help, many (67%, 78/129) wanted to learn more about harm reduction, and most (84%, 108/129) said that they were willing to participate in a community-based harm reduction programme. Multivariate analysis found moderate- to high-risk tobacco and unregulated substance use to be positively associated with male sex (adjusted odds ratio (aOR) 7.9, 95% confidence interval (CI) 2.9 - 21.5), age <38 years (aOR 3.3, 95% CI 1.2 - 8.9), moderate- to high-risk alcohol use (aOR 3.1, 95% CI 1.1 - 8.4; p=0.027) and being admitted to Tshwane District Hospital (aOR 3.6, 95% CI 1.1 - 12.2). It was negatively associated with employment (aOR 0.2, 95% CI 0.1 - 0.6).Moderate- to high-risk substance use is an undetected, unattended comorbidity in the hospital setting in Tshwane, particularly among young, single, unemployed men. Clinicians should identify and respond to this need. Further research is required on the implementation of in-hospital substance use screening and treatment interventions.

Cannabis is the most commonly used illicit drug in the world. However, because of a changing legal landscape and rising interest in therapeutic utility, there is an increasing trend in (long-term) use and possibly cannabis impairment. Importantly, a growing body of evidence suggests that regular cannabis users develop tolerance to the impairing, as well as the rewarding, effects of the drug. However, the neuroadaptations that may underlie cannabis tolerance remain unclear. Therefore, this double-blind, randomized, placebo-controlled, cross-over study assessed the acute influence of cannabis on the brain and behavioral outcomes in two distinct cannabis user groups. Twelve occasional and 12 chronic cannabis users received acute doses of cannabis (300-μg/kg delta-9-tetrahydrocannabinol) and placebo and underwent ultrahigh field functional magnetic resonance imaging and magnetic resonance spectroscopy. In occasional users, cannabis induced significant neurometabolic alterations in reward circuitry, namely, decrements in functional connectivity and increments in striatal glutamate concentrations, which were associated with increases in subjective high and decreases in performance on a sustained attention task. Such changes were absent in chronic users. The finding that cannabis altered circuitry and distorted behavior in occasional, but not chronic users, suggests reduced responsiveness of the reward circuitry to cannabis intoxication in chronic users. Taken together, the results suggest a pharmacodynamic mechanism for the development of tolerance to cannabis impairment, of which is important to understand in the context of the long-term therapeutic use of cannabis-based medications, as well as in the context of public health and safety of cannabis use when performing day-to-day operations.

While recent research has shown that cannabis access laws can reduce the use of prescription opioids, the effect of these laws on opioid use is not well understood for all dimensions of use and for the general United States population. Analyzing a dataset of over 1.5 billion individual opioid prescriptions between 2011 and 2018, which were aggregated to the individual provider-year level, we find that recreational and medical cannabis access laws reduce the number of morphine milligram equivalents prescribed each year by 11.8 and 4.2 percent, respectively. These laws also reduce the total days' supply of opioids prescribed, the total number of patients receiving opioids, and the probability a provider prescribes any opioids net of any offsetting effects. Additionally, we find consistent evidence that cannabis access laws have different effects across types of providers, physician specialties, and payers.

To provide an up-to-date summary of the benefits and harms of cannabis-based products for epilepsy in children.We updated our earlier systematic review, by searching for studies published up to May 2019. We included randomized controlled trials (RCTs) and non-randomized studies (NRS) involving cannabis-based products administered to children with epilepsy. Outcomes were seizure freedom, seizure frequency, quality of life, sleep, status epilepticus, death, gastrointestinal adverse events, and emergency room visits.Thirty-five studies, including four RCTs, have assessed the benefits and harms of cannabis-based products in pediatric epilepsy (12 since April 2018). All involved cannabis-based products as adjunctive treatment, and most involved cannabidiol. In the RCTs, there was no statistically significant difference between cannabidiol and placebo for seizure freedom (relative risk 6.77, 95 % confidence interval [CI] 0.36-128.38), quality of life (mean difference [MD] 0.6, 95 %CI -2.6 to 3.9), or sleep disruption (MD -0.3, 95 %CI -0.8 to 0.2). Data from both RCTs and NRS suggest that cannabidiol reduces seizure frequency and increases treatment response; however, there is an increased risk of gastrointestinal adverse events.Newly available evidence supports earlier findings that cannabidiol probably reduces the frequency of seizures among children with drug-resistant epilepsy.CRD42018084755.

Although the associations between first-episode psychosis (FEP) and metabolic abnormalities on one side, and childhood trauma (CT) and risk of developing psychosis on the other are both well established, evidence on the relationship between CT and metabolic dysregulation in terms of abnormal glucose metabolism is very limited. We tested whether, already at illness onset, FEP patients with a history of CT show dysregulation of a broad range of glucose metabolism markers. In particular, in 148 FEP patients we evaluated serum concentrations of c-peptide, insulin, plasminogen-activator-inhibitor-1 (PAI-1), resistin, visfatin, glucagon, glucagon-like peptide-1 (GLP-1), gastric-inhibitor-peptide (GIP), leptin, and ghrelin. We also assessed CT with the Childhood Experience of Care and Abuse Questionnaire, and stressful life events (SLEs) with a semi-structured interview. Psychopathology, cannabis and tobacco habits, Body Mass Index (BMI) were recorded. Serum concentrations of markers were analyzed from peripheral blood. Ninety-five patients (56 % males, mean age 29.5) reported CT. Multivariate models showed that CT is associated only with the concentrations of c-peptide and insulin after adjusting for age, sex, BMI and SLEs. FEP patients who had experienced CT showed higher c-peptide and insulin serum concentrations. Our study reports that CT might be associated with the metabolic abnormalities in the first stage of psychosis, suggesting that a thorough anamnestic evaluation at psychosis onset that would include the history of CT could be helpful for clinicians in order to implement early programmes of healthy lifestyle education and to guide choice of therapeutic interventions for trauma.

New Zealand may be the next national jurisdiction where non-medical cannabis use and supply will be legalized. While the current New Zealand government's plans for possible cannabis legalization were rather unclear for some time, initial details on proposed key parameters (for example, age limits, production and supply modes, use restrictions) of a possible cannabis legalization framework have recently emerged. We provide initial basic examination and contextualization of the proposal's select key details, both vis-a-vis select legalization frameworks as they exist in other jurisdictions as well as in reference to key parameters of policy and controls governing other legal psychoactive substances in New Zealand. Overall, the proposed framework for non-medical cannabis legalization in New Zealand resembles other (e.g., Canada's) legalization models in spirit and main proposed regulations. There are, however, several proposed regulation elements where questions regarding both feasibility and/or policy coherence concerning other psychoactive substance areas arise and likely to lead to challenges or problems in practice. Evidently, substantially more thinking, consideration and development need to be invested towards a more complete and workable public health-oriented framework and roadmap for cannabis legalization in New Zealand. Furthermore, possible cannabis legalization reforms hinge on the successful outcome of a public referendum (in late 2020), adding the acute need for substantive pre-referendum public education as well as overall extrinsic uncertainty regarding the prospects of actual and material policy change.

Driving under the influence of cannabis (DUIC) is a public health concern, and data are needed to develop screening and prevention tools. Measuring the level of intoxication that cannabis users perceive as safe for driving could help stratify DUIC risk. This study tested whether intoxication levels perceived as safe for driving predicted past-month DUIC frequency. Online survey data were collected in 2017 from a national sample of n = 3010 past-month cannabis users with lifetime DUIC (age 18+). Respondents indicated past-month DUIC frequency, typical cannabis intoxication level (1-10 scale), and cannabis intoxication level perceived as safe for driving (0-10 scale). Approximately 24%, 38%, 13%, and 24% of respondents engaged in DUIC on 0, 1-9, 10-19, and 20-30 days respectively in the past month. Among these four DUIC frequency groups, median typical intoxication varied little (5-6), but median intoxication perceived as safe for driving varied widely (3-8). Higher intoxication levels perceived as safe for driving corresponded to frequent DUIC (Spearman's rho: 0.46). For each unit increase in intoxication level perceived as safe for driving, the odds of past-month DUIC increased 18% to 68% (multinomial logistic regression odds ratio - MOR1-9 days: 1.18, 95% CI: 1.13-1.23; MOR10-19 days: 1.40, 95% CI: 1.30-1.50; MOR20-30 days: 1.68, 95% CI: 1.57-1.80). In this targeted sample of past-month cannabis users, DUIC frequency varied widely, but daily/near-daily DUIC was common (24%). Measuring intoxication levels perceived as safe for driving permits delineation of past-month DUIC frequency. This metric has potential as a component of public health prevention tools.

The unpredictable physiologic and pharmacologic effects of synthetic cannabinoids (SCs) are continuously changing as the chemical structure of SCs evolve to avoid classification as a Schedule I drug under the Controlled Substances Act in the U.S. This results in unpredictable pharmacologic effects and subsequent sequelae. Little is known about national or regional trends of SC clusters. The objective of this study is to investigate trends in SC exposure using emergency department (ED) syndromic data.We analyzed ED syndromic data to detect quarterly trends from January 2016 through September 2019 for SC-related exposures within 59 jurisdictions in 47 states by U.S. region. Pearson chi-square tests detected quarter-to-quarter changes and Joinpoint regression assessed trends over time.From January 2016 to September 2019, 21,714 of 303.5 million ED visits involved suspected SC exposures. Nationally, SC-related exposures decreased by 1.9 % (p = .04) on average per quarter, yet exposures increased in the Midwest by 6.3 % (p = .002) and in the Northeast by 3.2 % (p = .03) on average per quarter, and decreased on average per quarter by 7.7% (p ≤ .001) in the Southeast and 11.4 % in the West (p ≤ .001). Known SC exposures that may align with clusters were identified in quarter-to-quarter monitoring.Only a small proportion of ED visits were related to suspected SC exposure. Although we did identify a small decrease in national SC exposures, there was wide variation by region. Additional efforts are needed to understand variation and to develop prevention and response strategies.

Cannabis extracts like marijuana have the highest consumption rate worldwide. Yet, their societal acceptance as recreational and therapeutic drugs could represent a serious hazard to female human reproduction, because cannabis ingredients [termed (phyto)cannabinoids] can perturb an endogenous system of lipid signals known as endocannabinoids. Accumulated evidence on animal models and humans has demonstrated a crucial role of these endogenous signals on different aspects of female reproduction, where they act through an ensamble of proteins that synthesize, transport, degrade and traffic them. Several reports have recently evidenced the potential role of endocannabinoids as biomarkers of female infertility for disease treatment and prevention, as well as their possible epigenetic effects on pregnancy. The purpose of this review is to provide an update of data collected in the last decade on the effects of cannabinoids and endocannabinoids on female reproductive events, from development and maturation of follicles and oocytes, to fertilization, oviductal transport, implantation and labor. In this context, a particular attention has been devoted to the ovary and the production of fertilizable oocytes, because recent studies have addressed this hot topic with conflicting results among species.

Illicit psychoactive substance (IPAS) use can lead to a number of respiratory complications, including acute eosinophilic pneumonia (AEP). Systematic literature review of data on AEP in IPAS users (cannabis, cocaine, heroin and amphetamine). Of two cases of cannabis and tobacco users reported to have developed AEP, one, a teenage15 year old boy presented with acute respiratory distress syndrome (ARSD) which necessitated extracorporeal membrane oxygenation (ECMO). Five cases of AEP in cocaine smokers (crack) are reported, one of which was fatal. The patient presented with acute pulmonary edema and ARDS which progressed to ventricular fibrillation and asystole. A 24-year-old woman presented with AEP after repeated inhalation of heroin. Finally, a case of an amphetamine abuser who developed AEP and ARDS after amphetamine inhalation is reported. The time between the first IPAS use and admission in cases reported ranged from 7 days to 4 years, while time between the last IPAS use and admission was short (less than 15 days). IPAS use must be sought in case of AEP, especially in young adults, and practitioners must advise and help users to stop their consumption.

Endocannabinoids are natural lipid molecules whose levels are regulated by specific biosynthetic and degradative enzymes. They bind to and activate two main cannabinoid receptors type 1 (CB1) and type 2 (CB2), and together with their metabolizing enzymes form the "endocannabinoid system" (ECS). In the last years, the relevance of endocannabinoids (eCBs) as critical modulators in various aspects of male reproduction has been pointed out. Mammalian male germ cells, from mitotic to haploid stage, have a complete ECS which is modulated during spermatogenesis. Compelling evidence indicate that in the testis an appropriate "eCBs tone", associated to a balanced CB receptors signaling, is critical for spermatogenesis and for the formation of mature and fertilizing spermatozoa. Any alteration of this system negatively affects male reproduction, from germ cell differentiation to sperm functions, and might have also an impact on testicular tumours. Indeed, most of testicular tumours develop during early germ-cell development in which a maturation arrest is thought to be the first key event leading to malignant transformation. Considering the ever-growing number and complexity of the data on ECS, this review focuses on the role of cannabinoid receptors CB1 and CB2 signaling in male germ cells development from gonocyte up to mature spermatozoa and in the induction of epigenetic alterations in these cells which might be transmitted to the progeny. Furthermore, we present new evidence on their relevance in testicular cancer.

Recent increases in maternal cannabis use, in combination with rapidly changing cannabis policies in the United States, pose a unique threat to maternal and child health. To date, 33 states and the District of Columbia (D.C.) have legalized medicinal cannabis, and 11 states and D.C. have legalized recreational cannabis. Many other states have decriminalized cannabis and are considering legalization. Recent data suggest that maternal cannabis use is increasing. Maternal cannabis use in the postpartum period, including breastfeeding women, may contribute to negative health outcomes in young children. Perinatal health professionals should work collaboratively to safeguard maternal and child health outcomes from potential adverse health effects of cannabis use. To that end, we highlight the critical role International Board Certified Lactation Consultants® (IBCLCs®) could play in postpartum management of cannabis use. IBCLCs have direct access to a large number of women shortly after delivery and throughout the postpartum period. They are an extremely well-positioned, but arguably underutilized, and are potential partners for postpartum management of cannabis use. Given the rapport IBCLCs frequently develop with their patients, these mothers may be especially willing to disclose cannabis use and be receptive to education and advice to quit cannabis use while breastfeeding. As such, we propose that the role of IBCLCs be promoted to support families with nonpunitive education about the potential risks, advice to not use cannabis while breastfeeding, and timely referral for treatment, when needed. This approach holds promise for improving the health and quality of life for breastfeeding women and their infants.

Cannabis use is typically initiated during adolescence, and different studies suggest that adolescent cannabinoid exposure may increase the risk for drug addiction in adulthood.This study investigated the effects of adolescent exposure to the main psychoactive component of cannabis, ∆9-tetrahydrocannabinol (THC), in the reinforcing properties of nicotine in adult male mice. Possible alterations in relapse to nicotine-seeking behaviour in adult animals due to THC adolescent exposure were also evaluated.Adolescent mice were exposed to escalating doses of THC from PND35 to PND49. When mice reached adulthood (PND70), surgical procedures were applied for further behavioural evaluation. Nicotine self-administration sessions were conducted consecutively for 10 days. Following extinction, mice were tested for cue- and stress-induced reinstatement of nicotine-seeking behaviour.Adolescent THC treatment did not modify acquisition and extinction of nicotine self-administration in adulthood. Moreover, THC exposure did not alter relapse to nicotine seeking induced by stress or nicotine-associated cues.These results suggest that a history of exposure to THC during adolescence under these particular conditions does not modify the reinforcing effects and seeking behaviour of nicotine in the adult period.

Cannabis use disorder (CUD) is the most common illicit substance use disorder in the United States and is related to a range of functional impairment. CUD is associated with comorbid mental health disorders and other substance use disorders, compounding impairment from either type of disorder alone. U.S. military veterans also experience CUD at high rates; however, less is known about comorbidity and its impact on service utilization among veterans. Better understanding of comorbidity in this group is important, given that the Veterans Health Administration is the largest U.S. healthcare provider and is uniquely positioned to potentially address the challenges of comorbid CUD. The current study aimed to examine rates of comorbidity among veterans with CUD and the impact of comorbidity on mental health service utilization. Data were obtained through national Veterans Health Administration administrative and clinical records from 2010 to 2016. 79.1% of veterans with CUD were also diagnosed with a mental health disorder, and 76.8% were diagnosed with another substance use disorder. Overall, veterans with CUD and a comorbid mental health disorder used more individual psychotherapy than those with CUD alone. These findings suggest that CUD among veterans is rarely diagnosed independent of other disorders and that comorbidity is associated with greater mental healthcare utilization. Improved screening for CUD and integration of its treatment within current models of care may be important to consider in large healthcare systems.

With the expansion of medical and recreational legalization of cannabis, there is growing interest in cannabis use by people with multiple sclerosis (MS). Research supports that cannabis relieves MS-related pain and spasticity, two common symptoms of MS. However, there is limited information available about cannabis use in people with MS across the United States and Canada.1,015 people with MS in the US and Canada participated in an informational webinar on cannabis for the control of MS symptoms. Attendees were presented with three questions about their use of cannabis for MS symptoms and their knowledge of the medical legality of cannabis in their state. Demographics and MS characteristics were obtained from webinar registration. The legality of cannabis (not legal, legal for medical use only, and legal for recreational and medical use) and the number of years since medical legalization at the time of this webinar were determined for all states. Using logistic regression, we analyzed associations between individual characteristics (demographics, disease severity and legal status), cannabis use, and knowledge of legality.Of the 1,015 webinar registrants, 54% (n = 548) answered the question, "Have you used marijuana in the past year to help control your MS symptoms?" and were included in the analyses. Statistically significant associations were seen between cannabis use and local legal status of cannabis (recreational vs. not legal: OR 4.55, 95% CI: [1.70-12.14], p = 0.002), years since medical legalization of cannabis (for each year since legalization: OR 1.06, 95% CI: [1.02 - 1.10], p = 0.004), disease severity (severe vs. mild disability: OR 3.41, 95% CI: [1.23 - 9.46] p = 0.018) and gender (male vs. female: OR 2.33, 95% CI: [1.10-4.94], p = 0.027). Accuracy of knowledge of local cannabis legality was significantly associated with cannabis use in the past year (users vs. non-users: OR 2.52, p = 0.014), local legal status of cannabis (medical only vs. not legal: OR 0.30, p = 0.001; recreational vs. not legal: OR 4.98, p = 0.039), years since legalization of cannabis (for each increased year since legalization: OR 1.15, p < 0.001), and country of residence (Canada vs. USA: OR 0.42, p = 0.021).This study supports that cannabis use for MS symptoms is more common in states where cannabis laws are more permissive and where cannabis has been legal for longer, in those with more severe MS, and in men. Accurate knowledge of local cannabis legality is more common in those who report using cannabis for their MS in the past year. Those living in states where cannabis is legal for medical use only are less likely to be aware of legal status than those in either recreationally-legal or non-legal states, but awareness of legal status increases with time since medical legalization. Canadians are less likely than Americans to be accurate in their perception of the legal status of cannabis.

Eleven US states and Washington, DC, legalized recreational (adult use) cannabis. Seven states-Alaska, California, Colorado, Massachusetts, Nevada, Oregon, and Washington-allow cannabis sales. A public health concern is that exemptions in state or local smoke-free laws for public cannabis smoking or vaping will weaken smoke-free laws, expose the public to secondhand cannabis, and renormalize smoking.We describe the experience of the seven states and challenges faced in maintaining smoke-free laws. Using elements of a tobacco control framework, we identify best practices in cannabis regulation by comparing each state's smoke-free laws and allowances for public cannabis use. All states prohibit public cannabis use; two lack 100% smoke-free protections; one lacks vaping devices in its smoke-free law; three allow cannabis use in retailers; two allow cannabis use in social consumption lounges; and two allow cannabis use in tourism venues.States should close gaps in smoke-free laws and not expand where cannabis use is permitted to ensure public health.

Objectives. To use publicly accessible data from people who post to Twitter to rapidly capture and describe the public's recent experiences with cannabis.Methods. We obtained Twitter posts containing cannabis-related terms from May 1, 2018, to December 31, 2018. We used methods to distinguish between posts from social bots and nonbots. We used text classifiers to identify topics in posts (n = 60 861).Results. Prevalent topics of posts included using cannabis with mentions of cannabis initiation, processed cannabis products, and health and medical with posts suggesting that cannabis could help with cancer, sleep, pain, anxiety, depression, trauma, and posttraumatic stress disorder. Polysubstance use was a common topic with mentions of cocaine, heroin, ecstasy, LSD, meth, mushrooms, and Xanax along with cannabis. Social bots regularly made health claims about cannabis.Conclusions. Findings suggest that processed cannabis products, unsubstantiated health claims about cannabis products, and the co-use of cannabis with legal and illicit substances warrant considerations by public health researchers in the future.

Estimate the genetic and environmental influences on the relationship between onset of regular cannabis use and young adult insomnia.In a population-based twin cohort of 1882 twins (56% female, mean age = 22.99, SD = 2.97) we explored the genetic/environmental etiology of the relationship between onset of regular cannabis use and insomnia-related outcomes via multivariate twin models.Controlling for sex, current depression symptoms, and prior diagnosis of an anxiety or depression disorder, adult twins who reported early onset for regular cannabis use (age 17 or younger) were more likely to have insomnia (β = 0.07, p = 0.024) and insomnia with short sleep on weekdays (β = 0.08, p = 0.003) as young adults. We found significant genetic contributions for the onset of regular cannabis use (a2 = 76%, p < 0.001), insomnia (a2 = 44%, p < 0.001) and insomnia with short sleep on weekdays (a2 = 37%, p < 0.001). We found significant genetic correlations between onset of regular use and both insomnia (rA = 0.20, p = 0.047) and insomnia with short sleep on weekdays (rA = 0.25, p = 0.008) but no significant environmental associations between these traits.We found common genetic liabilities for early onset of regular cannabis use and insomnia, implying pleiotropic influences of genes on both traits.

While a known link between prenatal cannabis exposure and anencephaly exists, the relationship of prenatal cannabis exposure with neural tube defects (NTDs) generally has not been defined. Published data from Canada Health and Statistics Canada were used to assess this relationship. Both cannabis use and NTDs were shown to follow an east-west and north-south gradient. Last year cannabis consumption was significantly associated (P < .0001; cannabis use-time interaction P < .0001). These results were confirmed when estimates of termination for anomaly were used. Canada Health population data allowed the calculation of an NTD odds ratio) of 1.27 (95% confidence interval = 1.19-1.37; P < 10-11) for high-risk provinces versus the remainder with an attributable fraction in exposed populations of 16.52% (95% confidence interval = 12.22-20.62). Data show a robust positive statistical association between cannabis consumption as both a qualitative and quantitative variable and NTDs on a background of declining NTD incidence. In the context of multiple mechanistic pathways these strong statistical findings implicate causal mechanisms.

Medical cannabis is widely available in the USA and legalisation is likely to expand. Despite the increased accessibility and use of medical cannabis, physicians have significant knowledge gaps regarding evidence of clinical benefits and potential harms. We argue that primary care providers have an ethical obligation to develop competency to provide cannabis to appropriate patients. Furthermore, specific ethical considerations should guide the recommendation of medical cannabis. In many cases, these ethical considerations are extensions of well-established principles of beneficence and nonmaleficence, which indicate that providers should recommend cannabis only for conditions that have the strongest evidence base. Additionally, the contested status of cannabis in American culture raises specific issues related to shared decision-making and patient education, as well as continuing clinical education.

At the present time there are continuing debates on the legal status of cannabis in New Zealand. Many of these debates have not given sufficient consideration to evidence concerning cannabis-related harm, much of which has been gathered here in New Zealand by the Christchurch Health and Development Study (CHDS) and the Dunedin Multidisciplinary Health and Development Study (DMHDS). We present a summary of this evidence, and recommendations for a cautious path forward for changing cannabis laws in New Zealand that aims at reducing cannabis-related harm.

A novel plate-like nano-sorbent based on copper/cobalt/chromium layered double hydroxide was synthesized by a simple coprecipitation method. The synthesized nanoparticels were introduced into a stainless steel cartridge using a dry packing method. Then, the packed cartridge was introduced as a novel on-line "packed in-tube" configuration and followed by high performance liquid chromatography for the determination of trace amounts of ∆ 9-tetrahydrocannabinol from biological samples and cannabis leaves. The as-prepared sorbent exhibited long lifetime, good chemical stability, and high anion-exchange capacity. Several important factors affecting the extraction efficiency, such as extraction and desorption times, pH of the sample solution and flow rates of the sample and eluent solutions, were investigated and optimized. Under optimized conditions, this method showed good linearity for ∆ 9-tetrahydrocannabinol in the ranges of 0.09-500, 0.3-500, and 0.4-500 µg/L with coefficients of determination of 0.9999, 0.9991, and 0.9994 in water, serum and plasma samples, respectively. The inter- and intra-assay precisions (n = 3) were respectively in the ranges of 1.8-4.6% and 1.9-4.0% at three concentration levels of 10, 50, and 100 µg/L. The limits of detection were also in the range of 0.02-0.1 µg/L.

To identify key characteristics and habits of recreational opioid users.The data were compiled from volunteers who participated in clinical studies at a contract research organization in Toronto, Ontario, Canada.Data were collected from 5,018 male and female recreational opioid users via telephone and face-to-face screening interviews. Five recreational opioid users participated in a live interview broadcast on the internet.Demographic data, recreational drug use history, routes of recreational drug administration, alcohol use, and smoking status. A subset of the demographic information and recreational drug use history was summarized separately using data collected between 2013 and 2016 from 114 recreational opioid users who were not dependent on opioids. Interview excerpts were included from five recreational opioid users who described their real-world experiences with drug abuse, including the impact of abuse-deterrent opioid formulations on their drug abuse behavior.The preferred route of administration of opioids was oral (52 percent), followed by intranasal (36 percent), intravenous (10 percent), and buccal (chewing on a patch; 2 percent). Other substances used included nicotine, alcohol, and non-opioid psychoactive drugs (primarily cannabis). Oxycodone was the most frequently reported opioid of abuse.Recreational opioid users have distinct drug-related behaviors and preferences. Monitoring current trends and examining these behaviors is an important component to understand the potential safety risks associated with recreational opioid use.

The aim of this study is to shed the light on the oral cavity profile assessing teeth and periodontal tissues in previously illicit drug abusers of cannabis and heroin with different drug addiction circumstances.Study population included 100 inmates, aged 21-64 years, incarcerated for previous addiction to cannabis or heroin. Personal information and drug circumstances of addiction were registered with dental and periodontal parameters including daily teeth brushing frequency, decayed missed filled teeth (DMFT), plaque index (PI), gingival index (GI), bleeding on probing (BOP), recession, and clinical attachment loss (CAL).Half of the population were illiterate, and 70% were married. Heroin was the most previously abused drug and more than 70% of the participants had been addicted for more than 12 months. Low teeth brushing activity profile dominated with higher values for DMFT and BOP in the heroin group compared with the cannabis (after age adjustment) (DMFT = 22.6 ± 7.9, 18.5 ± 9.8, respectively, P = 0.03) (BOP = 60% ± 30%, 66.6% ± 32%, respectively). In addition, higher values of BOP were recorded in the heroin injecting group compared with both of heroin fumes inhalation and cannabis smoking (BOP = 76.41% ± 27.7%, 59.12% ± 33.6%, 60.05% ± 31.8% P = 0.04, respectively), whereas PI, GI, Reces, and CAL means were comparable among groups regardless of other addiction circumstances.Abused drug type and the way its chemical form being administered would negatively affect, directly or indirectly, the oral cavity concomitantly with the sustained state of self-negligence and less interest in implementing the oral hygiene measurements. Altogether, addiction circumstances synergize leading to a distinctive dental and oral profile which would impose a burden to adapt a more customized treatment approach.

Chemsex refers to the use of sex-enhancing drugs among men who have sex with men (MSM) in combination with specific sexual and social behaviours. Longitudinal data on this development and the associated health risks are scarce.Data on all recreational drugs reported in the Swiss HIV Cohort Study (SHCS) from 2007 to 2017 were collected. Drug use was analysed longitudinally for all drug classes. In addition, potential associations between patient characteristics and the consumption of methamphetamine, γ-hydroxybutric acid/γ-butyrolactone (GHB/GBL), 3,4-methylenedioxymethamphetamine (MDMA/XTC), cocaine and amphetamine were analysed.We analysed 166 167 follow-up entries for 12 527 SHCS participants, including 7101 free text field entries containing information about recreational drugs other than cannabis, cocaine and heroin. Overall, we observed a stable percentage (9.0%) of recreational drug use (excluding cannabis, amyl nitrite and prescription drugs). For MSM, however, there was an increase in overall drug use from 8.8% in 2007 to 13.8% in 2017, with particularly large increases for methamphetamine (from 0.2 to 2.4%; P < 0.001) and GHB/GBL (from 1.0 to 3.4%; P < 0.001). The use of each of the potentially sex-enhancing drugs methamphetamine, GHB/GBL, cocaine, XTC/MDMA and amphetamine was significantly associated with condomless sex with nonsteady partners, and higher prevalences of depression, syphilis and hepatitis C.The significant increase in the use of chemsex drugs among MSM in the SHCS and the strong association with coinfections and depression highlights the need for harm reduction programmes tailored to MSM. According to our results, improving knowledge about recreational drugs is important for all health care professionals working with people living with HIV.

Organic molecules that bind to cannabinoid receptors are called cannabinoids, and they have similar pharmacological properties like the plant, Cannabis sativa L. Hyphenated liquid chromatography (LC), incorporating high-performance liquid chromatography (HPLC) and ultra-performance liquid chromatography (UPLC, also known as ultrahigh-performance liquid chromatography, UHPLC), usually coupled to an ultraviolet (UV), UV-photodiode array (PDA) or mass spectrometry (MS) detector, has become a popular analytical tool for the analysis of naturally occurring cannabinoids in various matrices.To review literature on the use of various LC-based analytical methods for the analysis of naturally occurring cannabinoids published since 2010.A comprehensive literature search was performed utilising several databases, like Web of Knowledge, PubMed and Google Scholar, and other relevant published materials including published books. The keywords used, in various combinations, with cannabinoids being present in all combinations, in the search were Cannabis, hemp, cannabinoids, Cannabis sativa, marijuana, analysis, HPLC, UHPLC, UPLC, quantitative, qualitative and quality control.Since 2010, several LC methods for the analysis of naturally occurring cannabinoids have been reported. While simple HPLC-UV or HPLC-UV-PDA-based methods were common in cannabinoids analysis, HPLC-MS, HPLC-MS/MS, UPLC (or UHPLC)-UV-PDA, UPLC (or UHPLC)-MS and UPLC (or UHPLC)-MS/MS, were also used frequently. Applications of mathematical and computational models for optimisation of different protocols were observed, and pre-analyses included various environmentally friendly extraction protocols.LC-based analysis of naturally occurring cannabinoids has dominated the cannabinoids analysis during the last 10 years, and UPLC and UHPLC methods have been shown to be superior to conventional HPLC methods.

Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal movements and postures. Besides motor manifestations, patients with dystonia also display non-motor signs and symptoms including psychiatric and sensory disturbances. Symptomatic treatment of motor signs in dystonia largely relies on intramuscular botulinum toxin injections and, in selected cases, on deep brain stimulation. Oral medications and physical therapy offer a few benefits only in a minority of patients. Cannabinoids have been shown to be a complementary treatment in several neurological disorders but their usefulness in dystonia have not been systematically assessed. Given recent policy changes in favor of cannabis use in clinical practice and the request for alternative treatments, it is important to understand how cannabinoids may impact people with dystonia. Reviewing the evidence so far available and our own experience, cannabinoids seem to be effective in single cases but further studies are required to improve our understanding on their role as complementary treatment in dystonia.

Glioma-related epilepsy significantly impact on patients' quality of life, and can often be difficult to treat. Seizures cause significant morbidity for example neurocognitive deterioration, which may result from seizures themselves or due to adverse effects from antiepileptic drugs. Management of tumour with surgery, radiotherapy and chemotherapy may contribute to seizure control, but tumour related epilepsy is often refractory despite adequate treatment with standard anti-epileptic medications. Given the increasing interest in medicinal cannabis (or cannabidiol or CBD) as an anti-epileptic drug, CBD may help with seizure control in glioma patients with treatment-refractory seizures. Here we present a case of a young lady with recurrent glioma who had refractory seizures despite multiple anti-epileptic agents, who had significant benefit with CBD.

Cannabidiol (CBD) is a non-psychoactive cannabinoid, widely marketed to athletes for claimed effects such as decreased anxiety, fear memory extinction, anti-inflammatory properties, relief of pain and for post-exercise recovery. The World Anti-Doping Agency (WADA) has excluded CBD from its list of prohibited substances. Nevertheless, caution is currently advised for athletes intending to use the compound-except CBD, all other cannabinoids are still on the prohibited list. CBD products, specifically non-medicinal, so-called full-spectrum cannabis extracts, may contain significant levels of these substances, but also contaminations of tetrahydrocannabinol (THC) (>2.5 mg/day in >30% of products on the German market) potentially leading to positive doping tests. Labelled claims about CBD content and absence of THC are often false and misleading. Contaminations with the psychoactive THC can result in adverse effects on cognition and, in general, the safety profile of CBD with respect to its toxicity is a controversial topic of discussion. For these reasons, we would currently advise against the use of over-the-counter CBD products, especially those from dubious internet sources without quality control.

Cannabis currently leads to intensive, and sometimes highly emotional discussions like no other drug. What are the health and social risks, if the substance is used recreationally? This article describes the most important cannabinoids, the endogenous cannabinoid system and possible risks of cannabis if used as drug. Psychotherapeutic treatment options of cannabis abuse and dependence are shown.

Tobacco and marijuana co-use among young people in the U.S. is a public health concern that deserves greater attention. This study addresses a significant gap in the literature by examining the prevalence and correlates of tobacco and marijuana co-use among young people experiencing homelessness.The analytic sample consisted of 449 unaccompanied homeless youth (mean age = 22; 72% male) who had used any type of tobacco product in the past 30 days. Participants were recruited from 12 service sites and 13 street sites in Los Angeles County.Over 90% of young homeless tobacco users reported past month marijuana and tobacco co-use: 65% reported any co-administration (mixing both substances in a cigarette, joint, blunt, bong, hookah, pipe or bowl) and 27% reported only using them separately. Analysis of covariance tests found that co-administrators reported greater quantity and frequency of tobacco cigarette use, more frequent marijuana use and, in some cases, poorer functioning and more severe homelessness compared to other tobacco users (p < 0.05). Logistic regression analysis indicated that co-administration was less likely among youth who were Black (vs. white) and who perceived it as being the same or more harmful than cigarette smoking, but more likely among youth who reported greater exposure to peers who engaged in co-administration (p < 0.05).Co-administration of tobacco and marijuana is prevalent among young tobacco users experiencing homelessness. Results add to a growing literature on the prevalence and potential risks of co-administration among young people that can inform policies aimed at regulating tobacco and marijuana products.

Opioids are the primary therapy for cancer-related pain in patients receiving palliative care. More states are legalizing medical cannabis, which may provide a pain management alternative for some of these patients. This study aimed to estimate the effect of cannabis on opioid use in patients with cancer receiving palliative care.This was a retrospective cohort study of patients with cancer at an academic medical center palliative care clinic. The primary outcome was change in morphine equivalent daily dose (MEDD) from baseline to 84-day follow-up in the cannabis plus opioid group compared to that in the opioid-only group.A total of 83 patients were included: 61 in the opioid monotherapy group and 22 in the cannabis plus opioid group. An increase in MEDD from the baseline to 84 days was seen in both the opioid monotherapy and opioid plus cannabis group (28.8 vs. 10.8); however, the study lacked power to detect a statistical difference.A possibly meaningful difference in MEDD increase was seen when comparing the opioid monotherapy group with the opioid plus cannabis group. However, the study was not powered to test this hypothesis; the findings suggest that further research is warranted to determine the impact of cannabis use on opioid dosing in patients receiving palliative care for cancer.

Legalization of cannabis for recreational use has compelled governments to seek new tools to accurately monitor Δ9-tetrahydrocannabinol (Δ9-THC) and understand its effect on impairment. Various methods have been employed to measure Δ9-THC, and its respective metabolites, in different biological matrices. Recently, breath analysis has gained interest as a non-invasive method for detection of chemicals that are either produced as part of biological processes or are absorbed from the environment. Existing breath analyzers function by analyzing previously collected samples or by direct real-time analysis. Portable hand-held devices are of particular interest for law-enforcement and personal use. This paper reviews and compares both commercially available and prototype devices that proclaim Δ9-THC detection in exhaled breath using methods such as Field Asymmetric Ion Mobility Spectrometry, Semiconductor-Enriched Single-Walled Carbon Nanotube chemiresistors, Liquid Chromatography-tandem Mass-Spectrometry, microfluidic-based artificial olfaction, and optical-based gas sensing.

Cannabis is one of the most commonly sold drugs on cryptomarkets. Because of the anonymity-granting functions of Tor, no study has traced the within-country effect of the Dark Web on cannabis consumption patterns. This article uses a big data research design to examine the association between revealed interest in the Dark Web and self-reported cannabis use within US states from 2011 when Silk Road launched to 2015 when Operation Onymous shuttered nine markets.This study uses mixed effects ordinary least squared regressions to analyze U.S. state/year panel data, using robust standard errors to correct for heteroscedasticity. Marginal effect plots illustrate substantive effects. The dataset consists of state-level variables drawn from the Uniform Crime Report (UCR), the American Community Survey (ACS), the National Survey on Drug Use and Health, the Correlates of State Policy Project, and the Bureau of Justice Statistics Justice Expenditure and Employment Extracts. Data for the Dark Web interest measure are drawn from Google Trends. The proxy for Dark Web interest is an index of eight Dark Web related search queries.The regression analysis indicates that Dark Web interest in US states positively correlates with cannabis consumption rates overall and among older adults (26+), but not youth (12-17) or younger adults (18-25). Additionally, Dark Web interest is positively associated with more frequent cannabis usage rates (i.e. use in the past month, excluding first time use) both overall and among older adults, but not among youth or younger adults. Dark Web interest does not correlate with casual use (i.e. use in the last year, excluding use in the past month) for any age bracket. Interacting Dark Web interest with state-level legalization regimes indicates that the association between Dark Web interest and cannabis consumption in the past year is no different in medically legalized states and amplified in states with recreational legalization. Lastly, the Dark Web interest term does not correlate with first time cannabis either overall or for any age category.Interest in the Dark Web is associated with increased cannabis use in U.S. states from 2011-2015, but the effect is concentrated in states with more frequent cannabis users, older users, and in states with recreational legalization of cannabis.

This exploratory pilot study investigated the effects of chronic Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) on cerebral glucose metabolism in people with multiple sclerosis (PwMS). Compared to non-users, THC-users had hypermetabolism of three regions (p < 0.039, d >1.17) in left temporal areas, while CBD-users had hypometabolism of five regions (p < 0.032, d > 1.31) in left temporal areas. This study highlights the need to discriminate between THC and CBD in future cannabis studies. Novelty: • Chronic THC and CBD use had disparate effects on cerebral glucose metabolism in PwMS.

The National Guard provides critical support both domestically and abroad with soldiers dispersed throughout America and spanning the urban-rural continuum. To determine if location-specific interventions may be needed, we compared the prevalence and severity of cannabis and alcohol use among National Guard members across localities.Michigan National Guard members were enrolled (N = 2,746) during drill weekends as part of a larger randomized behavioral trial. Cannabis (ASSIST; prevalence = 5%) and alcohol use (AUDIT; prevalence = 82%) were compared using hurdle regression models across locality status after adjusting for covariates.Prevalence of cannabis and alcohol use was predicted by locality (adjusted odds ratio [AOR] = 0.913, 95% CI: 0.838-0.986, P = .029; AOR = 0.963, 95% CI: 0.929-0.998, P = .038, respectively), with more use in urban localities. Neither severity of cannabis nor alcohol use was predicted by locality status.Prevalence of cannabis and alcohol use in the National Guard is differentially elevated across localities with higher prevalence in more central, densely populated areas. Findings may inform future work considering accessibility and utilization of prevention and treatment services for Guard members across the urban-rural continuum.

This review focuses on the possible roles of phytocannabinoids, synthetic cannabinoids, endocannabinoids, and "transient receptor potential cation channel, subfamily V, member 1" (TRPV1) channel blockers in epilepsy treatment. The phytocannabinoids are compounds produced by the herb Cannabis sativa, from which Δ9-tetrahydrocannabinol (Δ9-THC) is the main active compound. The therapeutic applications of Δ9-THC are limited, whereas cannabidiol (CBD), another phytocannabinoid, induces antiepileptic effects in experimental animals and in patients with refractory epilepsies. Synthetic CB1 agonists induce mixed effects, which hamper their therapeutic applications. A more promising strategy focuses on compounds that increase the brain levels of anandamide, an endocannabinoid produced on-demand to counteract hyperexcitability. Thus, anandamide hydrolysis inhibitors might represent a future class of antiepileptic drugs. Finally, compounds that block the TRPV1 ("vanilloid") channel, a possible anandamide target in the brain, have also been investigated. In conclusion, the therapeutic use of phytocannabinoids (CBD) is already in practice, although its mechanisms of action remain unclear. Endocannabinoid and TRPV1 mechanisms warrant further basic studies to support their potential clinical applications. This article is part of the Special Issue "NEWroscience 2018".

Anxiety disorders are highly prevalent in the general population and associated with high rates of impairment and disability. This burden highlights the need to identify risk factors that individuals can modify without professional intervention. A systematic review was conducted to identify studies that examined modifiable risk and protective factors for anxiety disorders among adults in the general population. Searches were conducted in PubMed, PsycINFO and MEDLINE using medical subject headings and text words related to risk factors, protective factors, and each anxiety disorder. Screening, data extraction, and quality assessment were performed by three study authors. Modifiable risk and protective factors from 19 studies across seven countries were identified. Risk factors identified included cigarette smoking, alcohol use, cannabis use, negative appraisals of life events, avoidance, and occupational factors. Protective factors included social support, coping, and physical activity. Cigarette smoking was the most studied risk factor. Support was found for cigarette smoking as a risk factor for agoraphobia and panic disorder. Mixed results were found for generalized anxiety disorder and specific phobia. Across disorders, smoking frequency was associated with greater risk. Results indicate an important gap in the literature in that few studies have examined modifiable risk factors for anxiety disorders.

Worldwide, cannabis is the most used illegal substance, and the use of cannabis has increased over the years. An increase in the level of tetrahydrocannabinol (THC) in cannabis has also been seen. It is currently unclear whether this has led to an increase in the incidence of cannabis-induced psychosis. We aimed to investigate (1) the development of incidence of cannabis-induced psychosis over time compared with other substance-induced psychoses and (2) the development of incident cases of cannabis-induced psychosis over time compared with dual diagnosis defined as schizophrenia and a cannabis use disorder.Data on psychiatric diagnoses were extracted from the Danish Psychiatric Central Research Register and summarized per year as both absolute incidence (number of cases) and incidence rates per 100 000 person years.The incidence rate of cannabis-induced psychosis increased steadily from 2.8 per 100 000 person years in 2006 to 6.1 per 100 000 person years in 2016. There was a corresponding increase in dual diagnosis with schizophrenia and cannabis use disorder, but a decrease in alcohol-induced psychosis. The data showed no trend in the other substance-induced psychosis investigated in this thesis.The increase in cannabis-induced psychosis follows both the increase in the level of THC in cannabis, and the increase in cannabis use. The change in diagnostic practice does not appear to explain the increase in incidence of cannabis-induced psychosis.

The objectives of this study were: (1) to assess the prevalence of substance use among homeless women; (2) to examine the correlates for drug abuse; (3) to analyze paths between early stressful life events, drug abuse and mental health. The methodology was a longitudinal study of women homeless in Madrid (Spain), who were followed for a 24 months period. There were 138 participants interviewed at baseline and 73 participants interviewed at follow-up. We ran bivariate and multivariate analysis to examine the correlates for drug abuse. We also performed path analysis to test the interconnections between stressful life events, drug abuse and mental health. Results at baseline showed that 83.3% of participants had consumed at least one substance in the previous month. Tobacco was the most common substance consumed (70.1%), followed by sedatives (48.6%), alcohol (36.2%), methadone (13.7%), cocaine (7.2%), cannabis (6.5%) and heroin (5.1%). In addition, women who met criteria for drug abuse (19.6% of the sample) were more likely to be younger, have suffered adverse experiences during childhood, have engaged in prostitution, and have ever attempted suicide, in comparison with women who did not meet criteria for drug abuse. Path analysis supported that early stressful life events increased the vulnerability for subsequent negative outcomes among homeless women. These findings have significant implications for understanding how to implement programs for homeless women in Spain.

The medical use of cannabis has been legislatively restricted for decades in the US and abroad. In recent years, changing local and national policies have given rise to a community of healthcare providers who may be recommending the medical use of cannabis without the benefit of formal clinical practice guidelines or sufficient training and education. In addition, a citizen science movement has emerged whereby unlicensed and untrained individuals are acting as healthcare provider proxies, offering cannabis-specific clinical care to "patients". This study sought to characterize the clinical practice characteristics of these provider groups.An anonymous, online survey was designed to describe levels of cannabis-specific education, practice characteristics, indications for medical use, dose, administration forms and adverse effects related to cannabis use. The questionnaire was disseminated via professional medical cannabis associations and by word-of-mouth. It was accessed between June 31-December 31, 2018. A self-selecting sample of respondents (n = 171) completed the survey.Formal education or training in the medical use of cannabis was significantly more common among licensed respondents than unlicensed respondents (95.5% vs 76.9% respectively, OR, 6.3, 95% CI, 1.2-32.3, p = 0.03). The vast majority (n = 74, 83.15%) of licensed respondents reported having recommended cannabis as an adjunct to an existing prescription drug. Almost two-thirds (n = 64, 71.9%) reported having recommended it as a substitute. When delta-9-tetrahydrocannabinol (THC) is the principal therapeutic constituent of interest, vaporization is the most common method of administration recommended (n = 94 responses, 71.4% of respondents). In contrast, when cannabidiol (CBD) is the principal therapeutic constituent of interest, oral administration (sublingual or oromucosal absorption) is the most common method (n = 70 responses, 71.4% of respondents).Individuals who recommend the medical use of cannabis appear to be self-generating a community standard of practice in the absence of formal clinical guidelines on dosing, interactions and other characteristics. Reducing barriers to clinical research on cannabis products is needed, not only to better understand their risks and benefits, but also to augment the evidence-base for informing clinical practice.

Heroin (diamorphine) is a highly addictive opioid drug synthesized from morphine. The use of heroin and incidence of heroin associated overdose death has increased sharply in the US. Heroin is primarily metabolized via deacetylation (hydrolysis) forming the active metabolites 6-monoacetylmorphine (6-MAM) and morphine. A diminution in heroin hydrolysis is likely to cause higher drug effects and toxicities. In this study, we sought to determine the contribution of the major hepatic hydrolase carboxylesterase 1 (CES1) to heroin metabolism in the liver as well as the potential influence of one of its known genetic variants, G143E (rs71647871). Furthermore, given the potential therapeutic application of cannabidiol (CBD) for heroin addiction and the frequent co-abuse of cannabis and heroin, we also assessed the effects of CBD on heroin metabolism. In vitro systems containing human liver, wild-type CES1, and G143E CES1 S9 fractions were utilized in the assessment. The contribution of CES1 to the hydrolysis of heroin to 6-MAM was determined as 3.66%, and CES1 was unable to further catalyze 6-MAM under our assay conditions. The G143E variant showed a 3.2-fold lower intrinsic clearance of heroin as compared to the WT. CBD inhibited heroin and 6-MAM hydrolysis in a reversible manner, with IC50s of 14.7 and 12.1 μM, respectively. Our study results suggested only minor involvement of CES1 in heroin hydrolysis in the liver. Therefore, the G143E variant is unlikely to cause significant impact despite a much lower hydrolytic activity. CBD exhibited potent in vitro inhibition toward both heroin and 6-MAM hydrolysis, which may be of potential clinical relevance.

Background: Drug abuse in university students is an emerging social and health issue. The present study assesses alcohol and abuse of other illicit drugs and the adverse consequences related to such use and its relationship with self-care agency among European university students. Methods: A multicenter cross-sectional study was performed among 592 European students from different health science degrees. The screening of alcohol abuse was evaluated with the Alcohol Use Disorder Test (AUDIT), and the screening for substance-related risks and problems was conducted with the Car, Relax, Alone, Forget, Friends, Trouble (CRAFFT) screening test. We analyzed the relationship of substance abuse with self-care agency, assessed by the Appraisal of Self-Care Agency Scale (ASA). Results: 51.4% of the surveyed students reported alcohol intake, 16.6% of the students consumed both alcohol and cannabis, 1.6 % reported alcohol and other illicit drugs, and 3.7% consumed alcohol, marijuana, and other illicit drugs (73.3% of students reported alcohol intake alone or together with cannabis/hashish and/or other illicit drugs). The self-care agency scores were significantly different among groups in relation to certain sociodemographic factors such as gender (p = 0.008) and country of residence (p = 0.031). The self-care agency scores significantly correlated (p = 0.001) with the personal motivations and consequences related to the consumption of drugs of abuse evaluated by the CRAFFT screening tool. Within the ASA domains, the most significant effects were observed regarding the subdomains of resources, awareness, and health behaviors. Conclusions: Self-care agency should be promoted to counteract the health and social consequences of the consumption of drugs of abuse among university students who will be future health care professionals.

This Doolin Memorial Lecture presents six suggestions for positive change in Ireland's mental health services, focused on legislation and rights: (a) revision of the Mental Health Act 2001 in line with existing recommendations, to better protect and promote a broad range of rights, including rights to treatment and liberty (which are related); (b) enhanced forensic mental health care to better protect and promote both treatment and liberty in this population; (c) prompt full implementation of the Public Health (Alcohol) Act 2018 to reduce alcohol-related harm and the opportunity cost of alcohol problems in the health service; (d) implementation of the Assisted Decision-Making (Capacity) Act 2015 to provide decision-making supports to the 29.4% of medical/surgical inpatients and 52.6% of psychiatry inpatients who lack full decision-making capacity for treatment decisions; (e) judicious medicalisation of our response to individual cannabis use (although legalisation is not advised); and (f) enhanced recognition of the social rights of the mentally ill, especially the right to housing. Attention to these areas would improve the quality of life and quality of liberty of people with mental illness and their families. Progress in these areas needs to be underpinned by enhanced involvement of service-users in planning and provision of care, increased funding of mental health services and particular attention to groups who are currently underserved, including children and adolescents. Enhanced attention to these areas would also help advance Ireland's national mental health policy, "A Vision for Change", which has yet to be implemented in full. That, too, would help.

Early adolescence (10-16 years) is a crucial period for physical, mental and cognitive development where a wide range of school, behaviour and health-related difficulties may occur. These issues may be aggravated in adolescents with early affective/sexual live and contraceptive consultation. This study assessed the risk of school, behaviour and health-related problems among younger boys and girls having a contraceptive consultation. Such knowledge would inform care providers about their main role in monitoring and caring adolescent problems.This cross-sectional study included 1559 middle-school adolescents from north- eastern France (mean age 13.5+1.3). They completed a questionnaire gathering socioeconomic features, obesity, school difficulties, substances use, physical health, psychological health, social relationship, violence, sexual abuse, and suicide behaviours. Data were analysed for each gender separately using logistic regression models.The contraceptive consultation concerned 6.7% of girls and 3.2% of boys (P=0.002). Based on odds ratio (adjusted for age, school-class level and socioeconomic factors), both boys and girls with contraceptive consultation had 2-to-7-time higher risk of consumption of alcohol, tobacco, cannabis and other drogues, poor physical health, relational problems, and perpetrated violence. Additionally, the girls had a 4-time higher risk of low academic-performance and being obese while the boys had 6-to-37-time higher risk of sexual abuse, school dropout ideation, suicide ideation and suicide attempts.Although based on self-reported data, we found that primary care providers play a prominent role in detecting and monitoring school, behaviour and health-related problems during adolescent contraceptive consultations.

The use of cannabis has previously been linked to both depression and self-harm; however, the role of genetics in this relationship is unclear. This study aimed to estimate the phenotypic and genetic associations between cannabis use and depression and self-harm.Cross-sectional data collected through UK Biobank were used to test the phenotypic association between cannabis use, depression and self-harm. UK Biobank genetic data were then combined with consortia genome-wide association study summary statistics to further test the genetic relationships between these traits using LD score regression, polygenic risk scoring and Mendelian randomization methods.United Kingdom, with additional international consortia data.A total of 126 291 British adults aged between 40 and 70 years, recruited into UK Biobank.Phenotypic outcomes were life-time history of cannabis use (including initial and continued cannabis use), depression (including single-episode and recurrent depression) and self-harm. Genome-wide genetic data were used and assessment centre, batch and the first six principal components were included as key covariates when handling genetic data.In UK Biobank, cannabis use is associated with an increased likelihood of depression [odds ratio (OR) = 1.64, 95% confidence interval (CI) = 1.59-1.70] and self-harm (OR = 2.85, 95% CI = 2.69-3.01). The strength of this phenotypic association is stronger when more severe trait definitions of cannabis use and depression are considered. Using consortia genome-wide summary statistics, significant genetic correlations are seen between cannabis use and depression [rg = 0.289, standard error (SE) = 0.036]. Polygenic risk scores for cannabis use and depression explain a small but significant proportion of variance in cannabis use, depression and self-harm within a UK Biobank target sample. However, two-sample Mendelian randomization analyses were not significant.Cannabis use appeared to be both phenotypically and genetically associated with depression and self-harm. Limitations in statistical power mean that conclusions could not be made on the direction of causality between these traits.

Young adult college students in the United States are likely to be affected by marijuana liberalization trends. However, changes in students' marijuana use following recreational marijuana legalization (RML) have not been examined in more than one RML state at a time, or beyond 1-2 years post-legalization.Cross-sectional National College Health Assessment survey administered twice yearly from 2008 to 2018.A total of 587 4-year colleges and universities in 48 US states.Undergraduates aged 18-26 years attending college in US states that did (n = 234 669 in seven states) or did not (n = 599 605 in 41 states) enact RML between 2008 and 2018.Self-reported marijuana use (past 30 days) and individual and contextual covariates, institution-provided institutional and community covariates and publicly available dates when states enacted RML.Adjusting for covariates, state differences and state-specific linear time trends (accounting for pre-RML trends), prevalence of 30-day marijuana use increased more among students exposed to RML [odds ratio (OR) = 1.23, 95% confidence interval (CI) = 1.19-1.28, P < 0.001] than among non-RML state students throughout the same time-period; the results were similar for frequent use (≥ 20 days) (OR = 1.18, 95% CI = 1.10-1.27, P < 0.001). Interaction models supported stronger RML effects among students who were female, residing off-campus and aged 21 years and older; sexual orientation did not moderate RML effects. In the earliest states to enact RML (2012) there were increases in use prevalence in the second through the sixth year post-RML compared to pre-RML. In the second legalization group (2015) there were increases in the first and second year post-RML, and greater increases in the third year. In the later states (2016-17), increases were observed in both years after RML.In US states that enacted recreational marijuana legislation from 2012 to 2017 there was evidence for a general trend towards greater increases in marijuana use by college students and differential impact by gender, legal using age and campus residence.

Pain is a common and complex symptom of cancer having physical, social, spiritual and psychological aspects. Approximately 70%-80% of cancer patients experiences pain, as reported in India. Ayurveda recommends use of Shodhita (Processed) Bhanga (Cannabis) for the management of pain but no research yet carried out on its clinical effectiveness.To assess the analgesic potential of Jala-Prakshalana (Water-wash) processed Cannabis sativa L. leaves powder in cancer patients with deprived quality of life (QOL) through openlabel single arm clinical trial.Waterwash processed Cannabis leaves powder filled in capsule, was administered in 24 cancer patients with deprived QOL presenting complaints of pain, anxiety or depression; for a period of 4 weeks; in a dose of 250 mg thrice a day; along with 50 ml of cow's milk and 4 g of crystal sugar. Primary outcome i.e. pain was measured by Wong-Bakers FACES Pain Scale (FACES), Objective Pain Assessment (OPA) scale and Neuropathic Pain Scale (NPS). Secondary outcome namely anxiety was quantified by Hospital Anxiety and Depression Scale (HADS), QOL by FACT-G scale, performance score by Eastern Cooperative Oncology Group (ECOG) and Karnofsky score.Significant reduction in pain was found on FACES Pain Scale (P < 0.05), OPA (P < 0.05), NPS (P < 0.001), HADS (P < 0.001), FACT-G scale (P < 0.001), performance status score like ECOG (P < 0.05) and Karnofsky score (P < 0.01).Jalaprakshalana Shodhita Bhanga powder in a dose of 250 mg thrice per day; relieves cancerinduced pain, anxiety and depression significantly and does not cause any major adverse effect and withdrawal symptoms during trial period.

Anecdotal evidence that cannabis preparations have medical benefits together with the discovery of the psychotropic plant cannabinoid Δ9-tetrahydrocannabinol (THC) initiated efforts to develop cannabinoid-based therapeutics. These efforts have been marked by disappointment, especially in relation to the unwanted central effects that result from activation of cannabinoid receptor 1 (CB1), which have limited the therapeutic use of drugs that activate or inactivate this receptor. The discovery of CB2 and of endogenous cannabinoid receptor ligands (endocannabinoids) raised new possibilities for safe targeting of this endocannabinoid system. However, clinical success has been limited, complicated by the discovery of an expanded endocannabinoid system - known as the endocannabinoidome - that includes several mediators that are biochemically related to the endocannabinoids, and their receptors and metabolic enzymes. The approvals of nabiximols, a mixture of THC and the non-psychotropic cannabinoid cannabidiol, for the treatment of spasticity and neuropathic pain in multiple sclerosis, and of purified botanical cannabidiol for the treatment of otherwise untreatable forms of paediatric epilepsy, have brought the therapeutic use of cannabinoids and endocannabinoids in neurological diseases into the limelight. In this Review, we provide an overview of the endocannabinoid system and the endocannabinoidome before discussing their involvement in and clinical relevance to a variety of neurological disorders, including Parkinson disease, Alzheimer disease, Huntington disease, multiple sclerosis, amyotrophic lateral sclerosis, traumatic brain injury, stroke, epilepsy and glioblastoma.

The impact of medical cannabis on healthcare utilisation between 2014 and 2017 in Ontario, Canada. With cannabis legalisation in Canada and some states in the USA, high-quality longitudinal cohort research studies are of urgent need to assess the impact of cannabis use on healthcare utilisation.A matched cohort study of 9925 medical cannabis authorised adult patients (inhaled (smoked or vaporised) or orally consumed (oils)) at specialised cannabis clinics, and inclusion of 17 732 controls (not authorised) between 24 April 2014 and 31 March 2017 from Ontario, Canada. Interrupted time series and multivariate Poisson regression analyses were conducted. Medical cannabis impact on healthcare utilisation was measured over 6 months: all-cause physician visits, all-cause hospitalisation, ambulatory care sensitive conditions (ACSC)-related hospitalisations, all-cause emergency department (ED) visits and ACSC-related ED visits.For medical cannabis patients compared with controls, there was an initial (within the first month) increase in physician visits (additional 4330 visits per 10 000 patients). However, a numerical reduction was noted over the 6-month follow-up, and no statistical difference was observed (p=0.126). Likewise, in hospitalisations and ACSC ED visits, there was an initial increase (44 per 10 000 people, p<0.05) but no statistical difference after follow-up (p=0.34). Conversely, no initial increase in all-cause ED visits was observed with a slight decrease (19 visits per 10 000 patients, p=0.014) in follow-up.An initial increase (within first month) in healthcare utilisation may be expected among medical cannabis users that appears to wane over time. Proactive follow-up of patients using medical cannabis is warranted to minimise initial risks to patients and actively assess potential benefits/harms of ongoing use.

Annual '4/20' cannabis festivals occur around the world on April 20 and often feature synchronised consumption of cannabis at 4:20 pm. The relationship between these events and demand for emergency medical services has not been systematically studied.We conducted a population-based retrospective cohort study in Vancouver, Canada, using 10 consecutive years of data (2009-2018) from six regional hospitals. The number of emergency department (ED) visits between 4:20 pm and 11:59 pm on April 20 were compared with the number of visits during identical time intervals on control days 1 week earlier and 1 week later (ie, April 13 and April 27) using negative binomial regression.A total of 3468 ED visits occurred on April 20 and 6524 ED visits occurred on control days. A non-significant increase in all-cause ED visits was observed on April 20 (adjusted relative risk: 1.06; 95% CI 1.00 to 1.12). April 20 was associated with a significant increase in ED visits among prespecified subgroups including a 5-fold increase in visits for substance misuse and a 10-fold increase in visits for intoxication. The hospital closest to the festival site experienced a clinically and statistically significant 17% (95% CI 5.1% to 29.6%) relative increase in ED visits on April 20 compared with control days.Substance use at annual '4/20' festivals may be associated with an increase in ED visits among key subgroups and at nearby hospitals. These findings may inform harm reduction initiatives and festival medical care service planning.

This study explored the attitudes of the Arkansas community toward medical cannabis (MC) regulation and the role of pharmacists in dispensing MC before the product became available and examined whether participants' demographics (e.g., age, gender) and characteristics (e.g., history of cannabis use) were associated with these attitudes.Cross-sectional survey.Using social media, a university research registry, and posted flyers, we invited residents of Arkansas to participate in the self-administered online survey study during a 3-month period, February to April, in 2018.Five questions that inquired about participants' attitudes toward MC regulation and pharmacists' roles regarding MC use.Participants (n = 1343) who completed at least 1 of the 5 questions were included. The majority were aged 40-64 years (52.2%), female (69.1%), and white (88.7%). Most participants reported a history of cannabis use (81.8%) and possession or intention to apply for an MC card (52.9%). Among the conditions approved for MC use, pain (20.3%), arthritis (15.4%), and posttraumatic stress disorder (14.5%) were reported frequently. Likewise, prescription use for mood disorders (46.1%) and pain (37.4%) were also reported. In multivariable regression analyses, participants' history of cannabis use was associated with a preference for lesser oversight of MC, disagreement with MC being available through a pharmacy only, and disagreement on whether MC should be regulated before it is legalized for recreational use (all P < 0.001). It was also associated with a decrease in agreement that pharmacists are well-trained to improve patient safety (P < 0.001) and counsel patients regarding appropriate MC use (P = 0.032).Participants who had previously used cannabis were in favor of fewer restrictions and negatively perceived pharmacists' involvement in ensuring appropriate dispensing and MC use. The findings may highlight the need for Arkansas pharmacists to explore alternative ways to promote the safe and proper MC use.

In drug development, the creation of highly selective ligands has been unsuccessful for the treatment of central nervous system disorders. Multi-target ligands, from the polypharmacology paradigm, are being proposed as treatments for these complex disorders, since they offer enhanced efficacy and a strong safety profile. Natural products are the best examples of multi-target compounds, so they are of high interest within this paradigm. Additionally, recent research on psychoactive drugs of natural origin, such as ayahuasca and cannabis, has demonstrated promising therapeutic potential for the treatment of some psychiatric and neurological disorders. In this text, we describe how research on psychoactive drugs can be effectively combined with the polypharmacology paradigm, providing ayahuasca and cannabis research as examples. The advantages and disadvantages are also discussed.

Introduction: In 2016, a new addiction treatment service was established in Greenland to tackle the addiction problems with alcohol, cannabis and gambling among the population. The new service has established a treatment center in each of the five municipalities and works in partnership with a central private provider of treatment for those who reside in areas without a local treatment center.Methods: The national addiction database provided us with data from the Alcohol Use Disorder Identification Test, Alcohol Severity Index and questions on cannabis use and gambling behavior received at referral to, and at initiation of treatment. The data were analyzed for differences between the population in local or central treatment using SPSS version 25 (SPSS Inc., Chicago, IL).Results: Significant differences between the individuals in local and central treatment were revealed. Individuals in local treatment are more often women with minor children and a job, and their alcohol use is concentrated on weekends/holidays. Individuals in central treatment are more equal in both genders, few have minor children living at home, heavy drinking is more pronounced, and cannabis is used more frequently as well.Discussion: The findings support our expectations of local treatment being more attractive to individuals with obligations at home. The differences in the populations are worth considering when planning the treatment service, as the needs of the populations might differ. The findings are limited by many missing in the analyses, which we believe is caused by the establishing process of the new service.

We examined whether exercising indoors vs. outdoors reduced the cardio-respiratory effects of outdoor air pollution. Adults ≥55 were randomly assigned to exercise indoors when the Air Quality Health Index was ≥5 and outdoors on other days (intervention group, n = 37), or outdoors everyday (control group, n = 35). Both groups completed cardio-respiratory measurements before and after exercise for up to 10 weeks. Data were analyzed using linear mixed effect regression models. In the control group, an interquartile range increase in fine particulate matter (PM2.5) was associated with increases of 1.4% in heart rate (standard error (SE) = 0.7%) and 5.6% (SE = 2.6%) in malondialdehyde, and decreases of 5.6% (SE = 2.5%) to 16.5% (SE = 7.5%) in heart rate variability measures. While the hypothesized benefit of indoor vs. outdoor exercise could not be demonstrated due to an insufficient number of intervention days (n = 2), the study provides evidence of short-term effects of air pollution in older adults. ISRCTN #26552763.

Even low levels of substance misuse by people with a severe mental illness can have detrimental effects.To assess the effects of psychosocial interventions for reduction in substance use in people with a serious mental illness compared with standard care.The Information Specialist of the Cochrane Schizophrenia Group (CSG) searched the CSG Trials Register (2 May 2018), which is based on regular searches of major medical and scientific databases.We included all randomised controlled trials (RCTs) comparing psychosocial interventions for substance misuse with standard care in people with serious mental illness.Review authors independently selected studies, extracted data and appraised study quality. For binary outcomes, we calculated standard estimates of risk ratio (RR) and their 95% confidence intervals (CIs) on an intention-to-treat basis. For continuous outcomes, we calculated the mean difference (MD) between groups. Where meta-analyses were possible, we pooled data using a random-effects model. Using the GRADE approach, we identified seven patient-centred outcomes and assessed the quality of evidence for these within each comparison.Our review now includes 41 trials with a total of 4024 participants. We have identified nine comparisons within the included trials and present a summary of our main findings for seven of these below. We were unable to summarise many findings due to skewed data or because trials did not measure the outcome of interest. In general, evidence was rated as low- or very-low quality due to high or unclear risks of bias because of poor trial methods, or inadequately reported methods, and imprecision due to small sample sizes, low event rates and wide confidence intervals. 1. Integrated models of care versus standard care (36 months) No clear differences were found between treatment groups for loss to treatment (RR 1.09, 95% CI 0.82 to 1.45; participants = 603; studies = 3; low-quality evidence), death (RR 1.18, 95% CI 0.39 to 3.57; participants = 421; studies = 2; low-quality evidence), alcohol use (RR 1.15, 95% CI 0.84 to 1.56; participants = 143; studies = 1; low-quality evidence), substance use (drug) (RR 0.89, 95% CI 0.63 to 1.25; participants = 85; studies = 1; low-quality evidence), global assessment of functioning (GAF) scores (MD 0.40, 95% CI -2.47 to 3.27; participants = 170; studies = 1; low-quality evidence), or general life satisfaction (QOLI) scores (MD 0.10, 95% CI -0.18 to 0.38; participants = 373; studies = 2; moderate-quality evidence). 2. Non-integrated models of care versus standard care There was no clear difference between treatment groups for numbers lost to treatment at 12 months (RR 1.21, 95% CI 0.73 to 1.99; participants = 134; studies = 3; very low-quality evidence). 3. Cognitive behavioural therapy (CBT) versus standard care There was no clear difference between treatment groups for numbers lost to treatment at three months (RR 1.12, 95% CI 0.44 to 2.86; participants = 152; studies = 2; low-quality evidence), cannabis use at six months (RR 1.30, 95% CI 0.79 to 2.15; participants = 47; studies = 1; very low-quality evidence) or mental state insight (IS) scores by three months (MD 0.52, 95% CI -0.78 to 1.82; participants = 105; studies = 1; low-quality evidence). 4. Contingency management versus standard care We found no clear differences between treatment groups for numbers lost to treatment at three months (RR 1.55, 95% CI 1.13 to 2.11; participants = 255; studies = 2; moderate-quality evidence), number of stimulant positive urine tests at six months (RR 0.83, 95% CI 0.65 to 1.06; participants = 176; studies = 1) or hospitalisations (RR 0.21, 95% CI 0.05 to 0.93; participants = 176; studies = 1); both low-quality evidence. 5. Motivational interviewing (MI) versus standard care We found no clear differences between treatment groups for numbers lost to treatment at six months (RR 1.71, 95% CI 0.63 to 4.64; participants = 62; studies = 1). A clear difference, favouring MI, was observed for abstaining from alcohol (RR 0.36, 95% CI 0.17 to 0.75; participants = 28; studies = 1) but not other substances (MD -0.07, 95% CI -0.56 to 0.42; participants = 89; studies = 1), and no differences were observed in mental state general severity (SCL-90-R) scores (MD -0.19, 95% CI -0.59 to 0.21; participants = 30; studies = 1). All very low-quality evidence. 6. Skills training versus standard care At 12 months, there were no clear differences between treatment groups for numbers lost to treatment (RR 1.42, 95% CI 0.20 to 10.10; participants = 122; studies = 3) or death (RR 0.15, 95% CI 0.02 to 1.42; participants = 121; studies = 1). Very low-quality, and low-quality evidence, respectively. 7. CBT + MI versus standard care At 12 months, there was no clear difference between treatment groups for numbers lost to treatment (RR 0.99, 95% CI 0.62 to 1.59; participants = 327; studies = 1; low-quality evidence), number of deaths (RR 0.60, 95% CI 0.20 to 1.76; participants = 603; studies = 4; low-quality evidence), relapse (RR 0.50, 95% CI 0.24 to 1.04; participants = 36; studies = 1; very low-quality evidence), or GAF scores (MD 1.24, 95% CI -1.86 to 4.34; participants = 445; studies = 4; very low-quality evidence). There was also no clear difference in reduction of drug use by six months (MD 0.19, 95% CI -0.22 to 0.60; participants = 119; studies = 1; low-quality evidence).We included 41 RCTs but were unable to use much data for analyses. There is currently no high-quality evidence to support any one psychosocial treatment over standard care for important outcomes such as remaining in treatment, reduction in substance use or improving mental or global state in people with serious mental illnesses and substance misuse. Furthermore, methodological difficulties exist which hinder pooling and interpreting results. Further high-quality trials are required which address these concerns and improve the evidence in this important area.

Cannabis proofed to be effective in pain relief, but one major side effect is its influence on memory in humans. Therefore, the role of memory on central processing of nociceptive information was investigated in healthy volunteers.In a placebo-controlled cross-over study including 22 healthy subjects, the effect of 20 mg oral Δ9-tetrahydrocannabinol (THC) on memory involving nociceptive sensations was studied, using a delayed stimulus discrimination task (DSDT). To control for nociceptive specificity, a similar DSDT-based study was performed in a subgroup of thirteen subjects, using visual stimuli.For each nociceptive stimulus pair, the second stimulus was associated with stronger and more extended brain activations than the first stimulus. These differences disappeared after THC administration. The THC effects were mainly located in two clusters comprising the insula and inferior frontal cortex in the right hemisphere, and the caudate nucleus and putamen bilaterally. These cerebral effects were accompanied in the DSDT by a significant reduction of correct ratings from 41.61% to 37.05% after THC administration (rm-ANOVA interaction "drug" by "measurement": F (1,21) = 4.685, p = 0.042). Rating performance was also reduced for the visual DSDT (69.87% to 54.35%; rm-ANOVA interaction of "drug" by "measurement": F (1,12) = 13.478, p = 0.003) and reflected in a reduction of stimulus-related brain deactivations in the bilateral angular gyrus.Results suggest that part of the effect of THC on pain may be related to memory effects. THC reduced the performance in DSDT of nociceptive and visual stimuli, which was accompanied by significant effects on brain activations. However, a pain specificity of these effects cannot be deduced from the data presented.

Electronic vapor products (EVPs), including e-cigarettes, can be used to aerosolize many substances. Examination of substances used in EVPs by US adults has been limited; we assessed past-year use of EVPs to deliver various substances.Data came from the 2017 SummerStyles Survey, a web-based survey of US adults (N = 4107). Ever EVP users were asked if they had used nicotine, marijuana, flavors or "something else" in an EVP during the past year. Weighted estimates for any, exclusive, and combined EVP substance use were calculated among ever (n = 586) and current (past 30-day; n = 121) EVP users.Past-year use of nicotine, flavors, and marijuana in EVPs was 30.7%, 23.6%, and 12.5% among ever EVP users, respectively; and 72.3%, 54.6%, and 17.8% among current EVP users. Among ever EVP users, the most commonly used substances were nicotine only (29.6%), nicotine plus flavors (27.2%), flavors only (16.4%), and marijuana only (14.9%). Among current EVP users, the most common substances used were nicotine plus flavors (39.1%), nicotine only (29.6%), and flavors only (11.2%). Among ever users, males and 18-29 year olds were more likely to report use of flavors than females and respondents ≥30 years.Approximately 7 in 10 current EVP users reported nicotine use, about 1 in 2 used flavors, and nearly 1 in 6 used marijuana. These findings suggest that EVPs are used to consume a variety of substances and could guide efforts to address tobacco and non-tobacco substance use.

Despite compelling evidence that cannabis use is associated with neurocognitive deficits, loss of cerebral gray matter, relapse and rehospitalization, a substantial number of individuals with early psychosis continue to use recreational or medicinal marijuana. One identified pathway to relapse is non-adherence. Recurrent relapses modify the trajectory of illness and culminate in long-term disability. Long-acting antipsychotic medications are superior to oral equivalents in preventing relapse.The current paper sought to examine the role of long-acting antipsychotics in preventing relapse in cannabis using early psychosis patients.The present retrospective study, which was based in an early psychosis program in mid-Michigan, examined the association between patient perceptions of antipsychotic medication and subsequent rehospitalization, among cannabis users (n = 24) and non-users (n = 27). Patient perceptions of antipsychotic medications were assessed using a single question from the NAVIGATE Patient Self-Rating Form: "Between now and your next visit, do you think we should keep your medication the same, or consider changing the medication?".Cannabis users were substantially more likely to report dissatisfaction with antipsychotic medication (Pearson Chi-square 9.67, df = 1.0, p < 0.002), and more likely to experience rehospitalization (Pearson Chi-square 4.40, df = 1.0, p = 0.036). Those maintained on long-acting injectable antipsychotic medications were rehospitalized less frequently when compared to others maintained on oral formulations (Pearson Chi-square 4.61, df = 1.0, p = 0.032).Dissatisfaction with antipsychotics may predict non-adherence and subsequent rehospitalization in early psychosis patients who use cannabis. Long-acting antipsychotics may prevent rehospitalization.

The increasing availability of cannabis for both recreational and medicinal purposes means that anaesthetists will encounter an increasing number of patients taking cannabis-based medications. The existing evidence base is conflicted and incomplete regarding the indications, interactions and long-term effects of these substances. Globally, most doctors have had little education regarding the pharmacology of cannabis-based medicines, despite the endocannabinoid system being one of the most widespread in the human body. Much is unknown, and much is to be decided, including clarifying definitions and nomenclature, and therapeutic indications and dosing. Anaesthetists, Intensivists, Pain and Perioperative physicians will want to contribute to this evidence base and attempt to harness such therapeutic benefits in terms of pain relief and opiate-avoidance, anti-emesis and seizure control. We present a summary of the pharmacology of cannabis-based medicines including anaesthetic interactions and implications, to assist colleagues encountering these medicines in clinical practice.

In Canada, federal regulations allow Nurse Practitioners (NPs) to authorize medical cannabis. Nursing regulatory bodies, however, have been hesitant to include medical cannabis within NPs' scope of practice. As the interest in cannabis increases, NPs have the potential to play a pivotal role in promoting the safe and appropriate use of cannabis. This study aimed to: summarize nursing policies in Canada related to medical cannabis; explore the perspective of nursing regulatory bodies regarding practice and policy issues related to medical cannabis; and examine the inclusion of medical cannabis content within Canadian NP curricula.A descriptive study was conducted that comprised three phases. The first phase reviewed nursing regulatory bodies' existing policies related to medical cannabis. In the second phase, practice consultants from nursing regulatory bodies were interviewed regarding policies and practices issues related to medical cannabis. The interviews were analyzed using thematic analysis. The third phase was a national survey of NP program coordinators regarding inclusion of cannabis in curricula. Descriptive statistics summarized survey responses.Of the 12 nursing regulatory bodies in Canada, only 7 had policies or statements related to cannabis, with only Ontario allowing NPs to authorize medical cannabis. There was confusion among practice consultants regarding the role of nurses in the administration of medical cannabis and several barriers were identified regarding nursing engagement in care related to medical cannabis, including lack of knowledge and clinical guidelines. 60% of NP programs included cannabis in their curricula, however, less than half addressed the risks and benefits of medical cannabis and dosing and administration protocols. Limited faculty expertise was a barrier to including cannabis content in NP curricula.Nursing regulatory bodies must be proactive in developing policies and educational resources that will support nurses in providing safe and informed care related to cannabis. To ensure patients using medical cannabis receive consistent and safe care from nurses, harmonized regulations and policies are needed across all jurisdictions. Education programs must also provide updated knowledge and training for both registered nurses and NPs that will support them in providing non-judgemental and evidence-based care to the growing number of individuals using cannabis.

The increasing medicinal use of cannabis during recent years has largely overlooked children and pregnant women due to litigious and ethical concerns. However, over the last few years medicine has observed increasing numbers of children treated with cannabis for autism spectrum disorder (ASD) and fetal alcohol spectrum disorder (FASD), and pregnant women treated for hyperemesis gravidarum (HG). This review provides an account of major findings discovered through this research. Specifically, cannabis may offer therapeutic advantages to behavioral symptoms of autism spectrum disorder and fetal alcohol spectrum disorder, and to the severe nausea and vomiting in hyperemesis gravidarum. The use of medical cannabis in children and pregnant women should be further discussed and researched in this patient population.

Adverse pharmacokinetic interactions between illicit substances and clinical drugs are of a significant health concern. Illicit substances are taken by healthy individuals as well as by patients with medical conditions such as mental illnesses, acquired immunodeficiency syndrome, diabetes mellitus and cancer. Many individuals that use illicit substances simultaneously take clinical drugs meant for targeted treatment. This concomitant usage can lead to life-threatening pharmacokinetic interactions between illicit substances and clinical drugs. Optimal levels and activity of drug-metabolizing enzymes and drug-transporters are crucial for metabolism and disposition of illicit substances as well as clinical drugs. However, both illicit substances and clinical drugs can induce changes in the expression and/or activity of drug-metabolizing enzymes and drug-transporters. Consequently, with concomitant usage, illicit substances can adversely influence the therapeutic outcome of coadministered clinical drugs. Likewise, clinical drugs can adversely affect the response of coadministered illicit substances. While the interactions between illicit substances and clinical drugs pose a tremendous health and financial burden, they lack a similar level of attention as drug-drug, food-drug, supplement-drug, herb-drug, disease-drug, or other substance-drug interactions such as alcohol-drug and tobacco-drug interactions. This review highlights the clinical pharmacokinetic interactions between clinical drugs and commonly used illicit substances such as cannabis, cocaine and 3, 4-Methylenedioxymethamphetamine (MDMA). Rigorous efforts are warranted to further understand the underlying mechanisms responsible for these clinical pharmacokinetic interactions. It is also critical to extend the awareness of the life-threatening adverse interactions to both health care professionals and patients.

In the face of the current Opioid crisis in America killing close to 800,000 people since 2004, we are proposing a novel approach to assist in at least attenuating these unwanted premature deaths. While we applaud the wonderful efforts of our governmental institutes and professional societies (NIDA, NIAAA, ASAM, ABAM ) in their extraordinary efforts in combating this continued dilemma, the current approach is failing, and other alternative approaches should at least be tested. These truths present a serious ethical dilemma to scientists, clinicians and counselors in the Reward Deficiency Syndrome (RDS) treatment community. It is important to realize that the current DSM-5 does not actually accurately display the natural brain reward process. The human brain has not been designed to carve out specific drugs like opioids, alcohol, nicotine, cocaine, benzodiazepines or cannabis and process addictions such as gambling as distinct endophenotypes. This is true in spite of natural ligands for cannabinoids, endorphins, or even benzodiazepines. The most accurate endophenotype is indeed reward dysfunction (e.g hypodopaminergic or hyperdopaminergic). With this mind, we are hereby proposing that the current Medication Assisted Treatment (i.e. 'MAT') expands to needed individuals as an initial "Band-Aid" to reduce harm avoidance, with the long-term goal of prophylaxis. So, to be clear, there may be other promising modalities other than MAT such as repetitive transcranial magnetic stimulation (rTMS), exercise and even new medications with positive allosteric modulators of GABA-A receptors, as well as the highly researched Genetic Addiction Risk Score (GARS) coupled with precision KB220Z. This will induce "dopamine homeostasis" to effectively rebalance and restore healthier brain function by promoting the cross talk between various brain regions (e.g. Nucleus accumbens, cingulate gyrus, hippocampus etc.) resulting in dopamine homeostasis. Our laudable goal is to not only save lives, but to redeem joy and improve the quality of life in the recovery community through scientifically sound natural non-addicting alternatives.

There has been increased interest in the role of cannabis for treating medical conditions. The availability of different cannabis-based products can make the side effects of exposure unpredictable. We sought to conduct a scoping review of systematic reviews assessing benefits and harms of cannabis-based medicines for any condition.A protocol was followed throughout the conduct of this scoping review. A protocol-guided scoping review conduct. Searches of bibliographic databases (e.g., MEDLINE®, Embase, PsycINFO, the Cochrane Library) and gray literature were performed. Two people selected and charted data from systematic reviews. Categorizations emerged during data synthesis. The reporting of results from systematic reviews was performed at a high level appropriate for a scoping review.After screening 1975 citations, 72 systematic reviews were included. The reviews covered many conditions, the most common being pain management. Several reviews focused on management of pain as a symptom of conditions such as multiple sclerosis (MS), injury, and cancer. After pain, the most common symptoms treated were spasticity in MS, movement disturbances, nausea/vomiting, and mental health symptoms. An assessment of review findings lends to the understanding that, although in a small number of reviews results showed a benefit for reducing pain, the analysis approach and reporting in other reviews was sub-optimal, making it difficult to know how consistent findings are when considering pain in general. Adverse effects were reported in most reviews comparing cannabis with placebo (49/59, 83%) and in 20/24 (83%) of the reviews comparing cannabis to active drugs. Minor adverse effects (e.g., drowsiness, dizziness) were common and reported in over half of the reviews. Serious harms were not as common, but were reported in 21/59 (36%) reviews that reported on adverse effects. Overall, safety data was generally reported study-by-study, with few reviews synthesizing data. Only one review was rated as high quality, while the remaining were rated of moderate (n = 36) or low/critically low (n = 35) quality.Results from the included reviews were mixed, with most reporting an inability to draw conclusions due to inconsistent findings and a lack of rigorous evidence. Mild harms were frequently reported, and it is possible the harms of cannabis-based medicines may outweigh benefits.The protocol for this scoping review was posted in the Open Access (https://ruor.uottawa.ca/handle/10393/37247).

Pantothenate kinase-associated neurodegeneration is characterized by severe, progressive dystonia. This study aims to describe the reported usage of cannabis products among children with pantothenate kinase-associated neurodegeneration.A cross-sectional, 37-item survey was distributed in April 2019 to the families of 44 children who participate in a clinical registry of individuals with pantothenate kinase-associated neurodegeneration.We received 18 responses (40.9% response rate). Children were a mean of 11.0 (SD 4.3) years old. The 15 respondents with dystonia or spasticity were on a median of 2 tone medications (range 0-9). Seven children had ever used cannabis (38.9%). The most common source of information about cannabis was other parents. Children who had ever used cannabis were on more tone medications, were more likely to have used opiates, were less likely to be able to roll, and less likely to sit comfortably, than children who had never used cannabis. Four children reported moderate or significant improvement in dystonia with cannabis. Other areas reported to be moderate or significantly improved were pain (n = 3), sleep (n = 4), anxiety (n = 3), and behavior (n = 2). Adverse effects included sadness (n = 1), agitation/behavior change (n = 1), and tiredness (n = 1).Cannabis use was commonly reported among children with pantothenate kinase-associated neurodegeneration whose parents responded to a survey, particularly when many other dystonia treatments had been tried. Physicians should be aware that parents may treat their child with severe, painful dystonia with cannabis. Placebo-controlled studies of products containing cannabidiol and 9-tetrahydrocannabinol are needed for pediatric tone disorders.

Research primarily conducted in Europe find high neighborhood ethnic density (i.e., proportion of own ethnic group) lessens risk of psychotic symptoms among racial and ethnic minorities; however, most studies measure ethnic density through crude demarcations in geographic data only at illness onset which may miss meaningful variation from the perspective of residents. The present study is the first in the U.S. to examine whether changes in perceived ethnic density from childhood are associated with psychotic-like experiences (PLE).A Northeastern U.S. urban undergraduate sample of 1330 racial and ethnic minorities completed a self-report inventory of PLE, the Prodromal Questionnaire, and indicated their racial and ethnic neighborhood composition before and after age 12. One way analyses of covariance (ANCOVA) adjusted for age, family poverty, racial and ethnic group, immigrant status, and lifetime cannabis use, compared PLE across ethnic density categories and change.Racial and ethnic minorities who grew up in a neighborhood (before age 12) predominantly inhabited by a different group of color (e.g., being Black in a predominantly Asian neighborhood) endorsed significantly more PLE than those who grew up in racially concordant, mixed, or predominantly White neighborhoods. In addition, those reporting a change in perceived neighborhood ethnic density after age 12 endorsed significantly more PLE than those reporting no change.Racial dynamics among people of color in urban neighborhood U.S. contexts may create psychological challenges in the social environment. The developmental timing of demographic changes in neighborhoods may influence stress processes that enhance risk for PLE.

The most bioactive ingredient of cannabis (Cannabis sativa or indica) extracts, Δ9-tetrahydrocannabinol (THC), was identified in the 1960s as one of more than 110 phytocannabinoids. It activates receptors of chemically different endogenous ligands (endocannabinoids) that, unlike THC, are metabolized by several enzymes of the endocannabinoid system. Here, the complexity of the plant-derived and endogenous cannabinoids (eCBs) is discussed, to better appreciate the challenge of: (i) dissecting their mutual interactions; (ii) understanding their impact on human pathophysiology; and (iii) exploiting them for human disease. To this aim, missing pieces to the eCB puzzle must be urgently found, by solving the 3D structures of key components, and interrogating noncanonical modes of regulation and trafficking of these lipid signals.

Alcohol and cannabis remain the substances most widely used by adolescents. Better understanding of the dynamic relationship between trajectories of substance use in relation to neuropsychological functioning is needed. The aim of this study was to examine the different impacts of within- and between-person changes in alcohol and cannabis use on neuropsychological functioning over multiple time points.Hierarchical linear modeling examined the effects of alcohol and cannabis use on neuropsychological functioning over the course of 14 years in a sample of 175 adolescents (aged 12-15 years at baseline).Time-specific fluctuations in alcohol use (within-person effect) predicted worse performance across time on the Wechsler Abbreviated Scale of Intelligence Block Design subtest (B = -.05, SE = .02, p = .01). Greater mean levels of percent days of cannabis use across time (between-person effect) were associated with an increased contrast score between Delis-Kaplan Executive Function System Color Word Inhibition and Color Naming conditions (B = .52, SE = .14, p < .0001) and poorer performance over time on Block Design (B = -.08, SE = .04, p = .03). Neither alcohol and/nor cannabis use over time was associated with performance in the verbal memory and processing speed domains.Greater cumulative cannabis use over adolescence may be linked to poorer inhibitory control and visuospatial functioning performance, whereas more proximal increases in alcohol consumption during adolescence may drive alcohol-related performance decrements in visuospatial functioning. Results from this prospective study add to the growing body of literature on the impact of alcohol and cannabis use on cognition from adolescent to young adulthood.

Emerging adulthood is a common and problematic time for alcohol and cannabis use. Emerging adulthood also represents a vulnerable time period for anxiety and depression. Substance use and mental health issues are highly comorbid, yet substance use is commonly neglected in psychiatric care.The goal of this study was to categorize the cannabis and alcohol use patterns of emerging adults in psychiatric care and to evaluate relationships with use-related problems, psychiatric symptomatology, and motives for use.Participants were emerging adults who were consecutive admissions to a young adult psychiatric partial hospital program from 2017 to 2018. Of 318 participants who completed questionnaires, 244 (76.7%) reported cannabis and/or alcohol use in the previous month. Cluster analyses and analysis of variance tests were conducted to categorize and differentiate between participants who reported use.Results from cluster analyses identified 4 categories of use: low cannabis/high alcohol (35.7%), low cannabis/low alcohol (17.6%), high cannabis/low alcohol (29.1%), and high cannabis/high alcohol (17.6%). Individuals in categories with the highest rates of use and co-use reported more alcohol problems (F=24.31, P<0.001), cannabis problems (F=36.75, P<0.001), depression (F=3.60, P=0.01), and motives: social (F=6.12, P<0.001), coping with anxiety (F=20.43, P<0.001), coping with depression (F=17.80, P<0.001), enhancement (F=7.85, P<0.001), and conformity (F=4.92, P<0.01).Clear categories of substance use emerged. Participants who were heavier users were more likely to use to alleviate psychiatric symptomatology, yet they also reported greater psychiatric symptomatology and use-related problems. Among a psychiatric sample of emerging adults, cannabis and alcohol use was common and problematic. Thus, substance use should be evaluated for and, if present, targeted with interventions during psychiatric care.

Beliefs about marijuana use and prevalence of use may be associated with the legalization status of the state of residence. We examined differences in views and rates of use of marijuana among residents in recreationally legal, medically legal, and nonlegal states.We surveyed a nationally representative online panel of US adults (N = 16,280) and stratified results by marijuana legalization status of states. We compared views of residents of recreational states on benefits and risks of marijuana use to residents in other states.The response rate was 56.3% (n = 9003). Residents in recreationally legal states were more likely to believe marijuana could be beneficial for pain management (73% in recreationally legal states, 67% in medically legal states, 63% in nonlegal states; P value: <0.0001), provide relief from stress, anxiety or depression (52% in recreationally legal states, 47% in medically legal states, 46% in nonlegal states; P value: 0.01), and improve appetite (39% in recreationally legal states, 36% in medically legal states, 33% in nonlegal states; P value: <0.009). In addition, residents in recreational states were significantly more likely to believe that smoking 1 marijuana joint a day is somewhat or much safer than smoking 1 cigarette a day (40.8% in recreationally legal states, 39.1% in medically legal states, and 36.1% in nonlegal states; P value: <0.0001). Residents of recreationally and medically legal states were more likely to believe second-hand marijuana smoke was somewhat or much safer than second-hand tobacco smoke (38.3% in recreationally legal states, 38.3% in medically legal states, and 35.7% in nonlegal states; P value: 0.003). Past-year marijuana use in any form (20% in recreational, 14.1% in medical, 12% in nonlegal) and past-year marijuana use of multiple forms (11.1% in recreational, 6.1% in medical, 4.9% in nonlegal) were highest among residents of recreationally legal states. Overall, prevalence of past-year use of any form of marijuana use was more common among residents of recreationally legal states compared with other states (20.3%, confidence interval [CI] 19.5, 21.1 in recreationally legal states; 15.4%, CI 14.7, 16.2 in medically legal states; 11.9%, CI 11.2, 12.6 in nonlegal states).Residents in recreationally legal states were most likely to believe marijuana has benefits, marijuana smoke is safer than tobacco smoke, and have the highest rate of marijuana use. This is cause for concern, given the tide of commercialization, growing number of high-potency cannabis products, and favorable media coverage promoting use for health problems.

Objective: The objectives of the study were to describe the distribution of tetrahydrocannabinol (THC)-influenced drivers in a new Danish 3-level offense system and discuss the consequences of the changed legislation.Methods: By request of the police, blood of individuals suspected of driving under the influence of drugs (DUID) in Funen and Southern Jutland was sampled by medical staff and shipped to the Section of Forensic Toxicology of the University of Southern Denmark in Odense. Samples from individuals suspected for driving under the influence of cannabis (DUIC) were stored at 5 °C prior to immediate analysis, and THC content in whole-blood samples was established by gas chromatography-mass spectrometry analysis. Quantitative results for blood THC levels were available from 2017 and 2018, resulting in 2,206 eligible cases. Data before and after the legal change on December 15, 2017, were extracted from the department's laboratory information management system.Results: With the new graduated sanctions introduced in December 2017, 70% of the DUIC suspects faced milder sanctions. The number of DUIC cases has been increasing and has almost doubled in the last 4 years, from 648 cases in 2015 to 1,206 in 2018. Correspondingly, the total number of DUID cases increased by 80% from 898 cases in 2015 to 1,614 cases in 2018. The concentration of THC in blood was above the legal limit of 0.001 mg/kg in 73% of the cases; 18% had concentrations categorized as low, 32% as medium, and 22% as high.Conclusion: We found that more than two-thirds of the THC offenders faced milder sanctions compared to before the new legislation, suggesting that the new graduated legislation has had a significant impact. The current trend is a steadily increasing number of DUID cases. We believe that the continual increase is caused by a combination of factors, including increased police awareness and training of police personnel along with improved roadside screening abilities.

Ecological stoichiometry represents the balance of nutrient elements under ecological interactions, which are crucial for biogeochemical cycles in ecosystems. Little is known about carbon (C), nitrogen (N), and phosphorus (P) ecological stoichiometry in aboveground biomass, roots, and soil, especially in the subtropical riparian wetlands. Here, eight dominate plant communities in riparian wetlands were chosen, and C, N, and P contents, and C:N:P ratios of aboveground biomass, roots, and soil were investigated. The results demonstrated that plant community had remarkable effects on the C:N:P stoichiometry in aboveground biomass, roots, and soil, which varied widely. C, N, and P concentrations in aboveground biomass were mostly higher than that in roots, while no significant difference was detected in C:N:P ratios. Moreover, there were higher soil C, N, and P contents in Cannabis indica plant communities; while lower soil N:P ratios suggested that riparian wetlands were more susceptible to N limitation, rather than P. Pearson correlation analysis and redundancy analysis (RDA) showed that there were strong associations among C, N, and P contents, and C:N:P ratios in aboveground biomass, roots, and soil, indicating that C, N, and P ecological stoichiometry of aboveground biomass were regulated by soil C, N, and P contents through the roots. In addition, the contents of C and N, and N and P exhibited a strong relationship according to linear regression. These findings suggested that the interactions among the C, N, and P stoichiometry were existed in the plant-soil system.

Restless legs syndrome (RLS) is one of the most disabling and sometimes painful sensorimotor ailment of the nervous system that has only in recent years become more widely accepted as a clinical disorder with its own distinct features. Usually, symptoms respond well to dopamine agonists, anticonvulsants, or opiates, but still a subset of patients remains refractory to medical therapy and/or reports serious side effects. Recently, patients' statement of a remarkable and total remission of RLS symptoms following cannabis use has been reported. Here, we confirm and extend these findings to more patients with RLS. The antinociceptive effect of marijuana has been documented in many painful neurological conditions, and the potential benefit of cannabis use in patients with refractory RLS should therefore be questioned by robust clinical trials.

The number of cannabis users increased up to 188 million users worldwide in 2017. Smoking and vaping are the most common consumption routes with formation of side-stream smoke/vapor and secondhand exposure to cannabinoids has been described in the literature. External contamination of hair by cannabis smoke has been studied but there are no studies on third-hand cannabis exposure due to deposition of smoke or vapor on surfaces. We tested whether cannabinoids could be detected on surfaces and objects in a room where cannabis is vaporized. Surface samples were collected using isopropanol imbued non-woven wipes from hard surfaces and objects. Each surface was swabbed three times with standardized swabbing protocol including three different patterns. Samples were analyzed using LC-ESI-MS/MS in combination with online extraction. THC was detected on 6 samples out of the 15 collected in the study room at quantifiable levels ranging 348-4882 ng/m2. Negative control samples collected from areas outside the study room were all negative. We demonstrated that surfaces exposed to side-stream cannabis vapor are positive for THC at quantifiable levels. This study represents a first step in understanding how side-stream cannabis vapor deposits in the environment and potentially results in a tertiary exposure for users and non-users.

An association between first-episode presentation of bipolar mania and concurrent cannabis use disorder has been well established in the current literature (Bally et al., 2014, Baethge et al., 2008). Previous studies have shown that 30-70% of patients admitted for a first manic episode had concurrent cannabis use (Bally et al., 2014). The exact mechanism of this association has yet to be confirmed.We aim to evaluate the prevalence of cannabis use in patients with bipolar disorder (BD) admitted to UTHealth Harris County Psychiatric Center (HCPC) for a first manic episode.In this retrospective cohort study, 15,969 inpatient records of patients admitted to HCPC between 2012-2013 were examined to identify patients admitted with a first manic episode according to ICD-9 criteria (single episode mania). The prevalence of multiple sociodemographic and clinical variables including cannabis positivity in urine drug screening (UDS) were examined.Twenty patients were admitted for a first manic episode. Half of the patients were females; mean age was 28.65 ± 10.56 years and mean length of stay (LOS) was 7.15 ± 3.72 days. Fifteen patients received a UDS. Of these fifteen, seven were positive for cannabinoids (47%). One patient was positive for phencyclidine (in addition to cannabis) and one patient was positive for amphetamine (but not cannabis).The prevalence of cannabis use was higher in first-episode mania patients compared to the general population. The influence of cannabis on the first episode of mania requires additional study.

In spite of the remarkable achievements in the healthcare sector over recent decades, inequities in accessibility and affordability of these facilities coexist throughout Pakistan. Thus, we aimed to explore and document the cultural knowledge of herbal teas used medicinally by the local community members of Manoor Valley, Pakistan. Field investigations were undertaken during the summer season of 2015-2017, and cultural practices of medicinal plant usage for treating various ailments were gathered through interviews of the local inhabitants. Ethnomedicinal insights of the medicinal plants used in herbal teas were gained with different indexes. Our results revealed 27 plant species, comprising of herbs (70%), shrubs (26%), and trees (4%), which were used for treating 21 diseases. Plants belonged to 18 families: Asteraceae and Lamiaceae were the leading families used for treating diseases. Diarrhea and gas troubles were the most frequent diseases. Based on indexes values, Cannabissativa was the dominant species used. The results revealed that 57% of medicinal uses are new to literature. This ethnomedicinal study is providing the first insights into the traditional medication system of Lesser Himalaya, Pakistan, through ethnomedicinal teas.

Elucidation of Cannabis composition is required to evaluate the potential of this plant for pharmacological uses, but also for implementation in breeding programs with agronomical purposes. The aim of the present study was to develop a method for untargeted analysis of polar and non-polar Cannabis extracts. For this purpose, extracts from 17 cultivars of Cannabis sativa L. were analyzed by gas chromatography-time-of-flight/mass spectrometry (GC-TOF/MS) and liquid chromatography quadrupole time-of-flight tandem mass spectrometry (LC-QTOF MS/MS) in high resolution mode. One hundred sixty-nine compounds were identified in the extracts by searching MS and MS/MS information. Among identified families, there were mainly cannabinoids, terpenoids, lipids and flavonoids, but also some interesting compounds such as amino and organic acids, among others. Relative contents of terpenoids and cannabinoids in the same cultivars grown in greenhouse and field were compared. Compositional differences in the profile of terpenoids and cannabinoids between both types of grown conditions were found.

Limited data suggest that cannabidiol (CBD) may be effective for treatment of refractory infantile spasms (IS). This study was designed to more rigorously evaluate the efficacy and safety of synthetic CBD in the treatment of IS.Children six to 36 months of age with IS that failed treatment with both adrenocorticotropic hormone (ACTH) and vigabatrin (VGB) were eligible for enrollment. Children receiving clobazam were excluded. After baseline overnight video-electroencephalography (vEEG) to confirm diagnosis and ascertain hypsarrhythmia, patients were treated with synthetic CBD oral solution (20 mg/kg/day). Overnight video-EEG was repeated after 14 days, and both baseline and repeat video-EEGs were completely de-identified and reviewed in a pairwise fashion by an independent, blinded pediatric electroencephalographer. The primary efficacy endpoint was freedom from spasms and hypsarrhythmia on day 14.Nine patients were enrolled, comprising an older (median age = 23 months) cohort with long-standing IS (median duration = 13 months) and numerous prior treatment failures (median = 6). One patient responded to therapy and eight patients exhibited neither clinical nor electrographic response.The immediate but temporary response in a single patient suggests that CBD oral solution is not particularly effective in highly refractory cases, but may, nevertheless, be effective in younger patients with shorter durations of IS. Further study, examining both short- and long-term outcomes, is warranted to further evaluate the efficacy and safety of CBD oral solution in the treatment of IS.

Dance teachers (DTs) give lessons on various professional and amateur genres. Up to the present, little has been known on health-related behavior regarding the consumption of substances such as inhalant and synthetic substances, cocaine, cannabis/marijuana (c/m), anabolic steroids and naturally occurring hallucinogens in dance teachers.To analyze the consumption of these substances as well as to determine influencing variables due to their role model function (educational level, prevalence of injuries, BMI and income).N = 236 (m: n = 53, f: n = 183) professional DTs participated in the single cross-sectional cohort study.The majority of DTs had a single or occasional use of the tested substances. This coincides with the results of the general population. C/m was the most frequently consumed substance with a prevalence of up to 40.1% (m). Only a few significant gender-specific differences were observed. There were weak gender-specific correlations between the consumption of substances and educational level (f) and income (m and f) or injuries (f).Due to the specific occupational stress DTs are exposed to, a use of substances would be conceivable. However, apart from cannabis/marijuana (c/m), the consumption of psychoactive substances in DTs seems to be negligible. However, attention should be paid to the significant proportion of dance teachers having tried out substances.

Borderline personality disorder and substance use disorder co-occur at a high rate. However, little is known about the mechanisms driving this association. This study examined substance use motives for 3 common substance use disorders among 193 individuals in substance use disorder treatment. We found that the coping motive consistently mediated the relationship between borderline personality and alcohol, cannabis, and prescription opioid use disorders. For this substance use disorder treatment sample, our findings support the self-medication model of substance use, and that interventions aimed at coping-related substance use would be helpful among these patients. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

With legalization efforts across the United States, cannabis use is becoming increasingly mainstream. Various studies have documented the effects of acute and chronic cannabis use on brain structure and cognitive performance, including within the frontal executive control network, but little attention has been given to the effects on the cerebellum. Recent evidence increasingly points to the role of the cerebellum in various nonmotor networks, and the cerebellum's expression of cannabinoid receptors may pose particular vulnerabilities to the consequences of cannabis use. Using a combined approach of resting-state functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI), the present study aims to assess how cannabis use relates to the cerebellum's intrinsic functional connectivity and underlying white matter structure and whether these properties are associated with craving or severity of cannabis use. Resting-state fMRI and DTI data, as well as self-reports of substance use history, were analyzed from a sample of 26 adults at risk for cannabis use disorder (CUD) and an age- and sex-matched comparison group of 25 cannabis-naïve adults (control). Results demonstrated that individuals at risk for a CUD showed key differences in cerebellar functional connectivity, with specific impacts on the dorsal attention and default mode networks. In addition, group differences in white matter were localized to the middle cerebellar peduncle (MCP), with a relationship between lower MCP diffusivity and higher levels of self-reported craving. These findings lend further support to the cerebellum's role in key cognitive networks and potential consequences for substance use disorders.

Prolonged use of cannabis, the most widely used illicit drug worldwide, has been consistently associated with impairment in memory and verbal learning. Although the neurophysiological underpinnings of these impairments have been investigated previously using functional magnetic resonance imaging (fMRI), while performing memory tasks, the results of these studies have been inconsistent and no clear picture has emerged yet. Furthermore, no previous studies have investigated trial-by-trial learning.We aimed to investigate the neural underpinnings of impaired verbal learning in cannabis users as estimated over repeated learning trials.We studied 21 adolescent-onset regular cannabis users and 21 non-users using fMRI performed at least 12 h after last cannabis use, while they performed a paired associate verbal learning task that allowed us to examine trial-by-trial learning. Brain activation during repeated verbal encoding and recall conditions of the task was indexed using the blood oxygen level-dependent haemodynamic response fMRI signal.There was a significant improvement in recall score over repeated trials indicating learning occurring across the two groups of participants. However, learning was significantly slower in cannabis users compared to non-users (p = 0.032, partial eta-squared = 0.108). While learning verbal stimuli over repeated encoding blocks, non-users displayed progressive increase in recruitment of the midbrain, parahippocampal gyrus and thalamus (p = 0.00939, partial eta-squared = 0.180). In contrast, cannabis users displayed a greater but disrupted activation pattern in these regions, which showed a stronger correlation with new word-pairs learnt over the same blocks in cannabis users than in non-users.These results suggest that disrupted medial temporal and midbrain function underlie slower learning in adolescent-onset cannabis users.

The prevalence and effects of cigarette smoking and cannabis use in persons with congenital heart disease (CHD) are poorly understood. We (1) described the prevalence of cigarette smoking, cannabis consumption, and co-use in adults with CHD; (2) investigated intercountry differences; (3) tested the relative effects on physical functioning, mental health, and quality of life (QOL); and (4) quantified the differential effect of cigarette smoking, cannabis use, or co-use on those outcomes.APPROACH-IS was a cross-sectional study, including 4028 adults with CHD from 15 countries. Patients completed questionnaires to measure physical functioning, mental health, and QOL. Smoking status and cannabis use were assessed by means of the Health Behaviour Scale-Congenital Heart Disease. Linear models with doubly robust estimations were computed after groups were balanced with the use of propensity weighting.Overall, 14% of men and 11% of women smoked cigarettes only; 8% of men and 4% of women consumed cannabis only; and 4% of men and 1% of women used both substances. Large intercountry variations were observed, with Switzerland having the highest prevalence for smoking cigarettes (24% of men, 19% of women) and Canada the highest for cannabis use (19% of men, 4% of women). Cigarette smoking had a small negative effect on patient-reported outcomes, and the effect of cannabis was negligible. The effect of co-use was more prominent, with a moderate negative effect on mental health.We found significant intercountry variability in cigarette and cannabis use in adults with CHD. Co-use has the most detrimental effects on patient-reported outcomes.

Cannabis use and cannabis use disorder (CUD) is increased in patients with schizophrenia. It is important to establish if this is explained by non-causal factors, such as shared genetic vulnerability. We aimed to investigate whether the polygenic risk scores (PRS) for schizophrenia and other psychiatric disorders would predict CUD in controls, patients with schizophrenia, and patients with other psychiatric disorders.We linked nationwide Danish registers and genetic information obtained from dried neonatal bloodspots in an observational analysis. We included people with schizophrenia, other psychiatric disorders, and controls. The exposures of interest were the PRS for schizophrenia, attention-deficit hyperactivity disorder (ADHD) autism spectrum disorder, and anorexia nervosa. The main outcome of interest was the diagnosis of CUD.The study included 88 637 individuals. PRS for schizophrenia did not predict CUD in controls [hazard ratio (HR) = 1.16, 95% CI 0.95-1.43 per standard-deviation increase in PRS, or HR = 1.47, 95% CI 0.72-3.00 comparing highest v. remaining decile], but PRS for ADHD did (HR = 1.27, 95% CI 1.08-1.50 per standard-deviation increase, or HR = 2.02, 95% CI 1.27-3.22 for the highest decile of PRS). Among cases with schizophrenia, the PRS for schizophrenia was associated with CUD. While CUD was a strong predictor of schizophrenia (HR = 4.91, 95% CI 4.36-5.53), the inclusion of various PRS did not appreciably alter this association.The PRS for schizophrenia was not associated with CUD in controls or patients with other psychiatric disorders than schizophrenia. This speaks against the hypothesis that shared genetic vulnerability would explain the association between cannabis and schizophrenia.

Many patients have reported that they decrease their use of opioids after starting medical cannabis (MC) but less is known for alcohol. The objective of this exploratory study was to identify any factors which differentiate alcohol abaters from those that do not modify their alcohol use after starting MC (non-abaters). Comparisons were made to identify any demographic, dosing, or health history characteristics which differentiated alcohol abaters (N = 47) from non-abaters (N = 65). Respondents selected from among a list of 37 diseases/health conditions (e.g. diabetes, sleep disorders). Abaters and non-abaters were indistinguishable in terms of sex, age, or prior drug history. A greater percentage of abaters (59.6%) than non-abaters (40.6%, p < .05) reported using MC two or more times per day. Abaters were more likely to be employed (68.1%) than non-abaters (51.1%, p < .05). Abaters also reported having significantly more health conditions and diseases (3.3 ± 2.0) than non-abaters (2.4 ± 1.4, p < .05). This small study offers some insights into the profile of patients whose self-reported alcohol intake decreased following initiation of MC. Additional prospective or controlled research into the alcohol abatement phenomenon following MC may be warranted.

The global population is aging, and as the population ages, high-risk alcohol and other drug use, particularly cannabis and prescription medications, is growing among older adults (OA). OA, defined here as 50 years of age and older, have a number of unique vulnerabilities to drug and alcohol use due to both biological as well as psychosocial factors compared to younger adults. Understanding the wide spectrum of these vulnerabilities is important to assessment, diagnosis, and intervention. Specific techniques, assessment tools, and interventions known to be effective in OA are reviewed.

Culpability analysis was conducted on 5000 drivers injured as a result of a vehicular collision and in whom comprehensive toxicology testing in blood was conducted. The sample included 1000 drivers for each of 5 years from approximately 5000-6000 drivers injured and taken to hospital in the State of Victoria. Logistic regression was used to investigate differences in the odds of culpability associated with alcohol and drug use and other selected crash attributes using the drug-free driver as the reference group. Adjusted odds ratios were obtained from multivariable logistic regression models in which other potentially explanatory driver and crash attributes were included. Drivers with alcohol present showed large increases in the odds of culpability similar to that seen in other studies investigating associations between blood alcohol concentration and crash risk. Methylamphetamine also showed a large increase in the odds of culpability (OR 19) compared to the reference group at both below and above 0.1 mg/L, whereas those drivers with Δ9-tetrahydrocannabinol (THC) present showed only modest increase in odds when all concentrations were assessed (OR 1.9, 95 %CI 1.2-3.1). Benzodiazepines in drivers also gave an increase in odds (3.2, 95 %CI 1.6-6.1), but not other medicinal drugs such as antidepressants, antipsychotics and opioids. Drivers that had combinations of impairing drugs generally gave a large increase in odds, particularly combinations of alcohol with THC or benzodiazepines, and those drivers using both THC and methamphetamine.

Recovery high schools (RHS) provide a supportive educational and therapeutic environment for students subsequent to treatment for substance use disorders (SUDs). Most students served by RHSs have concurrent mental health disorders and are at risk for school failure or dropout and substance use relapse.The central question addressed is whether RHSs are economically efficient alternatives to other high school settings for students in recovery. The aim is to estimate the incremental cost-benefit of RHSs.A quasi-experimental non-equivalent pretest-posttest comparison group design was used. We compared substance use and educational outcomes for adolescents who had received specialty SUD treatment; 143 who enrolled in an RHS were compared to 117 who enrolled in a non-RHS school. Groups were balanced by use of a propensity score to drop students who were not similar to those in the other group. The propensity score was also used as a covariate in multiple regression to estimate cost and outcome parameters and standard errors. To take account of uncertainties in impacts and shadow prices, we used Monte Carlo simulations to estimate the distribution of incremental benefits of RHS relative to non-RHS schooling.Two beneficial impacts of statistical and substantive importance were identified: increased probability of high school graduation and increased sobriety. RHS students had significantly (p<.05) less substance use during the study period -- at 12-month follow-up, 55% of RHS and 26% of comparison students reported 3 month abstinence from alcohol and drugs. Urinalysis confirmed abstinence from THC (cannabis) for 68% of RHS versus 37% of comparison students. RHS students' high school graduation rates were 21 to 25 percentage points higher than comparison students. Adopting a societal perspective, incremental benefits of RHSs were estimated by monetizing the increased probability of high school graduation and comparing it to incremental costs. Mean net benefits ranged from USD16.1 thousand to USD51.9 thousand per participant; benefit-to-cost ratios ranged from 3.0 to 7.2.Monetizing the benefits and the incremental costs of RHS relative to conventional schooling show substantial positive net benefits from RHS participation. Two factors lend credibility to the results. First, the RHS improvement in substance use indicates a mechanism through which the increased probability of high school graduation can plausibly occur. Second, the estimated increases in the probability of high school graduation were large and statistically significant. As the productivity gains from high school graduation are also large, the dominant benefit category is very plausible. Limitations include the non-randomized design; selection bias into the study conditions not fully controlled by the propensity scores; generalizability only to young people with treated behavioral health disorders; lack of estimates for direct monetization of reduced substance use among adolescents; possible attenuation of the value of education among individuals with behavioral health issues; and uncertainty in calculation of school costs.This research provides evidence that the recovery high school model provides cost beneficial support for high school students after primary SUD treatment. The students who enroll in RHSs typically have co-occurring mental health and substance use disorders, adding complexity to their continuing care. Funding policies recognizing the multiple systems of care (behavioral health, education, child and family services, juvenile justice) responsible for these young people are called for.

Cannabis - including blunts (cannabis rolled in tobacco-containing cigar casing) - is commonly the first substance used among adolescents, and may increase the likelihood of subsequent initiation of combustible tobacco products.Data were pooled from two prospective studies of adolescents in California and Connecticut (total N=4,594). Logistic regression models assessed the association of baseline ever blunt use and ever non-blunt cannabis use (vs. never cannabis use) with subsequent initiation of any combustible tobacco-only product (i.e., cigarettes, cigars, or cigarillos) by one-year follow-up after adjustment for demographic characteristics and other tobacco product use at baseline. We also assessed whether estimates differed by prior e-cigarette or hookah use at baseline.Among never combustible tobacco-only product users (N=2,973), 221 (7.4%) had ever used a blunt and 114 (3.8%) had ever used only non-blunt cannabis at baseline. Blunt use (adjusted odds ratio (AOR)=1.98, 95% confidence interval (CI): 1.30, 3.01) and non-blunt cannabis use (AOR=2.38, 95% CI: 1.41, 4.00) were independently associated with greater odds of combustible tobacco-only product initiation by follow-up. Among those who had not tried e-cigarettes or who had not tried hookah, blunt use and non-blunt cannabis use were associated with significantly increased odds of combustible tobacco product initiation; among those who had tried e-cigarettes or hookah, the association was not significant.We found blunt and non-blunt cannabis use to be associated with subsequent combustible tobacco-only product initiation, particularly among adolescents who had not also tried other products containing nicotine.

Despite improvements in medical care, patients with advanced cancer still experience substantial symptom distress. There is increasing interest in the use of medicinal cannabinoids, but there is little high quality evidence to guide clinicians. This study aims to define the role of cannabidiol (CBD) in the management of symptom burden in patients with advanced cancer undergoing standard palliative care.This study is a multicentre, randomised, placebo controlled, two arm, parallel trial of escalating doses of oral CBD. It will compare efficacy and safety outcomes of a titrated dose of CBD (100 mg/mL formulation, dose range 50 mg to 600 mg per day) against placebo. There is a 2-week patient determined titration phase, using escalating doses of CBD or placebo to reach a dose that achieves symptom relief with tolerable side effects. This is then followed by a further 2-week assessment period on the stable dose determined in collaboration with clinicians.A major strength of this study is that it will target symptom burden as a whole, rather than just individual symptoms, in an attempt to describe the general improvement in wellbeing previously reported by some patients in open label, non controlled trials of medicinal cannabis. Randomisation with placebo is essential because of the well-documented over reporting of benefit in uncontrolled trials and high placebo response rates in cancer pain trials. This will be the first placebo controlled clinical trial to evaluate rigorously the efficacy, safety and acceptability of CBD for symptom relief in advanced cancer patients. This study will provide the medical community with evidence to present to patients wishing to access medicinal cannabis for their cancer related symptoms.ALCTRN12618001220257 Registered 20/07/2018.

Background: Deceptive responding during eligibility screening presents a significant concern for assessing inclusion/exclusion criteria. This problem is compounded in settings for which biomarkers or other objective verification (e.g., urinalysis) are not feasible.Objectives: Introduce and describe content-knowledge questionnaires as an objective method for collaterally assessing study eligibility.Methods: Participants (N = 3772; 66.1% female) recruited using the crowdsourcing resource Amazon Mechanical Turk (mTurk) completed a Cannabis Knowledge Questionnaire (CKQ). The CKQ contained four-items indexing knowledge of typical cannabis costs, weights, and terminology. Self-reported cannabis use history was collected and compared to individual item and total scale scores. A separate in-laboratory assessment evaluated participants during in-person screening for cannabis, alcohol, and cocaine research protocols (N = 43).Results: Good internal consistency (α = .74) was observed. The most common correctly answered question was about dabbing (41.4%) followed by cannabis cost (37.6%), hybrid strains (36.6%), and estimated weight (29.7%). Current cannabis use was associated with large effect size increases in the rate of correct responses (RR = 3.64) as well as odds of a correct response on individual items (OR = 5.88-21.48). In the laboratory study, participants with a positive urine drug test for cannabis or those reporting lifetime regular cannabis use scored higher than those without this history (RR = 1.89-2.61).Conclusion: These findings highlight the efficiency and efficacy of including content-knowledge questionnaires for collateral assessment of study eligibility, especially when biomarkers are not possible. Future studies will be useful for extending this initial demonstration to alternative settings and substances.

Epilepsy is a neurological disorder that affects approximately 50 million people worldwide. There is currently no definitive epilepsy cure. However, in recent years, medicinal cannabis has been successfully trialed as an effective treatment for managing epileptic symptoms, but whose mechanisms of action are largely unknown. Lately, there has been a focus on neuroinflammation as an important factor in the pathology of many epileptic disorders. In this literature review, we consider the links that have been identified between epilepsy, neuroinflammation, the endocannabinoid system (ECS), and how cannabinoids may be potent alternatives to more conventional pharmacological therapies. We review the research that demonstrates how the ECS can contribute to neuroinflammation, and could therefore be modulated by cannabinoids to potentially reduce the incidence and severity of seizures. In particular, the cannabinoid cannabidiol has been reported to have anti-convulsant and anti-inflammatory properties, and it shows promise for epilepsy treatment. There are a multitude of signaling pathways that involve endocannabinoids, eicosanoids, and associated receptors by which cannabinoids could potentially exert their therapeutic effects. Further research is needed to better characterize these pathways, and consequently improve the application and regulation of medicinal cannabis.

Background: Valid assessment of adolescent substance use is important in both research and clinical applications. However, the optimal approach to assessing adolescent use remains controversial, particularly with regard to the use of parent-reported measures. Methods: Using a systematic review of existing literature, we sought to evaluate the utility of parent measures of adolescent alcohol and cannabis use by examining their correspondence with self-report measures. Furthermore, we investigated study-related variables that may be associated with differing levels of parent-child correspondence. Relevant articles were identified using a systematic search across multiple databases. Results: The review revealed generally poor agreement between parent and adolescent reports of alcohol and cannabis use. Parents consistently underestimated use and problems associated with use when compared with adolescents. Community-based (versus clinical) samples, reporting regarding alcohol (versus cannabis), and reporting problems associated with use (versus reports of use/nonuse) were each associated with lower levels of parent-child agreement. Conclusions: Recommendations for the optimal use of parent measures of adolescent substance use are provided.

The prevalence of drug use during pregnancy continues to increase despite the associated serious adverse obstetrical outcomes, including increased risk of miscarriage, fetal growth restriction, brain development impairment, neonatal abstinence syndrome (NAS), preterm delivery, and stillbirths. Monitoring drug use during pregnancy is crucial to limit prenatal exposure and provide suitable obstetrical health care. The authors reviewed published literature reporting the concentrations of common drugs of abuse and new psychoactive substances, such as synthetic cathinones and synthetic opioids, new psychoactive substances, and their metabolites using unconventional matrices to identify drug use during pregnancy and improve data interpretation.A literature search was performed from 2010 to July 2019 using PubMed, Scopus, Web of Science scientific databases, and reports from international institutions to review recently published articles on heroin, cocaine, amphetamine, methamphetamine, synthetic cathinone, and synthetic opioid monitoring during pregnancy.Meconium has been tested for decades to document prenatal exposure to drugs, but data regarding drug concentrations in amniotic fluid, the placenta, the umbilical cord, and neonatal hair are still lacking. Data on prenatal exposure to new psychoactive substances are limited.Maternal hair testing is the most sensitive alternative matrix for identifying drug use during pregnancy, while drug concentrations in the meconium, placenta, and umbilical cord offer the identification of prenatal drug exposure at birth. Adverse developmental outcomes for the infant make it critical to promptly identify maternal drug use to limit fetal exposure, or if determined at birth, to provide resources to the exposed child and family. Alternative matrices offer choices for monitoring and challenge laboratories to deliver highly sensitive and specific analytical methods for detection.

We aimed to describe and correlate the hospital panorama of psychotic disorders (PD) with cannabis use (CU) trends in all Portuguese public hospitals.We conducted a retrospective observational study that analysed all hospitalizations that occurred in Portuguese public hospitals from 2000 to 2015. Hospitalizations with a primary diagnosis of PD or schizophrenia were selected based on Clinical Classification Software diagnostic single-level 659. Episodes associated with CU were identified by the International Classification of Diseases Version 9, Clinical Modification code 304.3/305.2 that correspond to cannabis dependence/cannabis abuse.The number of hospitalizations with a primary diagnosis of PD and schizophrenia associated with CU rose 29.4 times during the study period, from 20 to 588 hospitalizations yearly (2000 and 2015, respectively) with a total of 3,233 hospitalizations and an average episode cost of €3,500. Male patients represented 89.8% of all episodes, and the mean/median age at discharge were 30.66/29.00 years, respectively. From all hospitalizations with a primary diagnosis of PD or schizophrenia, the ones with a secondary diagnosis of CU rose from 0.87% in 2000 to 10.60% in 2015.The increase on secondary diagnosis coding and the change on cannabis patterns of consumption in Portuguese population with an increasing frequency of moderate/high dosage cannabis consumers may explain the rise on PD hospitalizations.

Over the last decade, there have been a number of changes in the Canadian landscape - the deconstruction of alcohol policy in some provinces, the legalization of cannabis, increased availability of gambling options, and the increase in opioid use and its associated problems. Have there been concomitant changes in societal images of addictions?A general population survey on societal images of addictions was conducted in multiple countries in 2008 - Finland, Sweden, Canada (Canadian sample size: N = 864; 40% response rate), and part of Russia (St Petersburg). We repeated the same survey in 2018 in Canada (N = 813; response rate = 23%). The survey assessed perceptions of the seriousness of different issues to society - including items about alcohol, tobacco, marijuana, gambling, misuse of medical drugs, and drugs like amphetamine, cocaine, or heroin - among other items (e.g., pollution, violent crime, prostitution).There were increases in perceptions of the seriousness of misuse of medical drugs (p = .001), of illicit drugs (p = .005), ratings of the seriousness of cannabis use (p = .02), and a decrease in ratings of gambling as a social problem (p = .04). Ratings of the seriousness of alcohol and tobacco as social problems did not display significant changes over time (p > .05).There has been some variation in societal perceptions of the seriousness of different addictions. Increases in perceptions of the seriousness of misusing medical drugs and the use of illicit drugs may reflect increases in societal concerns about opioid use and its associated problems. Despite substantial changes in alcohol control policies, the legalization of cannabis, and the increased availability of options for gambling, there appears to be very little associated change in societal perceptions regarding these addictive behaviours.

In several countries, especially in Africa, the dominant method of heroin intake is smoking a joint of cannabis laced with heroin. There is no data exploring the impact of smoking heroin with cannabis on treatment outcomes.To compare treatment outcomes between people who inject heroin and people who smoke heroin with cannabis.Three hundred heroin users were assessed on admission to inpatient rehabilitation and after treatment. We compared drug use, psychopathology, criminality, social functioning and general health between heroin injectors and heroin-cannabis smokers at treatment entry, and at 3 and 9 months after rehabilitation.The sample comprised 211 (70.3%) heroin-cannabis smokers and 89 (29.7%) heroin injectors. Eighty-four percent were followed up at 3 months and 75% at 9 months. At 9 months, heroin-cannabis smokers had a higher proportion of those who relapsed to heroin use compared with intravenous (IV) users (p = 0.036). The median number of heroin use episodes per day was lower for IV users than heroin-cannabis smokers at both follow-up points (p = 0.013 and 0.0019). A higher proportion of IV users was HIV positive (p = 0.002). There were no significant differences in psychopathology, general health, criminality and social functioning between IV users and heroin-cannabis smokers at all three time points.Heroin users who do not inject drugs but use other routes of administration may have increased risk for relapse to heroin use after inpatient rehabilitation and should therefore have equal access to harm reduction treatment services. Advocating a transition from injecting to smoking heroin in an African context may pose unique challenges.

1) To investigate whether genetic liability to attention-deficit/hyperactivity disorder (ADHD), indexed by polygenic risk scores for ADHD (PRS-ADHD), is associated with substance use disorders (SUD) in individuals with ADHD. 2) To investigate whether other individual- or family-related risk factors for SUD could mediate or confound this association.Population-based cohort study SETTING AND PARTICIPANTS: ADHD cases in the iPSYCH sample (a Danish case-cohort sample of genotyped cases with specific mental disorders), born in Denmark between 1981 and 2003 (N = 13 116). Register-based information on hospital diagnoses of SUD was available until December 31, 2016.We estimated odds ratios (ORs) with 95% confidence intervals (CIs) for any SUD as well as for different SUD types (alcohol, cannabis, and other illicit drugs) and severities (use, abuse, and addiction), with effect sizes corresponding to a comparison of the highest PRS-ADHD decile to the lowest.PRS-ADHD were associated with any SUD (OR = 1.30, 95% CI: 1.11-1.51). Estimates were similar across different types and severity levels of SUD. Other risk factors for SUD (male sex, age at ADHD diagnosis, comorbid conduct problems, and parental factors including SUD, mental disorders, and socio-economic status) were independently associated with increased risk of SUD. PRS-ADHD explained a minor proportion of the variance in SUD (0.2% on the liability scale) compared to the other risk factors. The association between PRS-ADHD and any SUD was slightly attenuated (OR = 1.21, 95% CI: 1.03-1.41) after adjusting for the other risk factors for SUD. Furthermore, associations were nominally higher in females than in males (ORfemales  = 1.59, 95% CI: 1.19-2.12, ORmales  = 1.18, 95% CI: 0.98-1.42).A higher genetic liability to attention-deficit/hyperactivity disorder appears to be associated with higher risks of substance use disorders in individuals with attention-deficit/hyperactivity disorder.

Potassium is involved in regulation of multiple developmental, physiological, and metabolic processes in plants, including photosynthesis and water relations. We lack information about the response of medical cannabis to mineral nutrition in general, and K in particular, which is required for development of high-grade standardized production for the medical cannabis industry. The present study investigated the involvement of K nutrition in morphological development, the plant ionome, photosynthesis and gas-exchange, water relations, water use efficiency, and K use efficiency, comparatively for two genotypes of medical cannabis, under a long photoperiod. The plants were exposed to five levels of K (15, 60, 100, 175, and 240 ppm K). Growth response to K inputs varied between genotypes, revealing genetic differences within the Cannabis sativa species to mineral nutrition. Fifteen ppm of K was insufficient for optimal growth and function in both genotypes and elicited visual deficiency symptoms. Two hundred and forty ppm K proved excessive and damaging to development of the genotype Royal Medic, while in Desert Queen it stimulated rather than restricted shoot and root development. The differences between the genotypes in the response to K nutrition were accompanied by some variability in uptake, transport, and accumulation of nutrients. For example, higher levels of K transport from root to the shoot were apparent in Desert Queen. However, overall trends of accumulation were similar for the two genotypes demonstrating competition for uptake between K and Ca and Mg, and no effect on N and P uptake except in the K-deficiency range. The extent of accumulation was higher in the leaves > roots > stem for N, and roots > leaves > stem for P. Surprisingly, most micronutrients (Zn, Mn, Fe, Cu, Cl) tended to accumulate in the root, suggesting a compartmentation strategy for temporary storage, or for prevention of access concentrations at the shoot tissues. The sensitivity of net-photosynthetic rate, gas exchange, and water use efficiency to K supply differed as well between genotypes. The results suggest that growth reduction under the deficient supply of 15 ppm K was mostly due to impact of K availability on water relations of the tissue and transpiration in Royal Medic, and water relations and carbon fixation in Desert Queen.

Recent research has fueled a debate concerning the role of nicotine in the emergence of schizophrenia. The three main hypotheses are: (a) the self-medication effect, (b) the causal relationship hypothesis, or (c) the shared diathesis hypothesis. To explore this role, the study of nicotine consumption during the initial prodromal phase of schizophrenia offers important opportunities. In the present work, 10 relevant studies are reviewed, out of 727 retrieved citations, in order to address questions regarding the prevalence of smoking in the prodromal period, the time of smoking initiation, existing patterns of tobacco use in relation with the escalation of prodromal symptoms into first psychotic episode, and potential differences in symptomatology between smokers and nonsmokers. Even though there was considerable heterogeneity among studies, relevant findings are discussed. Prevalence of nicotine use during the prodromal period was reported to be 16.6-46%. Tobacco use was found to be taken up most often before or during the prodromal period of schizophrenia. Even though a protective role of smoking has been reported by one study, other studies report an increased risk for psychosis, with hazard ratios 2.77 (95% CI: 2.34-3.43) and 2.21 (95% CI: 1.11-4.42) for female and male heavy smokers (11-20 and >20 cigarettes/day), respectively. In a different study, the risk of onset was associated with the progressive use of cannabis and tobacco prior to onset, particularly with rapid escalation to the highest levels of use. Also, nicotine use in ultra high risk (UHR) for developing psychosis subjects is associated with elevated cognitive performance, namely better processing speed, visual learning, and spatial working memory. As a conclusion, it appears that evidence accumulates supporting a possible etiologic role of smoking, in the emergence of schizophrenia along with diverse effects on patients' symptomatology, already demonstrable at the prodromal phase. Future research employing better-defined criteria should further explore the patterns of use and effects of nicotine during the schizophrenia prodrome.

This study attempted to provide the effects and mechanisms of two cannabinoids, O-1602 and cannabidiol (CBD), on colonic motility of 2,4,6-trinitro-benzene sulfonic acid (TNBS) colitis.TNBS was used to induce the model of motility disorder. G protein-coupled receptor 55 (GPR55) expression was detected using real-time PCR and immunohistochemistry in colon. Pro-inflammatory cytokines and myeloperoxidase were also measured. The colonic motility was measured by upper GI transit in vivo and recorded using electrical stimulation organ bath technique in vitro. Freshly isolated smooth muscle from the rat colon were applied to determine the membrane potential and Ca2+ -ATPase activity, respectively.CBD or O-1602 separately improved inflammatory conditions significantly in TNBS-induced colitis rats. However, sole CBD pretreatment reduced GPR55 expression, which was up-regulated in TNBS colitis. O-1602 and CBD each lowered MPO and IL-6 levels remarkably in TNBS colitis, while TNF-α levels experienced no change. CBD rescued the downward colonic motility in TNBS colitis in vivo; however, it decreased the upward contraction of the smooth muscle strip under electrical stimulation in vitro. Pretreatment with CBD prevented against TNBS-induced changes of Ca2+ -ATPase activity of smooth muscle cells. However, membrane potential of the smooth muscle cells decreased by TNBS experienced no change after O-1602 or CBD import.The present study suggested that CBD participated in the regulation of colonic motility in rats, and the mechanisms may be involved in the regulation of inlammatory factors and Ca2+ -ATPase activity through GPR55.

Adolescence represents a highly sensitive period of mammalian neurodevelopment wherein critical synaptic and structural changes are taking place in brain regions involved in cognition, self-regulation and emotional processing. Importantly, neural circuits such as the mesocorticolimbic pathway, comprising the prefrontal cortex, sub-cortical mesolimbic dopamine system and their associated input/output centres, are particularly vulnerable to drug-related insults. Human adolescence represents a life-period wherein many individuals first begin to experiment with recreational drugs such as nicotine and cannabis, both of which are known to profoundly modulate neurochemical signalling within the mesocorticolimbic pathway and to influence both long-term and acute neuropsychiatric symptoms. While a vast body of epidemiological clinical research has highlighted the effects of adolescent exposure to drugs such as nicotine and cannabis on the developing adolescent brain, many of these studies are limited to correlative analyses and rely on retrospective self-reports from subjects, making causal interpretations difficult to discern. The use of pre-clinical animal studies can avoid these issues by allowing for precise temporal and dose-related experimental control over drug exposure during adolescence. In addition, such animal-based research has the added advantage of allowing for in-depth molecular, pharmacological, genetic and neuronal analyses of how recreational drug exposure may set up the brain for neuropsychiatric risk. This review will explore some of the advantages and disadvantages of these models, with a focus on the common, divergent and synergistic effects of adolescent nicotine and cannabis exposure on neuropsychiatric risk.

Alcohol consumption is common among young people. We performed a preliminary cross-sectional study among students (aged 18-30 years) enrolled for the academic year 2018-2019 at the Faculty of Nursing, University of Cantabria (Spain). We collected information on psychological and sociographic factors, tobacco and cannabis uses, and levels of physical activity by AUDIT questionnaires and in person interviews. The aim of our study was to assess the potential of binge drinking (BD) to adversely affect memory and executive function. We recruited 103 students, of whom 85% were female. The alcohol use pattern of slightly more than one-half of the total population was classified as BD. Among BD students, one-fourth were smokers, and nearly one-third had tried cannabis. The mean onset for alcohol use was 15.11 years. Despite our relatively small sample size, our results show that there are strong relationships between BD and both smoking and cannabis use.

Cannabis has gained widespread public advocacy since its legalization in several states with recent evidence suggesting that its self-reported use has increased in patients undergoing a primary total joint arthroplasty. The endocannabinoid system has been proposed to play a role in decreasing the inflammatory cascade and enhancing pain management. For these reasons, interest has emerged in the orthopaedic community as a potential treatment or adjunct to treatment in many musculoskeletal conditions. However, the evidence to date is scant and precludes recommendations for its widespread use. Given the current paucity of evidence in the orthopaedic cohort, future research is warranted in this area to determine the efficacy and safety before endorsements can be made by orthopaedic surgeons.

Objectives To estimate the prevalence of drug use before admission to juvenile detention centers (JDC) in Peru and determine individual, family and social influences on behavior. Methods A cross-sectional analysis was performed using data from the 2016 National Population Census in Juvenile Detention Centers (NPCJDC). A total of 1960 Peruvian adolescent offenders were included. Generalized linear models of the Poisson family with a log link function were used to determine if characteristics before admission to a JDC were associated with drug use. These characteristics included employment, depression, neighborhood gang activity, having friends with a criminal record, a history of multiple admissions to a JDC, a history of running away from home, physical abuse during childhood and family history of drug use and incarceration. Results More than half of young offenders reported using drugs before entering a JDC (59%) in Peru. The drug most frequently consumed was cannabis (86.6%), followed by cocaine and/or crack (11.6%), and inhalants and/or pills (1.8%). Smoking cigarettes [prevalence ratios (PR): 1.12, p = 0.003], using alcohol (PR: 1.22, p = 0.003), neighborhood gang activity (PR: 1.28, p < 0.001), having friends with a criminal record (PR: 1.62, p < 0.001), running away from home (PR: 1.20, p < 0.001) and a family history of incarceration (PR: 1.09, p = 0.010) were associated with drug use prior to admission to a JDC. Conclusion Drug use before admission to a JDC was high among young offenders in Peru, with marijuana being the drug most frequently used. Having friends with a criminal record and neighborhood gang activity had the greatest association with drug use in young offenders.

Background: There is considerable interest in the use of cannabinoids for symptom control in palliative care, but there is little high-quality evidence to guide clinical practice. Objectives: Assess the feasibility of using global symptom burden measures to assess response to medicinal cannabis, to determine median tolerated doses of cannabidiol (CBD) and tetrahydrocannabinol (THC), and to document adverse events (AEs). Design: Prospective two-arm open-label pilot trial of escalating doses of CBD and THC oil. Setting/Subjects: Participants had advanced cancer and cancer-related symptoms in a palliative and supportive care service in an Australian cancer center. Measurements: The main outcome measures were the number of participants screened and randomized over the time frame, the number of participants completing days 14 and 28 and providing total symptom distress scores (TSDSs) (measured using the Edmonton Symptom Assessment Scale), and the change from baseline of the TSDS at day 14. Results: Of the 21 participants enrolled (CBD, n = 16; THC, n = 5), 18 (86%) completed the primary outcome measure at day 14 and 8 completed at day 28. The median maximum tolerated doses were CBD, 300 mg/day (range 100-600 mg); THC, 10 mg/day (range 5-30 mg). Nine of 21 patients (43%) met the definition of response (≥6 point reduction in TSDS). Drowsiness was the most common AE. Conclusions: Trials of medicinal cannabis in advanced cancer patients undergoing palliative care are feasible. The doses of THC and CBD used in this study were generally well tolerated and the outcome measure of total symptom distress is promising as a measure of overall symptom benefit. Trial registration: ACTRN12618001205224.

Diffuse alveolar hemorrhage (DAH) is a clinical condition characterized by the rapid onset of dyspnea, hemoptysis and acute respiratory failure (ARF). It is commonly caused by autoimmune systemic vasculitis, pulmonary infections, drugs and tumors. Here, we report a case of DAH caused by frequent cannabis smoking. A 16-year old boy presented with hemoptysis, dyspnea and ARF soon after laparoscopic surgery for varicocele in general anesthesia. The suspected diagnosis of DAH emerged from the initial chest radiography, and it was then confirmed by CT scan findings and the bronchoalveolar lavage. His general conditions completely recovered after only 24 h of oxygen supplementation and after intravenous corticosteroid and antibiotic therapy. This is the first pediatric case of DAH related to smoking marijuana, even though the inhalational anesthetic agent sevoflurane might have also been involved in this pathogenesis. Other possible causes of DAH have been considered. Negative-pressure pulmonary edema could be ruled out because no clinical evidence of upper airway obstruction was observed during general anesthesia and throughout the surgery. In addition, a possible causative role of cannabis additives/contaminants could not be excluded. Given the high prevalence of cannabis smoking in young people and that DAH can be a complication in cannabis smokers, a careful history and high index of suspicion are recommended as part of the pre-operative assessment before these patients are proceeded to receive general anesthesia.

The associations between traumatic events, substance use and perceived discrimination have been rarely studied among migrants in host countries. We examined whether pre-migration potentially traumatic experiences (PTEs) or perceived discrimination (PD) are associated with substance use among migrants with voluntary (Russians) and forced (Kurds) migration backgrounds.Cross-sectional interview and health examination data from the Finnish Migrant Health and Wellbeing Study were used. The target sample (n = 1000 for each group) was drawn from the national population register using stratified random sampling by participants' country of birth and native language.Population-based data were collected from six cities in Finland during 2010-12.The participation rates were 68% (Russians) and 59% (Kurds). The analytical sample size varied (Russians n = 442-687, Kurds n = 459-613), as some participants completed only interview, health examination or short interview. The majority of Kurds had a refugee background (75%) while Russians had mainly migrated for other reasons (99%).The three main outcomes were self-reported binge drinking, daily smoking and life-time cannabis use. PTEs and PD were self-reported in the interview. Socio-demographic background, migration-related factors and current affective symptoms were adjusted for.Among Kurds, PTEs were associated with binge drinking [adjusted odds ratio (aOR) = 2.65, 95% confidence interval (CI) = 1.30-5.42] and PD was associated with life-time cannabis use (aOR = 3.89, 95% CI = 1.38-10.97) after adjusting for contextual factors. Among Russians, PTEs were associated with life-time cannabis use adjusting for contextual factors (aOR = 2.17, 95% CI = 1.12-4.18).In Finland, pre-migration traumatic experiences appear to be associated with life-time cannabis use among the Russian migrant population (voluntary migration) and binge drinking among the Kurdish migrant population (forced migration). Perceived discrimination in Finland appears to be associated with life-time cannabis use among Kurdish migrants.

To estimate trends in the prevalence of cannabis use and risk perceptions of cannabis use from 2005 to 2017 among United States people with and without depression.Linear time trends of the prevalence of any, daily and non-daily past 30-day cannabis use and perceived great risk associated with regular cannabis use (outcome variables) among people with and without past-year depression were assessed using logistic regression with survey year as the predictor. All analyses were adjusted for gender, age, race/ethnicity and income; models assessing time trends of cannabis use prevalence were also adjusted for perceived risk.The United States: National Survey on Drug Use and Health, an annual cross-sectional survey, 2005-17 public use data files.A total of 728 691 people aged ≥ 12 years.Self-report of any, daily and non-daily past 30-day cannabis use and perceived great risk associated with regular cannabis use.The prevalence of any, daily and non-daily cannabis use in the past month was higher among those with depression versus those without [e.g. 2017 for any use: 18.94 versus 8.67%; adjusted odds ratio (aOR) = 2.17 (95% confidence interval (CI) = 1.92, 2.45)]. Any, daily and non-daily cannabis use increased among people with and without depression from 2005 to 2017, yet the increase in any (aORs = 1.06 versus 1.05; P = 0.008) and daily (aORs = 1.10 versus 1.07; P = 0.021) cannabis use adjusted for socio-demographic characteristics was more rapid among those with depression. Perception of great risk associated with regular cannabis use was significantly lower among those with depression (P < 0.001) and decreased significantly more rapidly over the study period among people with depression, compared with those without (aORs = 0.89 versus 0.92; P < 0.001).The prevalence of cannabis use in the United States increased from 2005 to 2017 among people with and without depression and was approximately twice as common among those with depression. People with depression experienced a more rapid decrease in perception of risk, which may be related to the more rapid increase in any and daily past-month cannabis use in this group.

The objectives of this review were to understand the prevalence of cannabis use and how cannabis is associated with transition to psychosis, symptoms, cognition, trauma and family history in clinical high risk (CHR) for psychosis individuals.A systematic literature review was conducted to find studies that examined cannabis use in CHR individuals, with no limitations on the geographical area, and included publications up to November 2018. Studies were screened for inclusion based on detailed criteria, and data were extracted on cannabis use and associated outcomes. A quantitative synthesis by meta-analysis was performed where appropriate, otherwise, a qualitative synthesis was conducted.Overall, 36 studies met inclusion criteria with an average age of 20.1 years and 58.4% males. Prevalence of lifetime cannabis use was 48.7%, whereas current cannabis use was 25.8% and the prevalence of cannabis use disorder/abuse or dependence was 14.9% across the studies. All cannabis use results had statistically significant heterogeneity ranging from 75.7 to 92.8%. The most commonly reported association with cannabis use was transition to psychosis, although the pooled relative risk (RR) was not statistically significant (RR = 1.11, 95% confidence interval = 0.89-1.37). For all other outcomes including symptoms, cognition, trauma, and family history, the evidence was limited, and therefore, the results were synthesized qualitatively.Almost half of CHR individuals have ever used cannabis. However, cannabis use has not been thoroughly researched regarding frequency and dose of use, and how other factors, such as symptoms, are associated with cannabis in CHR individuals.

Globally, there is increasing usage and legalization of cannabis. In addition to its reported therapeutic effects, cannabis has several health risks which are not clearly defined. Erectile dysfunction (ED) is the most common male sexual disorder and there are plausible mechanisms linking cannabis use to ED. No attempt has been made to collate the literature on this topic. The aim of this review was to summarize the prevalence and risk of ED in cannabis users compared to controls. A systematic review of major databases from inception to January 1, 2019, without language restriction, was undertaken to identify studies investigating cannabis use and presence of ED. The analysis compared the prevalence of ED in cannabis users versus controls. Consequently, the odds ratio (OR) with 95% confidence intervals (CI) was calculated, applying a random-effect model. Five case-control studies were included with data from 3,395 healthy men, 1,035 using cannabis (smoking) and 2,360 nonusers. The overall prevalence of ED in cannabis users was 69.1% (95% CI: 38.0-89.1), whilst the correspondent figure in controls was 34.7% (95% CI: 20.3-52.7). The OR of ED in cannabis users was almost four times that of controls (OR = 3.83; 95% CI: 1.30-11.28; p = .02), even if characterized by high heterogeneity (I2 = 90%) and the prediction intervals overlapped 1.00 (95% CI: 0.35-7.26). Data suggest that ED is twice as high in cannabis users compared to controls. Future longitudinal research is needed to confirm/refute this and explore if a dose-response relationship between cannabis and ED may be evident.

Background andObjectives: Among HIV infection symptoms, sensory neuropathy (HIV-SN) remains a main cause of suffering, with incidence varying from 13-50%. So far, numerous pharmacological and non-pharmacological treatments have been tested, although few evidence-based analgesic options are available. We conducted an up-to-date systematic review and meta-analysis of the literature in order to evaluate the efficacy and safety of pharmacologic and non-pharmacologic treatments for pain control, in patients with HIV neuropathy. Materials and Methods: We searched MEDLINE, EMBASE, Scopus/Elsevier, The Cochrane Central Register of Controlled Trials (CENTRAL), USA Clinical Trials registry, and The International Web of Science up to April 2019. All randomized controlled trials evaluating efficacy and safety of non-pharmacologic and pharmacologic therapies were included. Efficacy was defined as pain reduction during the study period. Safety was estimated from adverse events. A meta-analysis was performed whenever possible. Results: 27 randomized controlled trials (RCTs) were included for analysis (7 evaluating non pharmacologic interventions, 20 pharmacologic therapies). Non-pharmacologic studies (n = 742) involved seven different therapeutic modalities. Only Acupuncture/Moxibustion showed pain reduction over placebo, Gracely Pain Scale Mean (SD): Acu/Moxa 0.85 (0.12), placebo 1.10 (0.09), p = 0.05. Pharmacologic studies, involving 2516 patients revealed efficacy for capsaicin 8% over placebo (mean difference -8.04 [95% CI: -14.92 -1.15], smoked cannabis (where pooling data for meta-analysis was not possible) and recombinant Nerve Growth Factor. Conclusion: Despite various modalities for pain control in HIV-SN, strongest evidence exists for capsaicin 8% and smoked cannabis, although of low methodological quality. Among non-pharmacologic modalities, only Acu/Moxa gave a marginal beneficial effect in one study, possibly limited by inherent methodological flaws.

As the purchase of cannabis becomes legalized in US states, cannabis marketing presents an unexplored regulatory landscape. Research examining other consumer products indicates marketing informs consumer product perceptions, use expectancies, and behavior. The current study examined how cannabis products are described on US cannabis retailer websites.We used the National Cannabis Industry Association website to identify 27 retailers, linked to brick-and-mortar locations in six states, who advertised cannabis flower products online, and thematically coded descriptions of each product sold (N=428).Cannabis strain product descriptions fell into six categories: psychoactive effects, physical effects, social effects, sensory profile, therapeutic and curative claims, and negatives/warnings. Relaxation/stress relief (47.4%) and happiness (43.9%) were the most commonly described psychoactive effects, and relaxation/sedation was the most common physical effect (41.6%). Many products noted sensory characteristics, such as fruity (38.1%) or sweet (31.3%) taste/smell. A significant number of retailers claimed that strains could relieve pain and depression. Reports of potential side effects or warnings were less common.Online cannabis retailers are making potentially unsubstantiated product claims. Future work should examine the potential for these claims to inform consumer behavior. Regulations should ensure that cannabis labeling does not mislead consumers or promote unsafe use.

The rapid emergence of novel psychoactive substances within the past decade has raised new concerns about the harms associated with unregulated drug use. Synthetic analogues-chemically related to established psychoactive substances like cannabis sativa and catha edulis-in particular have proliferated rapidly, allowing little opportunity for scientific research or the establishment of informal guidelines for safe use among consumers. To explore how synthetic substance use relates to other forms of use, this paper presents an analysis of polysubstance use among a sample of 676 people who use illicit substances in the United States. Participants were sampled from three greater metropolitan areas (Houston/Galveston, Texas; New York City; and New Orleans, Louisiana). Study researchers used cluster-type analyses to develop dendrogram visualizations of the interrelationships between substance types. Results suggest a considerable variation in substance and polysubstance use patterns across states in the U.S. Polysubstance use clustered around well-observed combinations like MDMA/cannabis and cocaine/heroin. Synthetic cannabinoids and cathinones showed no strong clustering with other substances. High rates of binge drinking among users of other substances further support the importance of interventions sensitive to the clinical challenges of polysubstance use.

Peripheral neuropathy can significantly impact the quality of life for those who are affected, as therapies from the current treatment algorithm often fail to deliver adequate symptom relief. There has, however, been an increasing body of evidence for the use of cannabinoids in the treatment of chronic, noncancer pain. The efficacy of a topically delivered cannabidiol (CBD) oil in the management of neuropathic pain was examined in this four-week, randomized and placebo-controlled trial.In total 29 patients with symptomatic peripheral neuropathy were recruited and enrolled. 15 patients were randomized to the CBD group with the treatment product containing 250 mg CBD/3 fl. oz, and 14 patients were randomized to the placebo group. After four weeks, the placebo group was allowed to crossover into the treatment group. The neuropathic pain scale (NPS) was administered biweekly to assess the mean change from baseline to the end of the treatment period.The study population included 62.1% males and 37.9% females with a mean age of 68 years. There was a statistically significant reduction in intense pain, sharp pain, cold and itchy sensations in the CBD group when compared to the placebo group. No adverse events were reported in this study.Our findings demonstrate that the transdermal application of CBD oil can achieve significant improvement in pain and other disturbing sensations in patients with peripheral neuropathy. The treatment product was well tolerated and may provide a more effective alternative compared to other current therapies in the treatment of peripheral neuropathy.

After many years of legal struggles for the legalisation of recreational use of cannabis, the Constitutional Court of South Africa ruled in favour of the applicants in September 2018. Although the ruling issued caution regarding the social challenges accompanying this legalisation, it did not address how the country would deal with the societal consequences of this ruling.The aim of this article was to discuss the social and public health implications of the legalisation of recreational cannabis on South Africa.Literature review on the social, health and legal impacts of legalisation of cannabis, considering experiences of other countries that have legalised cannabis.The legalisation brings a range of significant negative consequences, which include an expected increase in the number of users and the subsequent undesirable effects on the physical, mental and social health of communities.In terms of financial, infrastructural and human resources, South Africa cannot afford the consequences of the legalisation of recreational cannabis. Poor communities, children and the youth will carry the brunt of the scourge of cannabis use.

The Timeline Followback (TLFB) was originally developed to assess alcohol consumption patterns (American Journal of Public Health, 86, 1996, 966) and has been increasingly modified for Web-based use. Additionally, new modes of substance use administration have emerged, creating a need for an adaptable TLFB tool than can capture data such as cannabis product potency or prescription drug use. Our goal was to validate an online TLFB that reliably assesses a wide range of substances in greater detail.Using a within-subjects counterbalanced design, daily substance use data were collected from 50 college students over a 14-day retrospective period using both the traditional in-person TLFB and online TLFB (O-TLFB).All substance use variables, including detailed measures of cannabis metrics, correlated significantly (r's ranged from .653 to .944, p < .001) between TLFB versions. Further, results demonstrated that both the online TLFB and in-person TLFB demonstrated concurrent validity with both the Alcohol Use Disorders Identification Test (AUDIT) and Marijuana Dependence Scale (MDS).Overall, the data suggest that this new O-TLFB demonstrates strong reliability and delivers a versatile and secure tool for substance use assessment that is relevant to a variety of biomedical and psychological research contexts.

Cannabis, also known as marijuana, is one of the most commonly used substances for medical and recreational purposes globally. With the trend of global legalization of medical use of cannabis and even the recreational use, the prevalence of recreational use of cannabis has increased markedly over the past few years. Correspondingly, the potential health concerns related to cannabis consumption have also increased. Therefore, it is necessary for oral healthcare providers to understand the effects of cannabis use on oral health. This review briefly summarizes the components of cannabis, biologic activities on tissues, and mechanisms of action in human cells and tissues. Oral tissue expression of cannabinoid receptors and the potential association of cannabis to oral diseases are also examined. The goals of this review are to (1) elaborate the basic biology and physiology of cannabis in human oral tissues, and (2) provide a better understanding the effects of its use and abuse on oral health. Due to insufficient information, more well-designed studies should be conducted. It is urgent to include cannabis usage into dental patient health records.

Policy makers require evidence-based estimates of the economic costs of substance use-attributable lost productivity to set strategies aimed at reducing substance use-related harms. Building on a study by Rehm et al. (2006), we provide estimates of workplace costs using updated methods and data sources.We estimated substance use-attributable productivity losses due to premature mortality, long-term disability, and presenteeism/absenteeism in Canada between 2007 and 2014. Lost productivity was estimated using a hybrid prevalence and incidence approach. Substance use prevalence data were drawn from three national self-report surveys. Premature mortality data were from the Canadian Vital Statistics Death Database, and long-term disability and workplace interference data were from the Canadian Community Health Survey.In 2014, the total cost of lost productivity due to substance use was $15.7 billion, or approximately $440 per Canadian, an increase of 8% from 2007. Substances responsible for the greatest economic costs were alcohol (38% of per capita costs), tobacco (37%), opioids (12%), other central nervous system (CNS) depressants (4%), other CNS stimulants (3%), cannabis (2%), cocaine (2%), and finally other psychoactive substances (2%).In 2014, alcohol and tobacco represent three quarters of substance use-related lost productivity costs in Canada, followed by opioids. These costs provide a valuable baseline that can be used to assess the impact of future substance use policy, practice, and other interventions, especially important given Canada's opioid crisis and recent cannabis legalization.

The aim of the present study was to describe the profiles of a sample of young cannabis users not seeking care, for use in general practice in France.In this cross-sectional study, baseline data were used from a previous clinical randomized trial, in which a brief intervention was tested. The participants were 262 cannabis users aged 15 to 25 years who smoked at least one joint per month. Assessment was undertaken both by the GP and via an anonymous self-reporting questionnaire. All statistical analyses were performed using Stata software and R. We used multiple correspondence analysis to determine the profiles of users.Among the 262 patients, 46.2% were daily users (more than 30 joints per month), 25.6% were regular users (from 10 to 29 joints per month), and 28.2% were recent users (fewer than 10 joints per month). The higher the frequency of use, the greater the incidence of unaccompanied use, daily use and week use (p from <0.001 to 0.01). The motivations of daily users were mostly self-treatment and habit (p <0.05). The cannabis abuse screening trial score revealed risky use for 87.5% of daily users and 34.4% for recent users. Factorial analysis identified 5 profiles according to age, risk, and motive for use. The reasons for consultation were equally distributed among users regardless of their level of use or their profile (p > 0.05).The results provide support for the practice of asking young patients systematically about their cannabis use, allowing GPs to identify users who require medical care. GPs should consider the differences between participants according to their profile in order to determine the appropriate type of care.Clinicaltrials.gov NCT01433692.

This observational study examined the acute cognitive effects of cannabis. We hypothesized that cognitive performance would be negatively affected by acute cannabis intoxication. Twenty-two medical cannabis patients from Southwestern Ontario completed the study. The majority (n = 13) were male. Mean age was 36.0 years, and mean level of education was 13.7 years. Participants were administered the same brief neurocognitive battery three times during a six-hour period: at baseline ("Baseline"), once after they consumed a 20% THC cannabis product ("THC"), and once again several hours later ("Recovery"). The average self-reported level of cannabis intoxication prior to the second assessment (i.e., during THC) was 5.1 out of 10. Contrary to expectations, performance on neuropsychological tests remained stable or even improved during the acute intoxication stage (THC; d: .49-.65, medium effect), and continued to increase during Recovery (d: .45-.77, medium-large effect). Interestingly, the failure rate on performance validity indicators increased during THC. Contrary to our hypothesis, there was no psychometric evidence for a decline in cognitive ability following THC intoxication. There are several possible explanations for this finding but, in the absence of a control group, no definitive conclusion can be reached at this time.

Cannabinoids have been known as the primary component of cannabis for decades, but the characterization of the endocannabinoid system (ECS) in the 1990s opened the doors for cannabis' use in modern medicine. The 2 main receptors of this system, cannabinoid receptors 1 and 2, are found on cells of various tissues, with significant expression in the gastrointestinal (GI) tract. The characterization of the ECS also heralded the understanding of endocannabinoids, naturally occurring compounds synthesized in the human body. Via secondary signaling pathways acting on vagal nerves, nociceptors, and immune cells, cannabinoids have been shown to have both palliative and detrimental effects on the pathophysiology of GI disorders. Although research on the effects of both endogenous and exogenous cannabinoids has been slow due to the complicated legal history of cannabis, discoveries of cannabinoids' treatment potential have been found in various fields of medicine, including the GI world. Medical cannabis has since been offered as a treatment for a myriad of conditions and malignancies, including cancer, human immunodeficiency virus/acquired immunodeficiency syndrome, multiple sclerosis, chronic pain, nausea, posttraumatic stress disorder, amyotrophic lateral sclerosis, cachexia, glaucoma, and epilepsy. This article hopes to create an overview of current research on cannabinoids and the ECS, detail the potential advantages and pitfalls of their use in GI diseases, and explore possible future developments in this field.

Cannabis is known to have cardiovascular and psychoactive effectsThe association between active cannabis use disorder and postoperative outcomes remains unclear WHAT THIS MANUSCRIPT TELLS US THAT IS NEW: In the United States, administrative data demonstrate that cannabis use disorder has increased in prevalence from 2010 to 2015Active cannabis use disorder is not associated with a change in overall perioperative morbidity, mortality, length of stay, or costsHowever, active cannabis use disorder is associated with a meaningful increase in the risk of postoperative myocardial infarction BACKGROUND:: Although cannabis is known to have cardiovascular and psychoactive effects, the implications of its use before surgery are currently unknown. The objective of the present study was to determine whether patients with an active cannabis use disorder have an elevated risk of postoperative complications.The authors conducted a retrospective population-based cohort study of patients undergoing elective surgery in the United States using the Nationwide Inpatient Sample from 2006 to 2015. A sample of 4,186,622 inpatients 18 to 65 yr of age presenting for 1 of 11 elective surgeries including total knee replacement, total hip replacement, coronary artery bypass graft, caesarian section, cholecystectomy, colectomy, hysterectomy, breast surgery, hernia repair, laminectomy, and other spine surgeries was selected. The principal exposure was an active cannabis use disorder, as defined by International Classification of Diseases, Ninth Edition, Clinical Modification (ICD-9-CM) diagnostic codes for cannabis dependence and cannabis abuse. The primary outcome was a composite endpoint of in-hospital postoperative myocardial infarction, stroke, sepsis, deep vein thrombosis, pulmonary embolus, acute kidney injury requiring dialysis, respiratory failure, and in-hospital mortality. Secondary outcomes included hospital length of stay, total hospital costs, and the individual components of the composite endpoint.The propensity-score matched-pairs cohort consisted of 27,206 patients. There was no statistically significant difference between patients with (400 of 13,603; 2.9%) and without (415 of 13,603; 3.1%) a reported active cannabis use disorder with regard to the composite perioperative outcome (unadjusted odds ratio = 1.29; 95% CI, 1.17 to 1.42; P < 0.001; Adjusted odds ratio = 0.97; 95% CI, 0.84 to 1.11; P = 0.63). However, the adjusted odds of postoperative myocardial infarction was 1.88 (95% CI, 1.31 to 2.69; P < 0.001) times higher for patients with a reported active cannabis use disorder (89 of 13,603; 0.7%) compared with those without (46 of 13,603; 0.3%) an active cannabis use disorder (unadjusted odds ratio = 2.88; 95% CI, 2.34 to 3.55; P < 0.001).An active cannabis use disorder is associated with an increased perioperative risk of myocardial infarction.

Accumulated evidence indicates that cannabidiol (CBD), a nonpsychotomimetic and nonaddictive main component of the Cannabis sativa plant, reverses anxiety-like behavior. The purpose of the present study was to assess the efficacy of CBD treatment for Japanese late teenagers with social anxiety disorder (SAD). Thirty-seven 18-19-year-old Japanese teenagers with SAD and avoidant personality disorder received, in a double-blind study, cannabis oil (n = 17) containing 300 mg CBD or placebo (n = 20) daily for 4 weeks. SAD symptoms were measured at the beginning and end of the treatment period using the Fear of Negative Evaluation Questionnaire and the Liebowitz Social Anxiety Scale. CBD significantly decreased anxiety measured by both scales. The results indicate that CBD could be a useful option to treat social anxiety.

Cannabis use has become increasingly common in the U.S. in recent years, with legalization for medical and recreational purposes expanding to more states. With this increase in use and access, providers should be prepared to have more conversations with patients about use. This review provides an overview of cannabis terminology, pharmacology, benefits, harms, and risk mitigation strategies to help providers engage in these discussions with their patients. Current evidence for the medical use of cannabis, cannabis-related diagnoses including cannabis use disorder (CUD) and withdrawal syndromes, and the co-use of opioids and cannabis are discussed. It is crucial that providers have the tools and information they need to deliver consistent, evidence-based assessment, treatment, prevention and harm-reduction, and we offer practical guidance in these areas.

Hair is one of the key samples for judging drug abuse in the field of forensic science. However, few studies have examined synthetic cannabinoids and their metabolites in human hair. Synthetic cannabinoids are a class of chemicals that bind to cannabinoid receptors, but they differ structurally from the cannabinoids found in cannabis. They have been sold sprayed on dried, shredded plant material under brand names such as "Spice" since the 2000s. In South Korea, synthetic cannabinoids have been widely distributed since 2009 and many types detected up to now. Unlike traditional drugs such as methamphetamine and cannabis, the abuse trends of synthetic cannabinoids were variable by regions and changed according to the times. If new types of synthetic cannabinoids become popular which has been altered in some structures, it becomes difficult to identify using exist analytical method. Therefore, it is important to develop a new analytical method for synthetic cannabinoids currently being abused in society. In this study, we developed simultaneous analytical methods for the detection of 18 synthetic cannabinoids and 41 of their metabolites in authentic human hair samples using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Selectivity, linearity, limits of detection (LODs), limits of quantification (LOQs), precision, accuracy, matrix effect, recovery, and process efficiency were evaluated, and all results were acceptable. Additionally, the distribution of synthetic cannabinoids in the head hair of Korean drug abusers from 2016 to 2018 was investigated. Hair samples from 43 individuals suspected of synthetic cannabinoid use were provided by law enforcement agencies. The drugs detected most prevalently in the head hair of Korean drug abusers were AB-CHMINACA and JWH-210.

Hemp seeds and hempseed oil are marketed on- and off-line as health foods and cosmetics and have been reported to have high nutrient contents. However, because of the various side effects of cannabinoids, especially △9-tetrahydrocannabinol (THC), many countries regulate upper limits for THC in products, which creates the need for analytical techniques capable of measuring THC, cannabidiol (CBD), and cannabinol (CBN) levels in commercial hemp seeds and hempseed oil. In the present study, hemp seed and hempseed oil extracts obtained by methanol extraction, were analyzed by gas chromatography-mass spectrometry (GC/MS). Validation of the technique used was performed using calibration curves and by determining LODs, LOQs, specificities, selectivities, and intra- and inter-day precision and accuracies. In addition, matrix effects, process efficiencies, recoveries, and sample stabilities were investigated. In hemp seeds, as determined using the fully optimized method THC concentrations ranged from 0.06 to 5.91 μg/g, CBD concentrations from 0.32 to 25.55 μg/g, and CBN concentrations from 0.01 to 1.50 μg/g; CBN/THC ratios ranged from 0.1 to 1.60, and CBD/THC ratios from 0.11 to 62.56. Furthermore, the (THC + CBN)/CBD ratio of most hemp seed samples was less than one. In hempseed oil, THC concentrations ranged from 0.3 to 19.73 μg/mL, CBD concentrations from 6.66 to 63.40 μg/mL, CBN concentrations from 0.11 to 2.31 μg/mL, CBN/THC ratios from 0.12 to 0.42, and CBD/THC ratios from 3.21 to 22.50. Furthermore, (THC + CBN)/CBD ratios in all hempseed oil samples were less than one. The optimized methanol extraction-GC/MS technique was found to be satisfactory for determining THC, CBD, and CBN concentrations in hemp seeds and hempseed oil.

The burden of cannabis and other illicit drug use among youth represent a serious public health problem. The aim of the present study is to explore factors associated with cannabis and other illicit drug use among Nigerian secondary school adolescents of the six geopolitical zones of the country.A total sample of 4078 secondary school adolescents of 32 schools from the six geopolitical zones of Nigeria participated in a cross-sectional survey in December 2015-January 2016. The association of sociodemographic characteristics, parental smoking, parental permissiveness to drink, friends' marijuana or other drugs use, risk perceptions and beliefs with the risk of lifetime cannabis and other illicit drugs use was examined through multilevel logistic regression models.The mean age of the students involved in the study was 14.7 years. Older age, living in one-parent or family structures different from both parents household, parental smoking, parental permissiveness to drink alcohol, friends' use of marijuana or other drugs, low risk perception of harmful effects, and positive beliefs on marijuana or drugs use were associated with the risk of cannabis and illicit drugs use. The indicator of socioeconomic status was associated to the risk of using cannabis, but not to the risk of using illicit drugs.The present study highlights some correlates that influence the uptake of cannabis and drugs among Nigerian adolescents. Preventive programs addressing these factors could help to reduce the burden of the problem. Specific attention should be given to interventions to contrast the incorrect beliefs and perceptions.

Some studies suggest cannabis use negatively affects tobacco cessation outcomes, but findings have been mixed. We examined whether cannabis use was associated with tobacco cessation outcomes in a real-world primary care setting.The analytic dataset consisted of 35,246 patients who enrolled between 2014 and 2016 in a primary care-based smoking cessation program in Ontario, Canada. Past 30-day cannabis use, for recreational or medical purposes, was self-reported at enrollment. Thirty-day point prevalence tobacco smoking abstinence was self-reported via online or telephone survey at 6 months post-enrollment.Thirty days prior to enrollment, 79.9 % of patients had not used cannabis, 16.3 % used cannabis for recreational purposes only, and 3.8 % used cannabis for medical purposes. Unadjusted and adjusted odds of tobacco cessation at 6 months were reduced for patients using cannabis compared to non-users (ORs = 0.76-0.86, ps<0.05). When cannabis use was categorized by purpose, both unadjusted and adjusted odds of cessation were significantly lower for recreational users (ORs = 0.77-0.84, ps<0.05). Medical users had decreased odds of cessation in unadjusted analysis (OR = 0.74, 95 % CI = 0.61-0.89, p = 0.001), but not after adjustment for potential confounders. However, post-estimation contrasts did not indicate a significant difference between the effect of recreational and medical cannabis use.In a large real-world sample of patients seeking smoking cessation treatment, concurrent cannabis use was associated with decreased success with quitting smoking. Recreational cannabis use was consistently related to poorer cessation outcomes, but medical use was not. Additional research is needed to inform treatment strategies for this growing sub-population of smokers.

Little is known about the functional mechanisms through which genetic loci associated with substance use traits ascertain their effect. This study aims to identify and functionally annotate loci associated with substance use traits based on their role in genetic regulation of gene expression.We evaluated expression Quantitative Trait Loci (eQTLs) from 13 brain regions and whole blood of the Genotype-Tissue Expression (GTEx) database, and from whole blood of the Depression Genes and Networks (DGN) database. The role of single eQTLs was examined for six substance use traits: alcohol consumption (N = 537,349), cigarettes per day (CPD; N = 263,954), former vs. current smoker (N = 312,821), age of smoking initiation (N = 262,990), ever smoker (N = 632,802), and cocaine dependence (N = 4,769). Subsequently, we conducted a gene level analysis of gene expression on these substance use traits using S-PrediXcan.Using an FDR-adjusted p-value <0.05 we found 2,976 novel candidate genetic loci for substance use traits, and identified genes and tissues through which these loci potentially exert their effects. Using S-PrediXcan, we identified significantly associated genes for all substance traits.Annotating genes based on transcriptomic regulation improves the identification and functional characterization of candidate loci and genes for substance use traits.

Youth substance use prevention is a key public health priority. There is evidence that delaying substance use can improve health outcomes. While substance use is associated with negative outcomes at school, the benefits of delaying substance use on these outcomes are less well understood.The current study examined the substance use behaviours and school outcomes of 35,221 grade 12 students in Canada. Students were asked to report when they began using alcohol, cannabis, and tobacco products as well as school outcomes including school connectedness, math and English grades, truancy, and post-secondary aspirations and expectations. Regression models were used to examine the relationship between of age of initiation of alcohol, cannabis, and tobacco use and these outcomes.Students who abstained from substance use throughout high school had higher school connectedness, lower truancy, and higher grades in grade 12 than students who did not. Earlier cannabis use was associated with increased truancy in grade 12. English grades were higher among students who did not use tobacco. Finally, post-secondary educational aspirations and expectations were higher among students who initiated substance use later.Grade 12 school outcomes were the best among students who abstained from substance use throughout high school. However, among students who did engage in substance use, school connectedness, truancy, English grades, and educational aspirations and expectations were more favourable among those who initiated substance use at a later age.

The legalization of the production, sale, and possession of cannabis in Washington State in 2012 not only created the framework for a new legal industry, but also for a new regulated labor sector. In addition to typical occupational health and safety hazards associated with chemical and physical exposures, the transition from an illicit to a regulated workplace, the inconsistency between state and federal law, and the production of a unique psychoactive commodity crop that maintains value in the illicit marketplace creates a unique work environment with workplace concerns that are political, economic, and social in nature.We conducted a combination of semistructured key informant interviews targeted toward employers, focus groups that engaged employees, and an online survey with cannabis business owners and employees to identify concerns relating to worker health and safety.In addition to physical and chemical hazards related to their workplace, workers described health concerns that were a result of social, economic, and political forces facing the transitioning cannabis industry and resulting from an inconsistency between state and federal law. Important themes that emerged from these data included the legal and regulatory environment that the cannabis industry faces, cannabis as an agricultural good, crime, gender, cannabis consumption in the workplace, changing worker demographics, and emerging technologies in this rapidly evolving industry.The unique sociopolitical challenges for occupational health and safety that we identified among cannabis workers in Washington State are especially relevant as other states and nations follow the example of Washington State in legalizing the widespread commercial cultivation, sale, and use of cannabis. As other states and nations legalize, it will be important for employers, public health practitioners, and regulators to recognize how transitioning from an illicit to a legal marketplace impacts worker health. Further, understanding the challenges that result in transitioning a cannabis workforce may be extrapolated in the future to better understand how transitioning other goods and services from an unregulated to a regulated marketplace may impact worker health.

Acne severity and its response to treatment may be influenced by internal and external factors: the exposome.The aim of this international real-life survey was to assess the most involved exposome factors in acne.Eleven thousand individuals, aged between 15 and 39 years, with clinically confirmed acne or without acne, defined by age, gender and prevalence, were invited to participate in an Internet survey of 63 questions in order to assess the frequency of identified acne exposome factors.Data from 6679 questionnaires were used for statistical analysis purposes: 2826 from the acne group and 3853 from the control group. Nibbling, consumption of dairy products, sweets, alcohol or whey proteins, as well as exposure to pollution, stress, certain mechanical factors and humid or hot weather or sun exposure, were significantly (all P ≤ 0.05) more frequently reported for the acne group than for the control group. This was not the case for tobacco consumption. Data regarding the impact of cannabis consumption were insufficient for drawing any conclusions.Data from this international, anonymized Internet questionnaire conducted with more than almost 6700 participants add new arguments to assumptions made that certain exposome factors have an impact on acne. Nutrition, pollution, stress and harsh skincare, as well as climate and sun exposure may be considered the most frequent factors related to acne.

Medical cannabis use is an emerging topic of interest in orthopedics. Although there is a large amount of literature on medical cannabis use for managing various types of pain, few studies have focused on orthopedic conditions. There is little high-quality evidence in core orthopedic areas. The objective of this study was to summarize the literature on the efficacy of cannabis use for pain related to orthopedic conditions.We conducted a systematic review of the literature on the use of cannabinoids for pain management in core orthopedic conditions. Two independent reviewers extracted information on reporting quality, risk of bias, drugs, population, control, duration of study, pain outcomes and the authors’ conclusions regarding efficacy for pain outcomes.We identified 33 orthopedic studies, including 21 primary studies and 12 reviews. Study quality was generally low to moderate. Six of the included studies had a control group and 15 were noncontrolled studies. Methodologies, drugs and protocols of administration varied greatly across studies. Study conclusions were generally positive in noncontrolled studies and mixed in controlled studies. Studies using higher doses tended to conclude that cannabis use was effective, but the potential for harmful effects may also be increased with higher doses.Variability in the methodologies used in cannabis research makes it challenging to draw conclusions about dosing, routes and frequency of administration. Most of the existing evidence suggests that medical cannabis use is effective, but this efficacy has been demonstrated only when either there is no comparator or cannabis is compared with placebo. Studies using an active comparator have not demonstrated efficacy. Future research should focus on improving study reporting and methodologic quality so that protocols that optimize pain control while minimizing harmful effects can be determined.

Oilseed crop oils contain a variety of unsaturated fatty acids that are synthesized and regulated by fatty acid desaturases (FADs). In this study, 14 FAD3 (ω3 desaturase) protein sequences from oilseeds are analyzed and presented through the application of several computational tools. The results indicated a close relationship between Brassica napus and Camelina sativa, as well as between Salvia hispanica and Perilla frutescens FAD3s, due to a high similarity in codon preferences in codon usage clusters and the phylogenetic tree. The cis-acting element results reveal that the seed-specific promoter region of BnFAD3 contains the critical conserved boxes such as HSE and ABRE, which are involved in responsiveness to heat stress and abscisic acid. The presence of the aforementioned conserved boxes may increase cold acclimation as well as tolerance to drought and high salinity. Omega(ω)3 desaturases contain a Skn-1 motif which is a cis-acting regulatory element required involved in endosperm development. In oilseed FAD3s, leucine is the most repeated amino acid in FAD3 proteins. The study conveyed that B. napus, Camelina sativa, Linum usitatissimum, Vernicia fordii, Gossypium hirsutum, S. hispanica, Cannabis sativa, and P. frutescens have retention signal KXKXX/XKXX at their c-terminus sites, which is one of the most important characteristics of FADs. Additionally, it was found that BnFAD3 is a transmembrane protein that can convert ω6 to ω3 fatty acids and may simultaneously act as a potassium ion channel in the ER.

Introduction: Harmful alcohol and cannabis use are social concerns associated with a range of negative outcomes. Prior research has identified links between disrupted parent-child attachment and child-adolescent substance use. Materials and Methods: This study used cross-national data from the International Youth Development Study (IYDS; Victoria, Australia and Washington State, USA) to investigate the relationship between early adolescent family environment characteristics, mid-adolescent attachment to parents, and young adult harmful alcohol and cannabis use. The moderating role of state on these relationships was also tested. State-representative samples of students in Grade 7 (age 13, 2002) were recruited and followed longitudinally at ages 14, 15, and 25 (n = 1,945, 53% female, 50% in Victoria). Results: Cross-state differences were evident in levels of family management, parent attitudes favorable to drug use, sibling alcohol and cannabis use, attachment to parents, and past year alcohol and cannabis use. Significantly higher rates of problematic alcohol use were reported by young adults in Victoria (25% vs. 14% in Washington State). Young adults in Washington State reported significantly higher rates of problematic cannabis use (14% vs. 10% in Victoria). Path modeling showed that characteristics of positive family environments (e.g., low conflict) in early adolescence were associated with higher attachment to parents and lower alcohol and cannabis use in mid-adolescence. Sibling substance use and more favorable parent attitudes to drug use were associated with past year alcohol and cannabis use in mid-adolescence. Results showed higher attachment to parents in mid-adolescence did not uniquely predict lower problematic alcohol or cannabis use in young adulthood. No significant cross-state differences in this pattern of associations were found. Discussion: The implications of the current findings suggest that prevention and intervention strategies targeted at reducing problematic substance use into young adulthood may benefit from considering the influence of behavioral norms and attitudes in family relationships.

A high level of insight in first episode psychosis (FEP) is positively correlated to important prognostic factors such as medication adherence and functional outcome but is associated with increased depression level and suicidal behavior.This is the first study questioning the potential moderating role of cannabis use in the relationship between insight and depression one year after a FEP.In this prospective observational study, we enrolled 214 FEP patients who had provided informed consent and been referred to a specialized early psychosis program and followed for 36 months. A series of multivariate regression models were used. Baseline insight, medication adherence and cannabis use (level of use on a continuum) were entered as independent variables, while the PANSS (positive and negative), the MADRS and the SOFAS scores after one year were alternately selected as the dependent variable.We found a three-way interaction term between cannabis use, insight and medication adherence on depression level one year after the entry into the program. A high level of insight was significantly associated with higher MADRS scores in patients with high cannabis use, while depression decreased in high-insight patients with low cannabis use.Cannabis use continuation during the year following a first episode psychosis may play a significant role in the development or the maintenance of post-psychotic depression in patients who present with high level of insight and adherence to medication, stressing the need for specific therapeutic strategies in this subgroup of patients.

This study seeks to understand whether people substitute between recreational cannabis and conventional over-the-counter (OTC) sleep medications. UPC-level grocery store scanner data in a multivariable panel regression design were used to compare the change in the monthly market share of sleep aids with varying dispensary-based recreational cannabis access (existence, sales, and count) in Colorado counties between 12/2013 and 12/2014. We measured annually-differenced market shares for sleep aids as a portion of the overall OTC medication market, thus accounting for store-level demand shifts in OTC medication markets and seasonality, and used the monthly changes in stores' sleep aid market share to control for short-term trends. Relative to the overall OTC medication market, sleep aid market shares were growing prior to recreational cannabis availability. The trend reverses (a 236% decrease) with dispensary entry (-0.33 percentage points, 95% CI -0.43 to -0.24, p < 0.01) from a mean market share growth of 0.14 ± 0.97. The magnitude of the market share decline increases as more dispensaries enter a county and with higher county-level cannabis sales. The negative associations are driven by diphenhydramine- and doxylamine-based sleep aids rather than herbal sleep aids and melatonin. These findings support survey evidence that many individuals use cannabis to treat insomnia, although sleep disturbances are not a specific qualifying condition under any U.S. state-level medical cannabis law. Investigations designed to measure the relative effectiveness and side effect profiles of conventional OTC sleep aids and cannabis-based products are urgently needed to improve treatment of sleep disturbances while minimizing potentially serious negative side effects.

The purpose of this study is to gain a greater understanding of cancer survivors' attitudes, perspectives, and concerns about medical cannabinoids (MCs) for cancer symptom and side effect management. Using qualitative methods, we conducted four focus groups (n = 19) with cancer survivors recruited from a community-based cancer wellness center. Groups were audio-recorded and facilitated by experienced co-moderators who directed discussion using a semi-structured interview guide. Transcripts were coded using principles from Grounded Theory. Analyses revealed the following ten themes and percentages of codes applied: 1) Attitudes & Beliefs (25.3%), 2) Access (17.1%), 3) Information (15.5%), 4) Concern (14%), 5) How MCs Helped (12.6%), 6) Comfort (4.3%), 7) Confusion (3.6%), 8) Trust/Distrust (3.1%), 9) Behaviors (2.3%), and 10) Support (2.2%). Participants reported that MCs offer potential benefits for symptom management and side effect relief, especially in reducing and managing pain. Despite the growing number of states that are legalizing MCs, significant barriers exist that make knowledge and adequate access a challenge for many.

Neurotrophin levels and oxidative stress markers such as ceruloplasmin and free thiols have been shown to contribute to pathophysiology in several psychiatric disorders.Our aim is to evaluate whether those markers are altered in cannabis dependence.Forty-five cannabis-dependent patients diagnosed according to the DSM-IV criteria and 45 healthy controls matched according to sex, age, BMI, and smoking status were enrolled. Brain-derived neurotrophic factor (BDNF), ceruloplasmin, lipid hydroperoxide, and total free thiols were measured in both groups. Those who had psychiatric comorbidities were excluded before sampling.We found significantly increased BDNF, ceruloplasmin, and lipid hydroperoxide, and decreased free thiol levels in patients with cannabis dependence. There is also a positive correlation between BDNF and lipid hydroperoxide (n = r = 0.472, p < 0.001) and a negative correlation between BDNF and total thiols (n = r = -0.412, p = 0.001).Increased BDNF might be a sign of impaired neuronal plasticity that is crucial for memory formation and adaptive response to drug addiction. Neuronal plasticity in the ventral tegmental area dopaminergic neurons was implied to play a role in substance addiction disorders, and these adaptations can be secondary to oxidative stress. Our findings, including increased lipid hydroperoxide, ceruloplasmin, and decreased free thiols, might support this hypothesis. In conclusion, cannabis dependency alters BDNF levels and increases oxidative stress.

Across numerous studies, individuals with substance use disorders (SUDs) differed from non-using controls regarding valuation of delayed gratification and feedback processing. However, it remains unclear whether the magnitude of the effect sizes is different across these two cognitive processes and how specific SUDs as well as demographic and clinical moderators influence these effects. In this study we thus performed multilevel linear mixed-effects meta-analyses and meta-regressions to examine the effects of SUDs on the Delay Discounting Task (DD) and on the Iowa Gambling Task (IGT). We found a moderate to large effect for SUD on both, the IGT and DD. While the effect on the DD was generalized to all substance classes, a smaller effect for cannabis-related disorder when compared to other SUDs was found with regard to the IGT. Early onset of substance use and psychiatric comorbidities were associated with stronger effects on the DD. Our findings suggest that feedback processing is more vulnerable to specific substance effects, while valuation of delayed gratification depends more on developmental and clinical factors.

The effects of in utero exposure to illicit drugs on adult offspring are a significant and widespread but understudied global health concern, particularly in light of the growing opioid epidemic and emerging therapeutic uses for cannabis, ketamine, and MDMA. Epigenetic mechanisms including DNA methylation, histone modifications, and expression of non-coding RNAs provide a mechanistic link between the prenatal environment and health consequences years beyond the original exposure, and shifts in the epigenome present in early life or adolescence can lead to disease states only appearing during adulthood. The current review summarizes the literature assessing effects of perinatal illicit drug exposure on adult disease phenotypes as mediated by perturbations of the epigenome. Both behavioral and somatic phenotypes are included and studies reporting clinical data in adult offspring, epigenetic readouts in offspring of any age, or both phenotypic and epigenetic measures are prioritized. Studies of licit substances of abuse (i.e. alcohol, nicotine) are excluded with a focus on cannabis, psychostimulants, opioids, and psychedelics; current issues in the field and areas of interest for further investigation are also discussed.

In Italy, medical grade cannabis (MGC) can be prescribed for different medical conditions, including drug-resistant epilepsy (DRE), once standard and approved therapies have failed, or caused non-tolerable side effects. Here, we present a retrospective case series report of five patients with DRE who started therapy with MGC. Authorized ISO 9001:2008 pharmacies prepared MGC according to Italian laws. Olive oil extracts (OOEs) were prepared following standard extraction protocols, and cannabinoids were measured on each OOE to check for successful extraction.After treatment with MGC, all patients reported a reduction in seizure frequency and severity, and some reported improved mood, sleep quality, and general well-being without relevant side effects. Despite the small sample size and open-label nature of the data, we show that MGC may be successfully used to treat DRE. This is especially true when considering that no valid therapeutic option exists for these patients and that MGC was extremely well tolerated.

Cannabis has been cultivated as a source of food, fiber, and medicine globally, so the classification of Cannabis cultivars based on their chemical fingerprints is important to standardize and control the quality of Cannabis, ensure that patients receive a full and consistent spectrum of therapeutic benefits, and promote the further implementation of Cannabis-based products in clinical uses. In this study, a high-throughput analytical method, thermal desorption direct analysis in real time mass spectrometry (TD-DART-MS), was employed to classify various Cannabis hemp cultivars with multivariate analysis. Cannabis plant materials from four cultivars were analyzed directly by TD-DART-MS without solvent extraction. The total run time was 15 min including 8 min for data acquisition and 7 min for cooling down the thermal stage. Data preprocessing strategy such as data transformation was evaluated on the TD-DART-MS data set and cubic root transform has shown significant improvement to the classification. TD-DART-MS data was then processed by principal component analysis (PCA) and the results were compared with those from liquid chromatography-mass spectrometry (LC-MS) data. The samples were clustered based on cultivars by PCA, and the validation samples collected 2 months later were also grouped together with the original samples by cultivars after mean-centering the data sets. Partial least squares discriminant analysis (PLS-DA) models were constructed with the TD-DART-MS data sets and a 99.3 ± 0.3% classification accuracy was obtained from 100 independent bootstrapped Latin partition evaluations. Our results indicate that TD-DART-MS may be used as a screening tool for the classification of Cannabis cultivars. Graphical abstract.

Cannabis sativa L. is a plant long used for its textile fibers, seed oil, and oleoresin with medicinal and psychoactive properties. It is the main source of phytocannabinoids, with over 100 compounds detected so far. In recent years, a lot of attention has been given to the main phytochemicals present in Cannabis sativa L., namely, cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC). Compared to THC, CBD has non-psychoactive effects, an advantage for clinical applications of anti-tumor benefits. The review is designed to provide an update regarding the multi-target effects of CBD in different types of cancer. The main focus is on the latest in vitro and in vivo studies that present data regarding the anti-proliferative, pro-apoptotic, cytotoxic, anti-invasive, anti-antiangiogenic, anti-inflammatory, and immunomodulatory properties of CBD together with their mechanisms of action. The latest clinical evidence of the anticancer effects of CBD is also outlined. Moreover, the main aspects of the pharmacological and toxicological profiles are given.

The endocannabinoid and dopaminergic systems have independently been implicated in substance use disorder and obesity. We investigated a potential interaction between genetically inherited variation in fatty acid amide hydrolase (FAAH, C385A), which metabolizes the cannabis-like endocannabinoid anandamide, and dopaminergic system, measured by dopamine receptor levels and mRNA. Binding of the dopamine D3 preferring probe [C-11]-(+)-PHNO was measured with positron emission tomography (PET) in 79 human subjects genotyped for the FAAH C385A polymorphism (36/79 AC + AA). Autoradiography with [H-3]-(+)-PHNO and in situ hybridization with a D3-specific S-35 riboprobe were carried out in 30 knock-in mice with the FAAH C385A polymorphism (20/30 AC + AA). We found that the FAAH genetic variant C385A was associated with significantly higher (+)-PHNO binding in both humans and in knock-in mice, and this effect was restricted to D3 selective brain regions (limbic striatum, globus pallidus, and ventral pallidum (9-14%; p < 0.04) in humans and Islands of Calleja (28%; p = 0.036) in mice). In situ hybridization with a D3-specific S-35 riboprobe in FAAH knock-in C385A mice confirmed significantly increased D3 receptor mRNA across examined regions (7-44%; p < 0.02). The association of reduced FAAH function with higher dopamine D3 receptors in human and mouse brain provide a mechanistic link between two brain systems that have been implicated in addiction-risk. This may explain the greater vulnerability for addiction and obesity in individuals with C385A genetic variant and by extension, suggest that a D3 antagonism strategy in substance use disorders should consider FAAH C385A polymorphism.

Marijuana use is common and growing in the United States amid a trend toward legalization. Exposure to tobacco smoke is a well-described preventable cause of many cancers; the association of marijuana use with the development of cancer is not clear.To assess the association of marijuana use with cancer development.A search of PubMed, Embase, PsycINFO, MEDLINE, and the Cochrane Library was conducted on June 11, 2018, and updated on April 30, 2019. A systematic review and meta-analysis of studies published from January 1, 1973, to April 30, 2019, and references of included studies were performed, with data analyzed from January 2 through October 4, 2019.English-language studies involving adult marijuana users and reporting cancer development. The search strategy contained the following 2 concepts linked together with the AND operator: marijuana OR marihuana OR tetrahydrocannabinol OR cannabinoid OR cannabis; AND cancer OR malignancy OR carcinoma OR tumor OR neoplasm.Two reviewers independently reviewed titles, abstracts, and full-text articles; 3 reviewers independently assessed study characteristics and graded evidence strength by consensus.Rates of cancer in marijuana users, with ever use defined as at least 1 joint-year exposure (equivalent to 1 joint per day for 1 year), compared with nonusers. Meta-analysis was conducted if there were at least 2 studies of the same design addressing the same cancer without high risk of bias when heterogeneity was low to moderate for the following 4 cancers: lung, head and neck squamous cell carcinoma, oral squamous cell carcinoma, and testicular germ cell tumor (TGCT), with comparisons expressed as odds ratios (ORs) with 95% CIs.Twenty-five English-language studies (19 case-control, 5 cohort, and 1 cross-sectional) were included; few studies (n = 2) were at low risk of bias. In pooled analysis of case-control studies, ever use of marijuana was not associated with head and neck squamous cell carcinoma or oral cancer. In pooled analysis of 3 case-control studies, more than 10 years of marijuana use (joint-years not reported) was associated with TGCT (OR, 1.36; 95% CI, 1.03-1.81; P = .03; I2 = 0%) and nonseminoma TGCT (OR, 1.85; 95% CI, 1.10-3.11; P = .04; I2 = 0%). Evaluations of ever use generally found no association with cancers, but exposure levels were low and poorly defined. Findings for lung cancer were mixed, confounded by few marijuana-only smokers, poor exposure assessment, and inadequate adjustment; meta-analysis was not performed for several outcomes.Low-strength evidence suggests that smoking marijuana is associated with developing TGCT; its association with other cancers and the consequences of higher levels of use are unclear. Long-term studies in marijuana-only smokers would improve understanding of marijuana's association with lung, oral, and other cancers.PROSPERO identifier: CRD42018102457.

Multiple Sclerosis (MS) is a chronic autoimmune disease with no curative treatment available. While recent years have ushered in many effective new disease-modifying therapies for MS, they have not obviated the need for symptomatic treatments for MS-related pain. In this review, we discuss available approaches to control pain, which is one of the most common complaints MS patients have.The most recent research in this topic is directed towards non-pharmacologic interventions including water exercises, yoga and cannabis. More trials are being conducted on neuromodulation for MS-related neuropathic pain, including transcutaneous electrical nerve stimulation (TENS) and transcranial direct current stimulation (tDCS). Pain control for MS patients is challenging, considering the progressive and relapsing remitting nature of the disease, however, it is a very important aspect of it's management, as it improves mobility, exercise tolerance, concomitant depression and overall quality of life. Future research should focus on the use of neuromodulation in controlling MS pain.

Internet interventions have been developed and tested for several psychiatric and somatic conditions. Few people with substance use disorders receive treatment and many drug users say that they would prefer getting help from online tools. Internet interventions are effective for reducing alcohol and cannabis use. The aim of the current study is to understand differences between internet-based and face-to-face treatment of problematic substance use. The concept of alliance will be used as a theoretical frame for understanding differences between internet-based treatment and face-to-face treatment, as perceived by therapists.The study has a qualitative design and is based on 3 focus group interviews with 12 therapists working with internet-based treatment for alcohol or cannabis use problems within five different programs.The analysis revealed five themes in the differences between internet-based and face-to-face treatment: communication, anonymity, time, presence and focus. Treatment online in written and asynchronous form creates something qualitatively different from regular face-to-face meetings between patients and therapists. The written form changes the concept of time in treatment, that is, how time can be used and how it affects the therapist's presence. The asynchronous (i.e. time delayed) form of communication and the lack of facial expressions and body language require special skills.There are important differences between internet-based treatment and face-to-face treatment. Different aspects of the alliance seem to be important in internet-based treatment compared to face-to-face.

"Stealthing" is a form of sexual violence wherein a sexual partner purposefully removes a condom during penetration without the receptive partner's knowledge. Given the role of substance use in sexual violence broadly, we examined demographic and substance use correlates of stealthing perpetration (SP) and victimization (SV) among emerging adults. Participants comprised 2,550 18- to 25-year-olds (M age = 20.8, SD = 2.3), recruited via social media (48% female; 53.9% non-Hispanic White; 46.0% had another racial/ethnic identity; 67.4% heterosexual; 85.3% had some college education). Unadjusted analyses (t tests, χ2 analysis) and adjusted logistic regression analyses examined associations between demographics (age, education, race/ethnicity, sexual orientation) and substance use (binge drinking, marijuana use, other illegal drug use, and prescription drug misuse) with male SP and male and female SV. Five percent of males and 18.9% of females reported SV; 6.1% of males reported SP. In adjusted analyses, significant correlates of SP were: non-Hispanic White race/ethnicity (odds ratio [OR] = 0.39), binge drinking (OR = 1.39), cannabis use (OR = 1.37), and other drug use (OR = 1.43). Significant correlates of male SV were: non-Hispanic White race/ethnicity (OR = 0.28), non-heterosexual orientation (OR = 0.24), binge drinking (OR = 1.49), and other illegal drug use (OR = 1.79). Significant correlates of female SV were: older age (OR = 1.13), non-Hispanic White race/ethnicity (OR = 0.57), binge drinking (OR = 1.28), cannabis use (OR = 1.29), and other drug use (OR = 1.22). Consistent with literature linking alcohol to sexual violence, binge drinking correlated with both SV and SP, with other substance use also playing a role. Data are needed to explore these relationships using longitudinal, event-level assessments to investigate the influence of acute intoxication. Interventions to reduce sexually transmitted infections, unintended pregnancy, and sexual assault should include content on stealthing and substance use.

With the licensing of cannabidiol for drug resistant seizures in Dravet and Lennox Gastaut syndromes in the United states in 2018, interest in the potential for cannabis-based-medicinal products to meet currently unmet needs for people with epilepsy continues to grow. This review summarizes current knowledge and discusses the implications for future research and practice. Both cannabidiol and tetrahydrocannabinol, the main components, have been extensively studied in animal models, with multimodal mechanisms of action proposed. Only pure cannabidiol formulations have been rigorously evaluated in controlled trials thus far, with modest but significant improvements in motor seizures. Adverse effects include diarrhoea, somnolence and reduced appetite, with mostly acceptable tolerability, but a not insignificant (up to 1 in 23) risk of serious adverse events. Recognized drug interactions include with valproate (increased risk of hepatotoxicity) and clobazam (contributing to somnolence, increased secretions, probably chest infections, and potentially efficacy). Whilst there is public (and producer) interest in products also containing tetrahydrocannabinol, clinicians have justifiable concerns about exposing a group already vulnerable to mental health and neurobehavioural comorbidities to the associated additional risks in these domains. Artisanal preparations, with often inconsistent/unknown constituents are frequently used but not recommended. A gulf exists between the actual evidence, including a lack of comparative studies and public beliefs, fuelled by media and anecdote. Continued education of the public, policymakers, researchers and healthcare providers about what is and isn't yet known, together with on-going good quality research is essential to mitigate against future potential risks, particularly in relation to vulnerable populations. This article is part of the special issue entitled 'New Epilepsy Therapies for the 21st Century - From Antiseizure Drugs to Prevention, Modification and Cure of Epilepsy'.

In Europe, more than 50 approved cultivars of fiber hemp (Cannabis sativa L.) are in agricultural production. Their content of psychoactive tetrahydrocannabinol (THC) is legally restricted to <0.2% (%w/w in the dry, mature inflorescences). Cannabis strains with much higher THC contents are also grown, illegally or under license for drug production. Differentiation between these two groups relies on biochemical quantification of cannabinoid contents in mature floral material. For nonflowering material or tissue devoid of cannabinoids, the genetic prediction of the chemical phenotype (chemotype) provides a suitable method of distinction. Three discrete chemotypes, depending on the ratio of THC and the noneuphoric cannabidiol (CBD), can be distinguished: a "THC-predominant" type, a "CBD-predominant" type, and an intermediate chemotype. We present a systematic genetic prediction of chemotypes of 62 agricultural hemp cultivars grown in Europe. The survey reveals the presence of up to 35% BT allele-carrying individuals (representing either a THC-predominant or an intermediate chemotype) in some cultivars-which is unexpected considering the legal THC limit of 0.2% THC. The fact that 100% of the seized drug-type seeds in this study revealed at least one BT allele, reflects that plant breeding efforts have resulted in a fixation of the BT allele in recreational Cannabis. To guarantee a sincere forensic application based on a genetic chemotype prediction, we recommend not to classify material of unknown origin if the samples size is below nine genetically independent individuals.

Drug-resistant seizures are life-threatening and contribute to sustained hospitalization. We present the case of a critically ill 28-year-old male with Lennox-Gastaut syndrome who had approximately 30 seizures/day in the intensive care unit.Patient required mechanical ventilation and pharmacologically induced thiopentone coma. He was commenced on cannabidiol and subsequently extubated. He remained seizure-free thereafter on a combination of cannabidiol and anti-epileptic medication that predated his critical illness.Our case report provides a unique perspective on the role of cannabidiol in achieving remission from drug-resistant seizures in critically ill patients.

People who inject drugs (PWID) experience elevated rates of premature mortality. Although previous studies have demonstrated the role of supervised injection facilities (SIFs) in reducing various harms associated with injection drug use, including accidental overdose death, the possible impact of SIF use on all-cause mortality is unknown. Therefore, we examined the relationship between frequent SIF use and all-cause mortality among PWID in Vancouver, Canada.Data were derived from 2 prospective cohort studies of PWID in Vancouver, Canada, between December 2006 and June 2017. Every 6 months, participants completed questionnaires that elicited information regarding sociodemographic characteristics, substance use patterns, social-structural exposures, and use of health services including SIFs. These data were confidentially linked to the provincial vital statistics database to ascertain mortality rates and causes of death. We used multivariable extended Cox regression analyses to estimate the independent association between frequent (i.e., at least weekly) SIF use and all-cause mortality. Of 811 participants, 278 (34.3%) were women, and the median age was 39 years (IQR 33-46) at baseline. In total, 432 (53.3%) participants reported frequent SIF use at baseline, and 379 (46.7%) did not. At baseline, frequent SIF users were on average younger than nonfrequent users, and a higher proportion of frequent SIF users than nonfrequent users were unstably housed, resided in the Downtown Eastside neighbourhood, injected in public, had a recent non-fatal overdose, used prescription opioids at least daily, injected heroin at least daily, injected cocaine at least daily, and injected crystal methamphetamine at least daily. A lower proportion of frequent SIF users than nonfrequent users were HIV positive and enrolled in addiction treatment at baseline. The median duration of follow-up among study participants was 72 months (IQR 24-123). In total, 112 participants (13.8%) died during the study period, yielding a crude mortality rate of 22.7 (95% CI 18.7-27.4) deaths per 1,000 person-years. The median years of potential life lost per death was 34 (IQR 27-42) years. In a time-updated multivariable model, frequent SIF use was inversely associated with risk of all-cause mortality after adjusting for potential confounders, including age, sex, HIV seropositivity, unstable housing, at least daily cocaine injection, public injection, incarceration, enrolment in addiction treatment, and calendar year of interview (adjusted hazard ratio 0.46, 95% CI 0.26-0.80, p = 0.006). The main study limitations are the limited generalizability of findings due to non-random sampling, the potential for reporting biases due to reliance on some self-reported information, and the possibility that residual confounding influenced findings.We observed a high burden of premature mortality among a community-recruited cohort of PWID. Frequent SIF use was associated with a lower risk of death, independent of relevant confounders. These findings support efforts to enhance access to SIFs as a strategy to reduce mortality among PWID. Further analyses of individual-level data are needed to determine estimates of, and potential causal pathways underlying, associations between SIF use and specific causes of death.

Objectives: This article investigates distinct patterns of adverse childhood experiences (ACEs) in a representative sample of US older adults, and how the ACEs patterns relate to major depression and substance use disorder (SUD).Methods: Data came from the National Epidemiologic Survey on Alcohol and Related Conditions III. The study sample consisted of older adults aged 55 or older (N = 11,386). The dependent variable was past-year SUD measuring any DSM-5 diagnosis for alcohol, tobacco, cannabis, and other illicit drugs. The independent variables were the classes of ACEs identified using 11 types of early adversities. The mediating variable was past-year major depressive disorder. We conducted a latent class analysis (LCA) to identify latent classes of ACEs, estimated the relationships between the ACEs classes, major depressive disorder, and SUD, and tested mediation by major depression.Results: Results of the LCA identified four classes of ACEs: High Adversity (6%), Low Adversity (69%), Child Abuse (16%), and Parental Substance Use (8%). The three classes of High Adversity, Child Abuse, and Parental Substance Use showed significantly higher rates of SUD than the Low Adversity class. The High Adversity and Child Abuse classes were more likely to have major depression compared to the Low Adversity class. In addition, major depression mediated the association between ACEs and SUD for those two classes.Conclusion: The findings provide evidence for a long-term impact of ACEs on mental health and SUD later in life and emphasize trauma-informed care principles in interventions for older adults with SUD.

Opioid use, abuse, and associated mortality have reached an epidemic level. In some states, cannabis is being used to treat chronic pain. To examine the hypothesis that medical marijuana legislation may reduce adverse opioid-related outcomes if patients substitute cannabis for opioids for pain management, we conducted a clinical inquiry (Clin-IQ). We searched Ovid MEDLINE, Ovid MEDLINE In-Process, and Embase for studies using the search terms marijuana, cannabis, legal, marijuana smoking, medical marijuana, opioid-related disorders, cannabis use, medical cannabis, legal aspect, and opiate addiction. We included population-based articles published from January 1, 2012, through December 5, 2018, that assessed the relationship between marijuana use and decriminalization and the aforementioned opioid-related outcomes. Ten peer-reviewed studies met the inclusion criteria; 3 cross-sectional studies, 6 ecologic studies (ie, using aggregate data), and 1 retrospective cohort study. Eight studies reported associations between policies decriminalizing marijuana and reduced prescription opioid use, 1 study was inconclusive, and the retrospective cohort study reported an increase in adverse opioid-related outcomes. These results should be interpreted with caution given limitations associated with the studies' design. Results demonstrating association between marijuana decriminalization and opioid-related outcomes are mixed. Longitudinal studies are needed, and further analysis of this policy should continue to be tracked.

The basic sources of information on drug use are epidemiological surveys, although they have some limitations: their results may be conditioned by the lack of veracity of the responses and the sampling method makes it difficult to detect lowprevalence behaviours in target populations. This study aimed to establish the epidemiological pattern of drug use in the population undergoing drug testing in hair, in the framework of judicial investigations, in order to provide an additional approach to the knowledge of high-risk drug use.A cross-sectional study on drug use was conducted on the population subjected to drug testing in hair (N=5,292) in the forensic context. Prevalence of cannabis, cocaine, heroin, ketamine, amphetamine (AP), methamphetamine (MA), 3,4-methylenedioxy- methamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxy-N-ethylamphetamine (MDEA) and methadone uses were obtained. Association between drug use and demographics, and trends of prevalence over the period were analysed using the Pearson Chi-square test. Frequency distribution of drug concentrations in hair was obtained and it was assessed in relation to gender and age using the non-parametric Mann-Whitney U and Kruskal-Wallis H methods.During the period 2013-2015, prevalence of cocaine use was particularly high (49%), rating second among the population studied, after cannabis use (54%). Proportions of heroin, methadone, MDMA and amphetamine use ranged from 10% to 18%. There was a significant increase in prevalence of MDMA, heroin and amphetamine use during the period 2013-2015, as well as a significant decrease in methadone use. The rates of cannabis, cocaine and MDMA use were higher in men, whereas methadone use was higher among women.Cannabis and cocaine are the most frequently abused drugs among the population undergoing drug testing in hair in the framework of judicial investigations over the three-year period, although the proportions of heroin, MDMA and amphetamine users show an increasing trend. Drug use patterns vary according to age and sex, with a decrease in cannabis and MDMA use and an increase in heroin and methadone use as age increased; cannabis, cocaine and MDMA use are more prevalent among men and methadone use among women.

To report a case of accidental cannabidiol (CBD) oil overdose in a pediatric patient.CBD is one of over 100 pharmacologically active compounds in the marijuana plant (Cannabis sativa). Its absence of psychoactive effects and the abundance of anecdotal claims of effectiveness across a wide variety of conditions in both mainstream and social media have created an incredible amount of public interest in CBD oil in recent years. Such interest has led to increased consumer availability. Despite this increased access, such sales remain illegal at the federal level. While sales of CBD products not approved by the Food and Drug Administration continue to rise, purity, potency, labeling, and delivery devices remain inconsistent. This may lead to an increased risk of adverse events. The following report describes a case of accidental CBD overdose in a pediatric patient leading to a stay in the pediatric intensive care unit.The patient initially presented to the urgent care and was quickly transferred to the emergency department after being found unresponsive after administration of a dose of CBD oil earlier in the day. After arrival, his mental status and respiratory drive continued to deteriorate, and he was ultimately intubated. He was eventually extubated and transferred out of the pediatric intensive care unit after 48 hours and discharged after 72 hours. This patient was found to have a urine 9-carboxy-11-nor-Δ-9-tetrahydrocannabinol concentration of 123 ng/mL, suggestive of consumption of a substantial amount of tetrahydrocannabinol. However, samples from the same batch ingested by the patient were tested by both the manufacturer and U.S. Food and Drug Administration and contained only trace amounts of THC.As CBD oil use continues to rise, health care professionals should have an adequate understanding of current clinical evidence and state and federal legislation to counsel patients on CBD use in a practical and compassionate manner.

Some patients develop breakthrough psychotic symptoms on antipsychotic maintenance medication (BAMM), despite receiving therapeutic antipsychotic doses to which they previously responded.We examined the occurrence of BAMM in previously minimally treated first-episode patients with schizophrenia-spectrum disorders who were treated according to a standard protocol with a long-acting injectable antipsychotic and regularly assessed over 24 months.Of 99 patients (age = 24.1 ± 6.5 years, male = 73.7%) who received treatment for ≥6 months (mean follow-up = 20.0 ± 6.5 months) and had responded well to treatment, 21 (21.2%) developed BAMM using operationally defined criteria, after a mean of 17.4 ± 6.1 months. Baseline risk factors for BAMM included lower baseline Positive and Negative Syndrome Scale positive symptoms, poorer quality of life in social relationships and higher blood - high-density lipoprotein-cholesterol. Regarding intra-treatment-factors, BAMM was independently predicted by an increase in low-density lipoprotein-cholesterol and current cannabis use. We did not find a relationship between BAMM and cumulative antipsychotic exposure or dose escalation. While symptoms of the BAMM episode were less severe than during the first episode, the post-BAMM treatment response was poorer than that for the first psychotic episode, suggesting a relationship between BAMM and emergent treatment refractoriness.About one in five patients with first-episode schizophrenia developed BAMM during the first two years of treatment, despite assured antipsychotic LAI treatment, indicating that this phenomenon is not restricted to the chronic stages of illness. The role of cannabis use and a possible link between BAMM and blood lipids should be further explored.

Interstitial cystitis (IC) is a chronic bladder disorder with unclear etiology. The endocannabinoid system has been identified as a key regulator of immune function, with experimental evidence for the involvement of cannabinoid receptors in bladder inflammation. This study used intravital microscopy (IVM) and behavioral testing in lipopolysaccharide-induced IC, to investigate the anti-inflammatory analgesic effects of a natural dietary sesquiterpenoid, beta-caryophyllene (BCP), which is present in cannabis among other plants, and has reported agonist actions at the cannabinoid 2 receptor (CB2R). BCP's anti-inflammatory actions were compared to the synthetic CB2R-selective cannabinoid, HU308, and to an FDA-approved clinical treatment (dimethyl sulfoxide: DMSO). IVM data revealed that intravesical instillation of BCP and/or HU308 significantly reduces the number of adhering leukocytes in submucosal bladder venules and improves bladder capillary perfusion. The effects of BCP were found to be comparable to that of the selective CB2R synthetic cannabinoid, HU308, and superior to intravesical DMSO treatment. Oral treatment with BCP was also able to reduce bladder inflammation and significantly reduced mechanical allodynia in experimental IC. Based on our findings, we believe that CB2R activation may represent a viable therapeutic target for IC, and that drugs that activate CB2R, such as the generally regarded as safe (GRAS) dietary sesquiterpenoid, BCP, may serve as an adjunct and/or alternative treatment option for alleviating symptoms of inflammation and pain in the management of IC.

Marijuana use in pregnancy is common and self-report of use to healthcare providers is variable. This study evaluates the relationship between prior interaction with the justice system as well as other factors associated with self-report and continuation of use of marijuana in pregnancy.This retrospective cohort study included women with a positive urine toxicology test for marijuana at their initial prenatal visit. Prior interaction with the judicial system was determined by querying a publicly available database. Those who did and did not self-report use were compared using chi square and Fisher's exact test for analysis of categorical variables and t test for comparison of means. A logistic regression was performed to determine factors related to remaining positive at the time of birth.Of 597 women included in analysis, 308 (51.6%) self-reported use. African American women were more likely to self-report use (p = 0.02). Interaction with the justice system was not statistically predictive of self-report. Of 483 (80.9%) who had birth outcome data available, 117 (24.2%) had positive marijuana tests at the time of delivery. Women who tested positive at birth were older (27.3 v 25, p < 0.01), more likely to present later for care (p = 0.02) and more likely to have self-reported their use at their initial visit (p = 0.03).Discrepancies exist between pregnant women's self-report of marijuana use and biologic testing results. Women with positive toxicology testing who self-report use may do so due to more problematic use and may benefit from enhanced interventions.

To examine trends and contributing factors of opioid, heroin, and cannabis-associated emergency department (ED) visits in Nevada.The 2009 to 2017 Nevada State ED database (n = 7,950,554 ED visits) were used. Use of opioid, heroin, and cannabis, respectively, was identified by the International Classification of Diseases, 9th & 10th Revisions. Three multivariable models, one for each of the 3 dependent variables, were conducted. Independent variables included year, insurance status, race/ethnicity, use of other substance, and mental health conditions.The number of individuals with opioid, heroin, cannabis-associated ED visits increased 3%, 10%, and 23% annually from 2009 to 2015, particularly among 21 to 29 age group, females, and African Americans. Use of other substance (odds ratio [OR] = 3.91; 95% confidence interval [CI] = 3.84, 3.99; reference - no use of other substance), mental health conditions (OR = 2.48; 95% CI = 2.43, 2.53; reference - without mental health conditions), Medicaid (OR = 1.41; 95% CI = 1.38, 1.44; reference - non-Medicaid), Medicare (OR = 1.44; 95% CI = 1.39, 1.49; reference - non-Medicare) and uninsured patients (OR = 1.52; 95% CI = 1.49, 1.56; reference - insured) were predictors of all three substance-associated ED visits.With a steady increase in trends of opioid, heroin, and cannabis-associated ED visits in recent years, the main contributing factors include patient sociodemographic factors, mental health conditions, and use of other substances.

: Thanks to the success of modern antiretroviral therapy (ART), people living with HIV (PLWH) have life expectancies which approach that of persons in the general population. However, despite the ability of ART to suppress viral replication, PLWH have high levels of chronic systemic inflammation which drives the development of comorbidities such as cardiovascular disease, diabetes and non-AIDS associated malignancies. Historically, cannabis has played an important role in alleviating many symptoms experienced by persons with advanced HIV infection in the pre-ART era and continues to be used by many PLWH in the ART era, though for different reasons. Δ-Tetrahydrocannabinol (Δ-THC) and cannabidiol (CBD) are the phytocannabinoids, which have received most attention for their medicinal properties. Due to their ability to suppress lymphocyte proliferation and inflammatory cytokine production, there is interest in examining their therapeutic potential as immunomodulators. CB2 receptor activation has been shown in vitro to reduce CD4 T-cell infection by CXCR4-tropic HIV and to reduce HIV replication. Studies involving SIV-infected macaques have shown that Δ-THC can reduce morbidity and mortality and has favourable effects on gut mucosal immunity. Furthermore, ΔTHC administration was associated with reduced lymph node fibrosis and diminished levels of SIV proviral DNA in spleens of rhesus macaques compared with placebo-treated macaques. In humans, cannabis use does not induce a reduction in peripheral CD4 T-cell count or loss of HIV virological control in cross-sectional studies. Rather, cannabis use in ART-treated PLWH was associated with decreased levels of T-cell activation, inflammatory monocytes and pro-inflammatory cytokine secretion, all of which are related to HIV disease progression and comorbidities. Randomized clinical trials should provide further insights into the ability of cannabis and cannabinoid-based medicines to attenuate HIV-associated inflammation. In turn, these findings may provide a novel means to reduce morbidity and mortality in PLWH as adjunctive agents to ART.

Understanding a popular but still investigational medicinal plant.

Sexual minorities are disproportionately more likely than heterosexuals to suffer from substance use disorders, but relatively little is known about differences in substance use disorders across diverse sexual minority subgroups. There is also limited understanding of how different social stressors account for sexual orientation disparities in substance use disorders.Using nationally representative data collected in 2012-2013 (n=34,597), differences in past-year DSM-5 alcohol, cannabis, and tobacco use disorders were assessed across 4 sexual orientation groups (heterosexuals and 3 sexual minority subgroups, lesbian/gay-, bisexual-, and heterosexual-identified sexual minorities). This study assessed whether stressful life events mediated substance use disorder disparities between heterosexuals and each sexual minority subgroup, and whether stressful life events and lesbian, gay, and bisexual discrimination events mediated these substance use disorder differences. Analyses were conducted in 2019.For both men and women, substance use disorders and stress experiences varied by sexual identity. For example, compared with heterosexual men, larger proportions of gay and bisexual men had a past-year alcohol use disorder. Among women, all sexual minority subgroups had higher rates of each substance use disorder than heterosexuals. For each substance use disorder, stressful life events mediated disparities between heterosexuals and sexual minority subgroups, except for heterosexual-identified sexual minority men. Both stressful life events and lesbian, gay, and bisexual discrimination mediated substance use disorder differences between sexual minority subgroups, with stronger indirect effects through lesbian, gay, and bisexual discrimination for lesbians/gay men and stronger indirect effects through stressful life events for bisexual adults, generally.Sexual minority subgroups have a greater prevalence of substance use disorders, mediated through both stressful life events and lesbian, gay, and bisexual discrimination. More research is needed to comprehensively assess the processes underlying sexual orientation substance use disparities.

Using Canadian survey data, Callaghan and colleagues examined the distribution of cannabis quantities after converting reported quantities of different cannabis products into standard joint equivalents. We argue that the assumed amount of 0.5 g dried cannabis flowers unlikely represents a usual dose in average consumers. Moreover, some conversion factors are implausible with regard to the THC concentration levels in select products. As with standard drinks, standard joint equivalents should be consistent with potency, i.e. THC concentration, and should be lower than suggested by the authors.

The chemical composition of Cannabis sativa L. has been extensively investigated for several years; nevertheless, a detailed lipidome characterization is completely lacking in the literature. To achieve this goal, an extraction and enrichment procedure was developed for the characterization of phospholipids and sulfolipids. Firstly, a study on the solid-liquid extraction was performed, to maximize the recovery of the considered lipids; the best procedure consisted of a simple extraction with a mixture of methanol and chloroform (1:1, v/v). The hemp extracts were analyzed by ultra-high-performance liquid chromatography coupled to high-resolution mass spectrometry and lipids were tentatively identified by Lipostar. To improve the number of identifications, an enrichment method, based on graphitized carbon black solid phase extraction, was evaluated to fractionate phospholipids and sulfolipids into separate eluates. Recovery and matrix effects of the procedure were determined on a mixture of standard lipids, containing representative compounds for each considered lipid class. The optimized method allowed the tentative identification of 189 lipids, including 51 phospholipids and 80 sulfolipids, in the first and second fractions, respectively. The detection of only 6 sulfolipids in the first fraction and 9 phospholipids in the second fraction proved the efficacy of the fractionation method, which also allowed the number of lipid identifications to be increased compared to the same procedure without enrichment, which scored 100 lipids. Finally, a semi-quantitative analysis permitted the hemp polar lipidome to be characterized. The results of this study allow knowledge of the hemp chemical composition to be improved with a detailed description of its phospho- and sulfolipid profiles. Graphical abstract.

The legalization and regulation of currently illicit drugs has come to the forefront of drug policy debates in recent years, particularly in the context of cannabis legalization and the opioid crisis in North America. However, sufficient granularity on the various aspects of a legally regulated drug supply is missing from these debates. Further, the voices and opinions of people who use drugs have generally been absent from drug law reform deliberations. This study aimed to examine the views of people who use drugs and who are deeply impacted by drug policies to understand the perceived impacts and role of government under a legalized-regulated market.Four focus groups were held with people who use drugs in Sydney, Australia.Most participants supported various models of legalization, although the perspectives on these models were diverse. Overriding these views was skepticism over the government's role in regulating a legal market, as well as concern for the personal agency of people who use drugs under a medically regulated drug supply model. Some participants discussed potential harms (e.g. increases in use and initiation), but emphasized the benefits (e.g. increases in quality and safety) from legal reform.While there was support for legal models of drug supply regulation, findings have major implications in terms of how governments and medical systems may perpetuate the oppression of people who use drugs through regulation, and urge future drug policy deliberations to include broader perspectives from the affected community.

The use, misuse and co-use of alcohol, cannabis, tobacco, and other licit and illicit controlled substances has increased in past decades leading to higher rates of morbidity, overdose, and mortality in women of reproductive age. Co-use compounds the adverse health effects of substance use compared to single-use of similar substances. Little is known about the full range of substance combinations used by pregnant and non-pregnant women. We sought to describe patterns of co-use of alcohol, tobacco, and controlled substances, and examine correlates of co-use in a nationally-representative sample of women.Cross-sectional study using self-reported survey data from 2006 to 2014 for women ages 18-49 years (N = 160,371) in National Survey on Drug Use and Health data. We use weighted proportions and 95% confidence intervals (CI) to report differences in substance use patterns in pregnant and non-pregnant women. Multivariate logistic regression models assessed association between characteristics and type of substance use pattern.Prevalence of substance co-use among pregnant women is 5.1% and among non-pregnant women is 23.6%. Nearly all of the most frequent co-use patterns included alcohol, cannabis, or tobacco. Determinants of co-use among pregnant women included: younger age (18-25 years) compared to ≥ 26 years [AOR (95% CI): 1.81 (1.18, 2.80)]; and past year history of substance use [AOR 5.42 (3.59, 8.20)].Co-use of several substances, including and especially of tobacco, alcohol and cannabis, persists among pregnant women in the United States. Efforts that aim to improve maternal and child health should address the complexity of substance use during pregnancy, including and beyond opioids.

E-cigarettes are the most popular tobacco product among youth. As more states adopt cannabis legalization policies, youth cannabis use in e-cigarettes is a mounting concern.Data were from the 2016 and 2017 National Youth Tobacco Survey, a nationally-representative repeated cross-sectional survey administered to US middle and high school students. Ever use groups were categorized into e-cigarette ever users, cannabis in e-cigarette ever users, other tobacco ever users, and never users. Weighted multinomial logistic regression compared ever use groups, while controlling for state-level cannabis legalization and tobacco prevention polices, tobacco perceptions and exposures, and sociodemographic variables. Weighted prevalence of ever and current, or past 30 day, tobacco product use was determined by ever use groups.Compared to e-cigarette ever users, cannabis in e-cigarette ever users increased (Adjusted Relative Risk Ratio (ARRR) = 1.65; p < 0.01) from 2016 to 2017. Medical-only and medical and recreational cannabis laws, and no e-cigarette minimum legal sales age (MLSA) and increased e-cigarette MLSA at 19 or 21 were positively associated with cannabis in e-cigarette ever users (ARRR = 1.34-1.85; p < 0.01, each). Ever and current use of all individual tobacco products was highest among cannabis in e-cigarette ever users compared to e-cigarette and other tobacco ever users.Cannabis use in e-cigarettes has increased among youth, and these trends will likely continue as e-cigarettes continue to gain popularity and cannabis legalization policies proliferate. Targeted tobacco and cannabis prevention strategies are needed for youth, especially in states that have implemented cannabis 'medical and recreational laws.

Cocaine and/or cannabis use during pregnancy is a growing problem of relevance for global public health. Exposed children may have a wide range of perinatal complications, but there is little knowledge on their course.To describe and compare the health trajectories of children prenatally exposed and unexposed to cocaine and/or cannabis over 4 years.Retrospective, cohort study with a double control group. Exposed children were detected through a urine test by the Department of Neonatology of a public hospital between 2009 and 2013.A total of 29 exposed children and 58 unexposed children were assessed. The most common drugs detected in the exposed group were cocaine and cannabis. Most mothers were poly-drug users. The exposed group showed significant differences in relation to a lower frequency of health checkups (p < 0.0001) and a higher number of visits to the emergency department (p = 0.0295) and hospitalizations (p = 0.007), mainly due to respiratory conditions. In addition, they had a greater rate of chronic obstructive pulmonary disease, changes of home, and legal interventions. In this group, 1 child and 2 parents had a violent death. No deaths were reported in the unexposed group.Conclusions: Children prenatally exposed to cocaine and/or cannabis had a lower number of health checkups and a higher number of visits to the emergency department and hospitalizations. Besides, they showed a greater rate of chronic obstructive pulmonary disease, changes of home, legal interventions, and violent deaths in the direct family group.

Marijuana may be used by some patients with gastroparesis (Gp) for its potential antiemetic, orexigenic, and pain-relieving effects.The aim of this study was to describe the use of marijuana by patients for symptoms of Gp, assessing prevalence of use, patient characteristics, and patients' perceived benefit on their symptoms of Gp.Patients with symptoms of Gp underwent history and physical examination, gastric emptying scintigraphy, and questionnaires assessing symptoms. Patients were asked about the current use of medications and alternative medications including marijuana.Fifty-nine of 506 (11.7%) patients with symptoms of Gp reported current marijuana use, being similar among patients with delayed and normal gastric emptying and similar in idiopathic and diabetic patients. Patients using marijuana were younger, more often current tobacco smokers, less likely to be a college graduate, married or have income > $50,000. Patients using marijuana had higher nausea/vomiting subscore (2.7 vs 2.1; p = 0.002), higher upper abdominal pain subscore (3.5 vs 2.9; p = 0.003), more likely to be using promethazine (37 vs 25%; p = 0.05) and dronabinol (17 vs 3%; p < 0.0001). Of patients using marijuana, 51% had been using it for more than 2 years, 47% were using this once or more per day, and 81% of marijuana users rated their benefit from marijuana as better or much better.A subset of patients (12%) with symptoms of Gp use marijuana. Patients with severe nausea and abdominal pain were more likely to use marijuana and perceive it to be beneficial for their symptoms.ClinicalTrials.gov Identifier: NCT01696747.

Patients diagnosed with schizophrenia are at least three times more likely to develop a substance use disorder than controls. These patients are frequently prescribed benzodiacepines as a coadjuvant drug, which have a high potential for addiction. We performed a literature review aiming to gather evidence on various topics concerning the use of benzodiacepines in schizophrenia, with a focus on possible abuse: 1) Prevalence of prescripted and non-prescripted benzodiacepine use among patients, 2) Prevalence of abusers, 3) Effects of long-term benzodiacepine abuse in schizophrenia prognosis, 4) Possible management strategies for benzodiacepine abuse in this population. Our search revealed there is a high variability (up to 20%) in benzodiacepine abuse among patients, with cannabis and stimulants being more frequent, and no clear demographic traits have been identified among these patients. Patients with affective symptoms are more likely to abuse benzodiazepines. Its long-term effects on prognosis have been debated, with some papers hinting at a higher mortality rate. Tapering benzodiacepines has been associated with an improvement in some cognitive functions. Management strategies for potential abuse do not differ greatly for this population, and no specific pharmacological aid can be indicated, but an integral approach is proposed.

The study aims to investigate: (1) the prevalence of cannabis among epileptic patients seen at Mansoura University Hospital, (2) serum levels and gene expression of cytokines in epilepsy patients and the controls. and (3) the possibility that cannabis use affects the cytokine levels in epilepsy patients, triggering its future use in treatment. We recruited 440 epilepsy patients and 200 controls matched for age, gender, and ethnicity. Of the epileptic patients, 37.5% demonstrated lifetime cannabis use with a mean duration of 15 ± 73 years. Serum levels of interleukin IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, and tumor necrosis factor-α (TNF-α), were analyzed and gene expression analysis was conducted only for those cytokines that were different between groups in the serum analysis. The "Epilepsy-only" patients had significantly higher serum and mRNA levels of IL-1α, β, IL-2,6,8, and TNF-α compared to the controls and the "Cannabis+Epilepsy" group (p = 0.0001). IL-10 showed significantly lower levels in the "Epilepsy-only" patients compared to the controls and "Cannabis+Epilepsy" (p = 0.0001). Cannabis use is prevalent among epilepsy patients. Epilepsy is characterized by a pro-inflammatory state supported by high serum and gene expression levels. Cannabis users demonstrated significantly lower levels of inflammatory cytokines compared to epilepsy non-cannabis users which might contribute to its use in the treatment of resistant epilepsy.

Sexual minority adolescents are more likely to have mental health problems, adverse social environments, and negative health outcomes compared with their heterosexual counterparts. There is a paucity of up-to-date population-level estimates of the extent of risk across these domains in the UK. We analysed outcomes across mental health, social environment, and health-related domains in sexual minority adolescents compared with their heterosexual counterparts in a large, contemporary national cohort.The Millennium Cohort Study (MCS) is a birth cohort study in the UK following up children born between Sept 1, 2000, and Jan 11, 2002 across England, Wales, Scotland, and Northern Ireland. Children recruited from the MCS have been followed up over six recruitment sweeps to date at ages 9 months, 3 years, 5 years, 7 years, 11 years, and 14 years. We analysed mental health, social, and health-related outcomes in sexual minority versus heterosexual adolescents at age 14 years. Additionally, we estimated the accumulation of multiple adverse outcomes in both groups. The primary aim of the study was to assess whether sexual minority adolescents experienced more adverse outcomes than heterosexual adolescents.Between January, 2015, and April, 2016, 9885 adolescents provided a response about their sexual attraction. 629 (6%) of 9885 adolescents (481 female participants and 148 male participants) were identified as sexual minorities. 9256 (94%) of 9885 participants (4431 female and 4825 male) were attracted to the opposite sex or not attracted to the same sex and identified as heterosexual. Sexual minority adolescents were more likely to experience high depressive symptoms (odds ratio [OR] 5·43, 95% CI 4·32-6·83; p<0·0001), self-harm (5·80, 4·55-7·41; p<0·0001), lower life satisfaction (3·66, 2·92-4·58; p<0·0001), lower self-esteem (β 1·83, 95% CI 1·47-2·19; p<0·0001), and all forms of bullying and victimisation. Sexual minorities were more likely to have tried alcohol (OR 1·85, 95% CI 1·47-2·33; p<0·0001), smoking (2·41, 1·92 -3·03; p<0·0001), and cannabis (3·22, 2·24-4·61; p<0·0001), and also had increased odds of being less physically active (β 0·36, 95% CI 0·25-0·46; p<0·0001), perceiving themselves as overweight (OR 1·73, 95% CI 1·40-2·14; p<0·0001), and dieting to lose weight (1·98, 1·58-2·48; p<0·0001). Sexual minority adolescents had more co-occurring mental health outcomes (mean 1·43 of 3 outcomes, 95% CI 1·34-1·52) compared with heterosexual adolescents (0·40 of 3 outcomes, 0·38-0·41), and more total cumulative difficulties (mean 9·43 of 28 outcomes, 95% CI 9·09-9·76 in sexual minority adolescents vs 6·16 of 28 outcomes, 6·08-6·23 in heterosexual adolescents).Sexual minority adolescents in the UK experience disparities in mental health, social, and health-related outcomes despite living in a time of substantial progress in rights for sexual minorities. These adverse outcomes co-occur, with implications for lifelong health and social outcomes. Health and educational practitioners should be aware of the increased risk for adverse outcomes in sexual minority adolescents.None.

Attentional bias, the automatic selective attentional orientation towards drug-related stimuli is well demonstrated in substance users. However, attentional bias studies of cannabis users specifically have thus far been inconclusive. Thus, the aim of this systematic review and meta-analysis was to synthesize the currently available literature regarding cannabis related attentional bias in cannabis users.Literature search and selection was carried out, following the PRISMA guidelines, with all included studies investigating the relationship between cannabis use and attentional bias towards cannabis cues.Fourteen manuscripts, reporting on 1271 participants (cannabis users n = 1044; controls n = 217), were considered for the systematic-review and majority were included in a meta-analysis. Studies reviewed used three types of attentional bias tasks: pictorial stimuli, word stimuli, and non-cannabis stimuli tasks. Greater attentional bias towards cannabis pictures (d = 0.42, P < 0.0001) and words (d = 0.63, P = 0.03) as well as both types of stimuli overall (d = 0.53, P < 0.0001) was observed in cannabis users compared to controls, though there was evidence of significant heterogeneity for both word stimuli and overall meta-analysis. Bigger effect sizes were associated with shorter durations of exposure to cannabis stimuli suggesting mainly automatic orientating rather than controlled attention processing.These findings suggest that cannabis users display greater attentional bias towards cannabis cues, likely an automatic process, than control groups. Future studies employing shorter exposure durations may validate attentional bias as a treatment target for the development of interventions in people with cannabis use disorder.

It is unclear whether cannabis use causes cognitive decline; several studies show an association between cannabis use and cognitive decline, but quasi-experimental twin studies have found little support for a causal effect. Here, we evaluate the association of cannabis use with general cognitive ability and executive functions (EFs) while controlling for genetic and shared environmental confounds in a longitudinal twin study.We first examined the phenotypic associations between cannabis initiation, frequency, and use disorder with cognitive abilities, while also controlling for pre-use general cognitive ability and other substance involvement. We tested the concurrent association between the cannabis use variables and cognitive abilities in late adolescence and young adulthood and the longitudinal association between cannabis use variables during adolescence and young adulthood cognitive abilities. Next, we used multilevel models to test whether these relations reflect between- and/or within-twin pair associations.Phenotypically, cannabis use was related to poorer cognitive functioning, although most associations were negligible after accounting for other substance use. Nevertheless, there were few significant within-family twin-specific associations, except that age 17 cannabis frequency was associated with worse age 23 Common EF and general cognitive ability.We found little support for a potential causal effect of cannabis use on cognition, consistent with previous twin studies. Results suggest that cannabis use may not cause decline in cognitive ability among a normative sample of cannabis users.

Nitrogen (N) availability represents one of the most critical factors affecting cultivated crops. N is indeed a crucial macronutrient influencing major aspects, from plant development to productivity and final yield of lignocellulosic biomass, as well as content of bioactive molecules. N metabolism is fundamental as it is at the crossroad between primary and secondary metabolic pathways: Besides affecting the synthesis of fundamental macromolecules, such as nucleic acids and proteins, N is needed for other types of molecules intervening in the response to exogenous stresses, e.g. alkaloids and glucosinolates. By partaking in the synthesis of phenylalanine, N also directly impacts a central plant metabolic 'hub'-the phenylpropanoid pathway-from which important classes of molecules are formed, notably monolignols, flavonoids and other types of polyphenols. In this review, an updated analysis is provided on the impact that N has on the multipurpose crop hemp (Cannabis sativa L.) due to its renewed interest as a multipurpose crop able to satisfy the needs of a bioeconomy. The hemp stalk provides both woody and cellulosic fibers used in construction and for biocomposites; different organs (leaves/flowers/roots) are sources of added-value secondary metabolites, namely cannabinoids, terpenes, flavonoids, and lignanamides. We survey the available literature data on the impact of N in hemp and highlight the importance of studying those genes responding to both N nutrition and abiotic stresses. Available hemp transcriptomic datasets obtained on plants subjected to salt and drought are here analyzed using Gene Ontology (GO) categories related to N metabolism. The ultimate goal is to shed light on interesting candidate genes that can be further studied in hemp varieties growing under different N feeding conditions and showing high biomass yield and secondary metabolite production, even under salinity and drought.

This systematic review summarizes and critically appraises the existing literature on brief interventions (BIs) for cannabis use among emerging adults.Eligible BIs were operationalized as 1-2 sessions focused exclusively on cannabis use for samples with mean ages between 15 and 30. Outcomes related to cannabis use, other substance use, mental health, help-seeking, or functional status were included. Two independent reviewers screened a total of 3638 records, identifying 244 studies for full-text screening. In total, 32 BIs in 26 primary studies with 6318 participants were included.Participants were typically not seeking treatment and using cannabis at least once a month. Most interventions were motivational, single sessions, and delivered in person. Few discussed concurrent psychiatric conditions. Pooling results at 1-3 months post-intervention, BIs compared to passive control slightly reduced symptoms of cannabis use disorder (SMD -0.14 [95% CI -0.26 to -0.01]) and increased the odds of abstinence (OR 1.73 [95% CI 1.13-2.66]). Other outcome results often favored BIs but were not significant. Results of studies comparing types of BIs (k = 8) or BIs to longer interventions (k = 1) are discussed narratively. Quality assessment suggested low to very low-quality evidence.This review indicates that BIs targeting non-treatment seeking emerging adults result in significant reductions in symptoms of cannabis use disorder and an increased likelihood of cannabis abstinence, however evidence is of low quality.

The focus of the current investigation is to examine the temporal relationship of gambling onset and alcohol, tobacco, and cannabis initiation in adolescents and young adults (M age = 20.3 years) by examining the prevalence and pattern of onset for each substance and gambling pairing and the associated risk between gambling and each substance use. Data were drawn from the multiwave Missouri Family Study (n = 1,349) of African American (AA; n = 450) and White families (n = 317) enriched for risk for alcohol use disorder and includes those who were assessed for gambling behaviors and problems: AA (360 males, 390 females) and White (287 males, 312 females). Findings indicated racial differences in the overall prevalence of gambling behaviors and substance use as well as patterns of initiation-particularly within gambling/alcohol and gambling/tobacco for males. Survival models revealed some similarities as well as differences across race and gender groups in associations of gambling with initiation of substances, as well as substances with initiation of gambling. Alcohol use (AA males only) and cannabis use (AA males and White females) elevated the hazards of initiating gambling. In contrast, gambling significantly elevated the hazards of initiation alcohol across 3 of 4 groups and of cannabis use in AA males only. The results highlight some overlapping as well as distinct risk factors for both gambling and substance use initiation in this cohort enriched for vulnerability to alcohol use disorder (AUD). These findings have implications for integrating gambling prevention into existing substance use prevention and intervention efforts-particularly but not exclusively for young AA males. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Autism spectrum disorder (ASD) is a high cost neurodevelopmental condition; and there are currently no effective pharmacological treatments for its core symptoms. This has led some families and researchers to trial alternative remedies - including the non-intoxicating Cannabis sativa-derived compound cannabidivarin (CBDV). However, how CBDV affects the human brain is unknown. Previous (pre)clinical evidence suggests that CBDV may modulate brain excitatory-inhibitory systems, which are implicated in ASD. Hence, our main aim was to test, for the first time, if CBDV shifts glutamate and/or GABA metabolites - markers of the brain's primary excitatory and inhibitory system - in both the 'typical' and autistic brain. Our subsidiary aim was to determine whether, within ASD, brain responsivity to CBDV challenge is related to baseline biological phenotype. We tested this using a repeated-measures, double-blind, randomized-order, cross-over design. We used magnetic resonance spectroscopy (MRS) to compare glutamate (Glx = glutamate + glutamine) and GABA + (GABA + macromolecules) levels following placebo (baseline) and 600 mg CBDV in 34 healthy men with (n = 17) and without (n = 17) ASD. Data acquisition from regions previously reliably linked to ASD (dorsomedial prefrontal cortex, DMPFC; left basal ganglia, BG) commenced 2 h (peak plasma levels) after placebo/CBDV administration. Where CBDV significantly shifted metabolite levels, we examined the relationship of this change with baseline metabolite levels. Test sessions were at least 13 days apart to ensure CBDV wash-out. CBDV significantly increased Glx in the BG of both groups. However, this impact was not uniform across individuals. In the ASD group, and not in the typically developing controls, the 'shift' in Glx correlated negatively with baseline Glx concentration. In contrast, CBDV had no significant impact on Glx in the DMPFC, or on GABA+ in either voxel in either group. Our findings suggest that, as measured by MRS, CBDV modulates the glutamate-GABA system in the BG but not in frontal regions. Moreover, there is individual variation in response depending on baseline biochemistry. Future studies should examine the effect of CBDV on behaviour and if the response to an acute dose of CBDV could predict a potential clinical treatment response in ASD.

Background: In October 2018, Canada became the second country to legalize non-medical cannabis. However, medical cannabis has been legally available in Canada since 2001 and, in 2015, approximately 800,000 Canadians reported using cannabis for medical purposes. Mental health is a common reason reported for using medical cannabis. Objectives: The current study examined perceived mental health among four groups: (1) Non/ex-users; (2) Recent non-medical users; (3) Recent unauthorized medical users; and (4) Recent authorized medical users. Methods: A total of 867 Canadian cannabis users and nonusers aged 16 to 30 were recruited through an online consumer panel in 2017, one year before non-medical cannabis legalization. Logistic and multinomial regression models were fitted to examine differences among cannabis use status and mental health measures. All estimates represent weighted data. Results: Self-reported emotional and mental health problems were higher among unauthorized (83.9%) and authorized medical cannabis users (83.2%) compared to non-medical users and non/ex-users (44.5% and 39.5%, respectively). Medical users were more likely to report using cannabis to manage or improve mental health problems than non-medical users (p < .001). There were few differences between unauthorized and authorized medical users, and between non/ex-users and non-medical users. Conclusions: The findings highlight a discrepancy between the recommendation that individuals with some mental health problems should avoid cannabis and the widespread practice of using cannabis to manage mental health. Education and reduced stigma around using cannabis after legalization in Canada may help address users coming forwards regarding use of cannabis for mental health problems.

Population pharmacokinetic models of Δ9-tetrahydrocannabinol (THC) have been developed for THC plasma and blood concentration data. Often, only the metabolites of THC are measurable when blood samples are obtained. Therefore, we performed a population pharmacokinetic analysis of THC, 11-OH-THC and THCCOOH plasma concentration data from a Phase I clinical trial of THC smoking.Frequently obtained plasma THC, 11-OH-THC and THCCOOH concentration data were obtained over 168 h from 6 subjects who smoked low (15.8 mg) and high dose (33.8 mg) THC cigarettes on 2 occasions. Bayesian estimates of the THC pharmacokinetic model from each individual for each dose were fixed prior to the sequential pharmacokinetic analysis of the metabolites.A 3-compartment model of THC was developed that has a steady-state volume of distribution (VdSS ) of 3401 ± 788 L and a clearance of 0.72 ± 0.10 L/min. 11-OH-THC was characterized by 50 ± 6% of the THC being directly cleared to a 3-compartment model with a VdSS of 415.2 ± 4.3 L and clearance of 0.78 ± 0.05 L/min. The THCCOOH model shared the central compartment of the 11-OH-THC model with a VdSS of 29.1 ± 0.05 L and a clearance of 0.12 ± 0.02 L/min. First order kinetics were observed for THC and THCCOOH between the low and high doses, but a nonlinear pattern was observed for 11-OH-THC.We describe the pharmacokinetics of THC, 11-OH-THC and THCCOOH including inter- and intraindividual variability of the parameter estimates of the model.

Cannabis is the most consumed illicit drug worldwide. As more countries consider bills that would legalize adult use of cannabis, health care providers, including eye care professionals (ophthalmologists, optometrists), will need to recognize ocular effects of cannabis consumption in patients. There are only 20 studies on the eyelid effects of cannabis usage as a medical treatment or a recreational drug. These include ptosis induction, an "eyelid tremor" appearance and blepharospasm attenuation. Six articles describe how adequately dosed cannabis regimens could be promising medical treatments for blepharospasm induced by psychogenic factors. Fourteen articles report eyelid tremors in intoxicated drivers and ptosis as a secondary effect in cannabinoid animal experimental models. The exact mechanism of cannabinoids connecting cannabis to the eyelids is unclear. Further studies should be conducted to better understand the cannabinoid system in relation to the eyelid and eventually develop new, effective and safe therapeutic targets derived from cannabis.

Vaping is a growing concern in adolescents, and a growing proportion is using electronic devices to inhale cannabis oil. The short-term and long-term effects of cannabis oil inhalation are not well understood. We report on a case of severe acute lung injury secondary to inhalation of cannabis oil via a vape pen, and propose a new term that describes lung injury related to vaping.

While imaging studies have demonstrated volumetric differences in subcortical structures associated with dependence on various abused substances, findings to date have not been wholly consistent. Moreover, most studies have not compared brain morphology across those dependent on different substances of abuse to identify substance-specific and substance-general dependence effects. By pooling large multinational datasets from 33 imaging sites, this study examined subcortical surface morphology in 1628 nondependent controls and 2277 individuals with dependence on alcohol, nicotine, cocaine, methamphetamine, and/or cannabis. Subcortical structures were defined by FreeSurfer segmentation and converted to a mesh surface to extract two vertex-level metrics-the radial distance (RD) of the structure surface from a medial curve and the log of the Jacobian determinant (JD)-that, respectively, describe local thickness and surface area dilation/contraction. Mega-analyses were performed on measures of RD and JD to test for the main effect of substance dependence, controlling for age, sex, intracranial volume, and imaging site. Widespread differences between dependent users and nondependent controls were found across subcortical structures, driven primarily by users dependent on alcohol. Alcohol dependence was associated with localized lower RD and JD across most structures, with the strongest effects in the hippocampus, thalamus, putamen, and amygdala. Meanwhile, nicotine use was associated with greater RD and JD relative to nonsmokers in multiple regions, with the strongest effects in the bilateral hippocampus and right nucleus accumbens. By demonstrating subcortical morphological differences unique to alcohol and nicotine use, rather than dependence across all substances, results suggest substance-specific relationships with subcortical brain structures.

Use of psychoactive substances is a common finding in studies on first-episode psychosis (FEP), and this has prognostic implications. We know very little about psychoactive substance use (SU) among patients with FEP in the Eastern Cape province (EC) of South Africa (SA).The study seeks to determine SU prevalence and associated features among inpatients with non-affective FEP in an acute mental health unit (MHU) in Nelson Mandela Bay, EC.Researchers conducted a retrospective clinical file review of a 12-month admission cohort of patients with FEP, without a concurrent mood episode, to the Dora Nginza Hospital MHU. Information collected included SU history, psychiatric diagnoses, and demographics. Data were then subjected to statistical analysis.Researchers conducted a retrospective clinical file review of a 12-month admission cohort of patients with FEP, without a concurrent mood episode, to the Dora Nginza Hospital MHU. Information collected included SU history, psychiatric diagnoses and demographics. Data were then subjected to statistical analysis.A total of 117 patients (86 [73.5%] males; 31 [26.5%] females) aged 18-60 years (mean 29 years) met the inclusion criteria. After controlling for missing information, 95 of 117 (81.2%) patients had a history of active or previous SU, 82 of 90 (91.1%) were single and 61 of 92 (66.3%) were unemployed. A significant association was found between SU and unemployment (p < 0.001), as well as male sex (p < 0.001). The most common substances used were cannabis (59.8%), followed by alcohol (57.3%) and stimulants (46.4%).In keeping with national and international literature, the results of this study showed a high prevalence of substance use in South African patients with first-episode psychosis. The high prevalence of lifetime substance use in this cohort compared to previous studies in South Africa requires further investigation and highlights the urgent need for dual diagnosis services in the Eastern Cape province.

Rates of cannabis use among patients receiving methadone maintenance therapy are high, and cannabis use may be associated with outcomes of methadone maintenance therapy. We examined the effect of cannabis use on opioid use in patients receiving methadone maintenance therapy to test the hypothesis that cannabis use is associated with a reduction in opioid use.In this systematic review, we searched MEDLINE/PubMed, Embase, PsycINFO, CINAHL and ProQuest Dissertations and Theses Global from inception to July 12, 2018. We summarized the effects of cannabis use on opioid use during methadone maintenance therapy and treatment retention. We conducted meta-analyses using a random effects model.We included 23 studies in our review. We performed a meta-analysis of 6 studies, with a total number of participants of 3676, examining use of cannabis and opioids during methadone maintenance therapy. Owing to high heterogeneity, we described the studies qualitatively but provide the forest plots as supplemental material. The overall quality of evidence was very low, with a high risk of bias, owing to the nature of observational studies.We found no consensus among studies that cannabis use is associated with reduced opioid use or longer treatment retention when used during methadone maintenance therapy in patients with opioid use disorder. PROSPERO Registration: CRD42015029372.

Ecological research suggests that increased access to cannabis may facilitate reductions in opioid use and harms, and medical cannabis patients describe the substitution of opioids with cannabis for pain management. However, there is a lack of research using individual-level data to explore this question. We aimed to investigate the longitudinal association between frequency of cannabis use and illicit opioid use among people who use drugs (PWUD) experiencing chronic pain.This study included data from people in 2 prospective cohorts of PWUD in Vancouver, Canada, who reported major or persistent pain from June 1, 2014, to December 1, 2017 (n = 1,152). We used descriptive statistics to examine reasons for cannabis use and a multivariable generalized linear mixed-effects model to estimate the relationship between daily (once or more per day) cannabis use and daily illicit opioid use. There were 424 (36.8%) women in the study, and the median age at baseline was 49.3 years (IQR 42.3-54.9). In total, 455 (40%) reported daily illicit opioid use, and 410 (36%) reported daily cannabis use during at least one 6-month follow-up period. The most commonly reported therapeutic reasons for cannabis use were pain (36%), sleep (35%), stress (31%), and nausea (30%). After adjusting for demographic characteristics, substance use, and health-related factors, daily cannabis use was associated with significantly lower odds of daily illicit opioid use (adjusted odds ratio 0.50, 95% CI 0.34-0.74, p < 0.001). Limitations of the study included self-reported measures of substance use and chronic pain, and a lack of data for cannabis preparations, dosages, and modes of administration.We observed an independent negative association between frequent cannabis use and frequent illicit opioid use among PWUD with chronic pain. These findings provide longitudinal observational evidence that cannabis may serve as an adjunct to or substitute for illicit opioid use among PWUD with chronic pain.

Background: Understanding the potential impact of cannabis use on cardiovascular health is increasingly important as cannabis use rises in the U.S.Objectives: This study evaluated the associations between regular cannabis use, with and without tobacco co-use, and cardiovascular outcomes.Methods: Analysis of a limited dataset obtained through IBM Watson Health Explorys, a platform integrating electronic health record data. Matched controls using Mahalanobis distance within propensity score calipers were defined for: 1) cannabis-using patients (n = 8,944; 43% female); and subgroups of cannabis-using patients: 2) with an encounter diagnosis for tobacco use disorder (TUD; n = 4,682); and 3) without a TUD diagnosis (non-TUD; n = 4,262). Patients had ≥1 blood pressure measurement and blood chemistry lab result in the MetroHealth System (Cleveland, Ohio). Cannabis-using patients had an encounter diagnosis of cannabis abuse/dependence and/or ≥2 cannabis-positive urine drug screens. Control patients, with no cannabis-use-documentation, were matched to the cannabis-using patients on demographics, residential zip code median income, body mass index, and, for the total sample, TUD-status. Outcomes were encounter diagnosis (yes/no) of cerebrovascular accident (CVA), heart arrhythmia, myocardial infarction, subarachnoid hemorrhage (SAH), and all-cause mortality.Results: TUD-patients had the greatest prevalence of cardiovascular disease, regardless of cannabis-use indication. In the total sample and non-TUD subgroup, regular cannabis use was significantly associated with greater risk for CVA, arrhythmia, SAH, and mortality. In the TUD subgroup, regular cannabis use was significantly associated with greater risk for arrhythmia and SAH.Conclusions: Cannabis use is associated with significantly greater risk of adverse cardiovascular diagnoses and overall death, particularly in non-tobacco users.

Psychotic disorders such as schizophrenia are heterogeneous and often debilitating conditions that contribute substantially to the global burden of disease. The introduction of dopamine D2 receptor antagonists in the 1950s revolutionised the treatment of psychotic disorders and they remain the mainstay of our treatment arsenal for psychosis. However, traditional antipsychotics are associated with a number of side effects and a significant proportion of patients do not achieve an adequate remission of symptoms. There is therefore a need for novel interventions, particularly those with a non-D2 antagonist mechanism of action. Cannabidiol (CBD), a non-intoxicating constituent of the cannabis plant, has emerged as a potential novel class of antipsychotic with a unique mechanism of action. In this review, we set out the prospects of CBD as a potential novel treatment for psychotic disorders. We first review the evidence from the perspective of preclinical work and human experimental and neuroimaging studies. We then synthesise the current evidence regarding the clinical efficacy of CBD in terms of positive, negative and cognitive symptoms, safety and tolerability, and potential mechanisms by which CBD may have antipsychotic effects.

In psychiatry, routine EEGs are often abnormal and not very specific, raising questions about the clinical relevance and consequences of potential anomalies. One such question is whether the administration of anticonvulsants would be useful if epileptic discharges are detected in patients without any clinical correlates. With regard to this question, we present a case study in which abnormal EEG patterns were observed in a patient with chronic migraine and cannabis addiction. The patient was a 34-year-old woman with a 14-year history of cannabis abuse who, during withdrawal, showed epileptic spikes, without any corresponding clinical symptoms, and migraine attacks of increasing intensity and frequency. This case study is in line with the new DSM-5 diagnostic tool that for the first time includes the diagnosis of cannabis withdrawal.

Cannabis, the most widely used illicit drug, can induce hallucinations. Our understanding of the biology of cannabis-induced hallucinations (Ca-HL) is limited. We used the Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA) to identify cannabis-induced hallucinations (Ca-HL) among long-term cannabis users (used cannabis ≥1 year and ≥100 times). A genome-wide association study (GWAS) was conducted by analyzing European Americans (EAs) and African Americans (AAs) in Yale-Penn 1 and 2 cohorts individually, then meta-analyzing the two cohorts within population. In the meta-analysis of Yale-Penn EAs (n = 1917), one genome-wide significant (GWS) signal emerged at the CHRM3 locus, represented by rs115455482 (P = 1.66 × 10-10), rs74722579 (P = 2.81 × 10-9), and rs1938228 (P = 1.57 × 10-8); signals were GWS in Yale-Penn 1 EAs (n = 1092) and nominally significant in Yale-Penn 2 EAs (n = 825). Two SNPs, rs115455482 and rs74722579, were available from the Collaborative Study on the Genetics of Alcoholism data (COGA; 3630 long-term cannabis users). The signals did not replicate, but when meta-analyzing Yale-Penn and COGA EAs, the two SNPs' association signals were increased (meta-P-values 1.32 × 10-10 and 2.60 × 10-9, respectively; n = 4291). There were no significant findings in AAs, but in the AA meta-analysis (n = 3624), nominal significance was seen for rs74722579. The rs115455482*T risk allele was associated with lower CHRM3 expression in the thalamus. CHRM3 was co-expressed with three psychosis risk genes (GABAG2, CHRNA4, and HRH3) in the thalamus and other human brain tissues and mouse GABAergic neurons. This work provides strong evidence for the association of CHRM3 with Ca-HL and provides insight into the potential involvement of thalamus for this trait.

Minnesota's medical cannabis program has been praised for being one of the most regulated in the nation. Currently, its use is limited, with one of the reasons being affordability.In Minnesota, patients pay an annual enrollment fee of up to $200, and the cost of the actual product can range from $30 to $300 per unit of sale, which can be compounded by increased dosing frequency or the need for several routes of administration. Between 2017 and 2018, 49.5% of patients enrolled in the medical cannabis program did not renew their enrollment. Although data regarding the reasons for discontinuation are not available, it is reasonable to suspect that cost played a role in some of these patients. In a small survey conducted by the Minnesota Office of Medical Cannabis, cost of product was rated a common reason for uncertainty regarding re-enrollment in the program. Another issue that may also limit the affordability of cannabis in Minnesota is lack of competition. Outside the Minneapolis-St. Paul metropolitan area, the 2 medical cannabis manufacturers are able to operate free from competition, leaving patients with the option to either use that 1 manufacturer or obtain product by illicit means.Nationally, to increase the usability and affordability of medical cannabis, pharmacists should advocate for the relaxation of its controlled substance status. A relaxed status has the potential to increase provider and patient acceptability as well as patient access. In addition, it would allow more research to take place to determine the therapeutic role of cannabis. Finally, it would open the door for prescription drug coverage, which is not without its barriers on a national level. In the meantime, pharmacists in Minnesota should advocate for additional approval of evidence-based indications and an increased number of manufacturers. These changes could increase demand and competition for medical cannabis and drive down prices.

Poor sleep is one of the greatest health problems with social significance whose prevalence started early in adolescence. The relationship between poor sleep quality and the use of alcohol and illicit substances among university students has not been studied. Our study aimed to determine these relationships and the factors influencing the risk of poor sleep in students from health sciences degrees which are the future healthcare providers.A cross-sectional study performed in European university students (n = 676). Sleep quality was assessed by measuring insomnia symptoms with the Athens insomnia scale (AIS). The CRAFFT screening test and AUDIT test were used to measure the use of substances of abuse.Insomnia symptoms were highly prevalent (40.2%) and more common among the youngest students (p = 0.012), who had been studying at the university for less time (p = 0.018), and had high levels of illicit drug use (p = 0.037). Good sleep quality represented a significant protective factor for problematic drug use, with an OR of 0.8 (CI95%: 0.76-0.99). In contrast, the category "not having a job" represents risk 1.2 times higher (CI95%: 1.025-1.557) for problematic drug use. The CRAFFT score significantly predicted higher insomnia symptoms (AIS ≥ 6), yielding an OR of 1.2 (CI95%:1.10-1.32, p < 0.001).Poor sleep quality is common in university students. There is an inverse association between higher insomnia symptoms and illicit drug abuse being a good sleep qualitya protective factor against problematic use of illicit drugs. Several personal and social consequences of illicit drug use are related to poor sleep in this population and it deserves future studies and interventions in order to improve both problems.

Whether medical or recreational cannabis legalization impacts alcohol or cigarette consumption is a key question as cannabis policy evolves, given the adverse health effects of these substances. Relatively little research has examined this question. The objective of this study was to examine whether medical or recreational cannabis legalization was associated with any change in state-level per capita alcohol or cigarette consumption.Dependent variables included per capita consumption of alcohol and cigarettes from all 50 U.S. states, estimated from state tax receipts and maintained by the Centers for Disease Control and National Institute for Alcohol Abuse and Alcoholism, respectively. Independent variables included indicators for medical and recreational legalization policies. Three different types of indicators were separately used to model medical cannabis policies. Indicators for the primary model were based on the presence of active medical cannabis dispensaries. Secondary models used indicators based on either the presence of a more liberal medical cannabis policy ("non-medicalized") or the presence of any medical cannabis policy. Difference-in-difference regression models were applied to estimate associations for each type of policy.Primary models found no statistically significant associations between medical or recreational cannabis legalization policies and either alcohol or cigarette sales per capita. In a secondary model, both medical and recreational policies were associated with significantly decreased per capita cigarette sales compared to states with no medical cannabis policy. However, post hoc analyses demonstrated that these reductions were apparent at least two years prior to policy adoption, indicating that they likely result from other time-varying characteristics of legalization states, rather than cannabis policy.We found no evidence of a causal association between medical or recreational cannabis legalization and changes in either alcohol or cigarette sales per capita.

The presented article describes data from secondary analyses, related to the research article entitled "Cannabis consumption and Non-Alcoholic Fatty Liver Disease. A three years longitudinal study in first episode non-affective psychosis patients" [1]. We present detailed data regarding the socio-demographic and baseline clinical characteristics of a sample of 390 drug-naïve patients with a first episode of non-affective psychosis, and the differences between cannabis users and non-users in those characteristics. Tables also show the results from cross-sectional and longitudinal statistical analyses exploring the relation between cannabis consumption and liver function, after excluding those patients with hazardous alcohol drinking.

Objective: The endocannbinoid system and cannabis exposure has been implicated in emotional processing. The current study examined whether regular cannabis users demonstrated abnormal intrinsic (a.k.a. resting state) frontolimbic connectivity compared to non-users. A secondary aim examined the relationship between cannabis group connectivity differences and self-reported mood and affect symptoms. Method: Participants included 79 cannabis-using and 80 non-using control emerging adults (ages of 18-30), balanced for gender, reading ability, and age. Standard multiple regressions were used to predict if cannabis group status was associated with frontolimbic connectivity after controlling for site, past month alcohol and nicotine use, and days of abstinence from cannabis. Results: After controlling for research site, past month alcohol and nicotine use, and days of abstinence from cannabis, cannabis users demonstrated significantly greater connectivity between left rACC and the following: right rACC (p = 0.001; corrected p = 0.05; f2 = 0.55), left amygdala (p = 0.03; corrected p = 0.47; f2 = 0.17), and left insula (p = 0.03; corrected p = 0.47; f2 = 0.16). Among cannabis users, greater bilateral rACC connectivity was significantly associated with greater subthreshold depressive symptoms (p = 0.02). Conclusions: Cannabis using young adults demonstrated greater connectivity within frontolimbic regions compared to controls. In cannabis users, greater bilateral rACC intrinsic connectivity was associated with greater levels of subthreshold depression symptoms. Current findings suggest that regular cannabis use during adolescence is associated with abnormal frontolimbic connectivity, especially in cognitive control and emotion regulation regions.

Theories of addiction posit that stimuli associated with drug use, including both exteroceptive (e.g., paraphernalia) and interoceptive (e.g., feeling tense or "stressed"), evoke craving and contribute to the pathogenesis of substance misuse. Control over drug cue response and stress is essential for moderating use. Building from laboratory data supporting associations between cue exposure, stress, and craving, this study tested whether these associations generalize to real-world settings and examined whether a well-vetted neurocognitive control capacity, i.e., working memory (WM), moderated associations. Youth (N = 85; 15-24 years) completed baseline and ecological momentary assessments. Cue exposure and participants' average stress predicted higher craving. Youth with weaker WM experienced stronger craving at higher-stress moments but not when faced with cues. Interactions were present for both previous-moment and same-moment stress. Craving among adolescents with stronger WM was not swayed by momentary stress. Findings suggest stronger WM protects against craving at more stressful moments.

Autism Spectrum Disorders comprise conditions that may affect cognitive development, motor skills, social interaction, communication, and behavior. This set of functional deficits often results in lack of independence for the diagnosed individuals, and severe distress for patients, families, and caregivers. There is a mounting body of evidence indicating the effectiveness of pure cannabidiol (CBD) and CBD-enriched Cannabis sativa extract (CE) for the treatment of autistic symptoms in refractory epilepsy patients. There is also increasing data support for the hypothesis that non-epileptic autism shares underlying etiological mechanisms with epilepsy. Here we report an observational study with a cohort of 18 autistic patients undergoing treatment with compassionate use of standardized CBD-enriched CE (with a CBD to THC ratio of 75/1). Among the 15 patients who adhered to the treatment (10 non-epileptic and five epileptic) only one patient showed lack of improvement in autistic symptoms. Due to adverse effects, three patients discontinued CE use before 1 month. After 6-9 months of treatment, most patients, including epileptic and non-epileptic, showed some level of improvement in more than one of the eight symptom categories evaluated: Attention Deficit/Hyperactivity Disorder; Behavioral Disorders; Motor Deficits; Autonomy Deficits; Communication and Social Interaction Deficits; Cognitive Deficits; Sleep Disorders and Seizures, with very infrequent and mild adverse effects. The strongest improvements were reported for Seizures, Attention Deficit/Hyperactivity Disorder, Sleep Disorders, and Communication and Social Interaction Deficits. This was especially true for the 10 non-epileptic patients, nine of which presented improvement equal to or above 30% in at least one of the eight categories, six presented improvement of 30% or more in at least two categories and four presented improvement equal to or above 30% in at least four symptom categories. Ten out of the 15 patients were using other medicines, and nine of these were able to keep the improvements even after reducing or withdrawing other medications. The results reported here are very promising and indicate that CBD-enriched CE may ameliorate multiple ASD symptoms even in non-epileptic patients, with substantial increase in life quality for both ASD patients and caretakers.

AKB48 is a designer drug belonging to the indazole synthetic cannabinoids class, illegally sold as herbal blend, incense, or research chemicals for their psychoactive cannabis-like effects. In the present study, we investigated the in vivo pharmacological and behavioral effects of AKB48 in male rats and measured the pharmacodynamic effects of AKB48 and simultaneously determined its plasma pharmacokinetic. AKB48 at low doses preferentially stimulated dopamine release in the nucleus accumbens shell (0.25 mg/kg) and impaired visual sensorimotor responses (0.3 mg/kg) without affecting acoustic and tactile reflexes, which are reduced only to the highest dose tested (3 mg/kg). Increasing doses (0.5 mg/kg) of AKB48 impaired place preference and induced hypolocomotion in rats. At the highest dose (3 mg/kg), AKB48 induced hypothermia, analgesia, and catalepsy; inhibited the startle/pre-pulse inhibition test; and caused cardiorespiratory changes characterized by bradycardia and mild bradipnea and SpO2 reduction. All behavioral and neurochemical effects were fully prevented by the selective CB1 receptor antagonist/inverse agonist AM251. AKB48 plasma concentrations rose linearly with increasing dose and were correlated with changes in the somatosensory, hypothermic, analgesic, and cataleptic responses in rats. For the first time, this study shows the pharmacological and behavioral effects of AKB48 in rats, correlating them to the plasma levels of the synthetic cannabinoid. Chemical Compound Studied in This Article: AKB48 (PubChem CID: 57404063); AM251 (PubChem CID: 2125).

Concomitant use of cannabis and other psychoactive substances is common and it is often difficult to differentiate its acute effects from those of other substances. This study aimed to characterize the acute toxicity of cannabis with and without co-use of other substances.Retrospective analysis of cases presenting at the emergency departments of three large hospitals in Switzerland due to acute toxicity related to cannabis recreational use.Among 717 attendances related to acute cannabis toxicity, 186 (26 %) were due to use of cannabis alone. The median patient age was 26 years (range 14-68), and 73 % were male. Commonly reported symptoms/signs in lone-cannabis cases included nausea/vomiting (26 %), palpitations (25 %), anxiety (23 %), and chest pain (15 %); there were no fatalities and most intoxications were of minor severity (61 %). Most patients (83 %) using cannabis alone were discharged from the emergency department, 8 % were referred to psychiatric, and two (1 %) to the intensive care; severe complications included psychosis (7 %), coma (6 %), and seizures (5 %) and one patient (<1 %) required intubation. Lone-cannabis patients presented more often with palpitations, anxiety, panic attacks, and chest pain than patients in the co-use group, whereas the latter presented more often with impaired consciousness, agitation, respiratory depression and hallucinations, and were more often admitted to psychiatric or intensive care.Intoxication with cannabis alone was mostly associated with minor toxicity. Nevertheless, severe complications and cases requiring admission to intensive or psychiatric care were also reported, which indicates that intoxication with cannabis alone does not exclude considerable health risks.

The effects of cannabis reported by users range from experiences of euphoria and anxiolytic effects to paranoia, anxiety, and increased risk of depression. Attempts to reconcile the apparent contradictions in user response have not been conclusive. Here, we utilized selectively-bred stress-resilient socially dominant (Dom) and stress-sensitive socially submissive (Sub) mice to elucidate this contradiction. Following short-term, repeated treatment with delta-9-tetrahydrocannabinol (THC) at two different doses (1.5 mg/kg and 15 mg/kg), Sub mice presented significant place-aversion in a Conditioned Place Preference paradigm at a high dose, whereas Dom mice displayed no place preference or aversion. Forced Swim test conducted after 6-week of washout period, revealed differential impact of the two THC doses depending upon behavioral pattern. Specifically, the low dose alleviated depressive-like behavior in Sub mice, while the high dose produced the opposite effect in Dom mice. Interestingly, corticosterone concentration in serum was elevated at the high dose regardless of the mice-population tested. We conclude here that differences in dominance behavior and stress vulnerability are involved in the regulation of cannabis response among users and should be considered when prescribing THC-containing medications to patients.

Attention-deficit hyperactivity disorder (ADHD) has consistently been associated with substance use, but the nature of this association is not fully understood. To inform intervention development and public health messages, a vital question is whether there are causal pathways from ADHD to substance use and/or vice versa. We applied bidirectional Mendelian randomization, using summary-level data from the largest available genome-wide association studies (GWAS) on ADHD, smoking (initiation, cigarettes per day, cessation, and a compound measure of lifetime smoking), alcohol use (drinks per week, alcohol problems, and alcohol dependence), cannabis use (initiation), and coffee consumption (cups per day). Genetic variants robustly associated with the "exposure" were selected as instruments and identified in the "outcome" GWAS. Effect estimates from individual genetic variants were combined with inverse-variance weighted regression and five sensitivity analyses (weighted median, weighted mode, MR-Egger, generalized summary data-based MR, and Steiger filtering). We found evidence that liability to ADHD increases likelihood of smoking initiation and heaviness of smoking among smokers, decreases likelihood of smoking cessation, and increases likelihood of cannabis initiation. There was weak evidence that liability to ADHD increases alcohol dependence risk but not drinks per week or alcohol problems. In the other direction, there was weak evidence that smoking initiation increases ADHD risk, but follow-up analyses suggested a high probability of horizontal pleiotropy. There was no clear evidence of causal pathways between ADHD and coffee consumption. Our findings corroborate epidemiological evidence, suggesting causal pathways from liability to ADHD to smoking, cannabis use, and, tentatively, alcohol dependence. Further work is needed to explore the exact mechanisms mediating these causal effects.

Glutamatergic plasticity in the nucleus accumbens core (NAcore) is a key neuronal process in appetitive learning and contributes to pathologies such as drug addiction. Understanding how this plasticity factors into cannabis addiction and relapse has been hampered by the lack of a rodent model of cannabis self-administration. We used intravenous self-administration of two constituents of cannabis, Δ9 -tetrahydrocannabinol (THC) and cannabidiol (CBD) to examine how contingent cannabis use and cue-induced cannabinoid-seeking alters glutamatergic neurotransmission and synaptic plasticity in NAcore. NMDA receptor (NMDAR)-dependent long-term depression (LTD) in the NAcore was lost after cannabinoid, but not sucrose self-administration. Surprisingly, when rats underwent cue-induced cannabinoid seeking, LTD was restored. Loss of LTD was accompanied by desensitization of cannabinoid receptor 1 (CB1R). CB1R are positioned to regulate synaptic plasticity by being expressed on glutamatergic terminals and negatively regulating presynaptic excitability and glutamate release. Supporting this possibility, LTD was restored by promoting CB1R signaling with the CB1 positive allosteric modulator GAT211. These data implicate NAcore CB1R as critical regulators of metaplasticity induced by cannabis self-administration and the cues predicting cannabis availability.

Cannabis use is widespread among people at ultra-high risk (UHR) for psychosis. The causal link as well as the temporal link between cannabis use and further occurrence of psychosis in UHR people remain inconclusive. Current science data supported an increased risk of transition to psychosis in cannabis users who are genetically predisposed to psychosis. This risk would be even greater in the presence of a family history of psychosis, in case of a strong use and an early onset use. Several models have been cited to explain the link between cannabis use and the subsequent onset of psychosis or prepsychotic states: cannabis-induced modifications of some brain structures, a dysregulation of the hypothalamic-pituitary axis and an alteration of normal neurological development via the endocannabinoid system. Cannabis represents a modifiable risk for psychosis. Current interventions aim to reduce or stop the cannabis use in order to reduce the risk of transition to psychosis.

The use of electronic cigarettes has become relatively popular in France since 2010, including among adolescents. However, its use in relation to smoking and other factors is not well understood today.The data come from the ESCAPAD 2017 survey, a nationally representative cross-sectional survey taking place at a 1-day session of civic and military information compulsory for all French nationals around 17 (39,115 respondents). Descriptive analyses and multivariate regressions were undertaken to describe the recent use of e-cigarette at 17 and its associated factors.e-cigarettes were experimented by 52.4 % of 17 year-olds, and used by 16.8 % in the preceding month, 1.9 % daily. Most recent users were also daily smokers (62.5 %), and only 7.6 % had never experimented cigarettes before. Among those who experimented with both products, only 13.3 % tried e-cigarettes before cigarettes. The associated uses of other products were the most striking factors: daily smoking (relative risk [RR]=2.73), ever use of hookah (RR=2.31), cannabis use in the last year (RR=1.60), regular alcohol drinking (RR=1.20) and ever use of another illicit drug (RR=1.11). Recent vapers that were also daily smokers had a more pronounced sociodemographic profile and a higher level of other drugs consumptions than recent vapers only.Although a majority of French adolescents experiment with vaping, they are fewer to use it regularly and its current use is frequently associated with daily smoking. Future trends and the relationship between smoking and vaping among adolescents will have to be further investigated, including the motivations of its use.

Background and Objectives: Psychological outcomes following termination of wanted pregnancies have not previously been studied. Does excluding such abortions affect estimates of psychological distress following abortion? To address this question this study examines long-term psychological outcomes by pregnancy intention (wanted or unwanted) following induced abortion relative to childbirth in the United States. Materials and Methods: Panel data on a nationally-representative cohort of 3935 ever-pregnant women assessed at mean age of 15, 22, and 28 years were examined from the National Longitudinal Survey of Adolescent to Adult Health (Add Health). Relative risk (RR) and incident rate ratios (IRR) for time-dynamic mental health outcomes, conditioned by pregnancy intention and abortion exposure, were estimated from population-averaged longitudinal logistic and Poisson regression models, with extensive adjustment for sociodemographic differences, pregnancy and mental health history, and other confounding factors. Outcomes were assessed using the Diagnostic and Statistical Manual, Version 4, American Psychiatric Association (DSM-IV) diagnostic criteria or another validated index for suicidal ideation, depression, and anxiety (affective problems); drug abuse, opioid abuse, alcohol abuse, and cannabis abuse (substance abuse problems); and summary total disorders. Results: Women who terminated one or more wanted pregnancies experienced a 43% higher risk of affective problems (RR 1.69, 95% CI 1.3-2.2) relative to childbirth, compared to women terminating only unwanted pregnancies (RR 1.18, 95% CI 1.0-1.4). Risks of depression (RR 2.22, 95% CI 1.3-3.8) and suicidality (RR 3.44 95% CI 1.5-7.7) were especially elevated with wanted pregnancy abortion. Relative risk of substance abuse disorders with any abortion was high, at about 2.0, but unaffected by pregnancy intention. Excluding wanted pregnancies artifactually reduced estimates of affective disorders by 72% from unity, substance abuse disorders by 11% from unity, and total disorders by 21% from unity. Conclusions: Excluding wanted pregnancies moderately understates overall risk and strongly understates affective risk of mental health difficulties for women following abortion. Compared to corresponding births, abortions of wanted pregnancies are associated with a greater risk of negative psychological affect, particularly depression and suicide ideation, but not greater risk of substance abuse, than are abortions of unwanted pregnancies. Clinical, research, and policy implications are discussed briefly.

Sense of acceptance is conceived as a central component of perceived social support and is thought to be a key resilience factor for adjustment during transition to university. The current study examines how a binge drinking pattern of alcohol consumption and the co-consumption of binge drinking and cannabis in first-year university students are related to perceived acceptance from family, mother, father, and friends. The study sample consisted of 268 women and 216 men, of average age 18.25 years (SE = 0.01), enrolled in the first year of different degree courses at the University of Santiago de Compostela. Participants were classified in three groups (control, binge drinking, polyconsuming) on the basis of the Timeline Followback for alcohol and cannabis. Perceived sense of acceptance was measured using the Perceived Acceptance Scale. Analysis of the data revealed that perceived acceptance was lower in polyconsuming students than in the binge drinking and control groups (p < 0.05; with η2 ranging between 0.009 and 0.020). A curvilinear relationship between binge drinking and perceived acceptance from friends was identified. Social support should be considered in future investigations and interventions as a vulnerability marker for detrimental consequences of substance use and risk of consumption disorders, as well as adolescent maladjustment.

Background: Vaping has become an increasingly common mode of administration for both nicotine and cannabis, with overlap among users, devices, as well as nicotine and cannabis companies. There is a need to understand patterns of use among youth, including the way nicotine and cannabis are administered. Methods: Data are from Wave 2 of the ITC Youth Tobacco and Vaping survey, an online survey conducted in 2018 among 16-19 year-olds recruited from commercial panels in Canada (n = 3757), England (n = 3819), and the U.S. (n = 3961). The prevalence of past 30-day vaping nicotine, non-nicotine and cannabis substances, as well as cannabis modes of use was examined. Logistic regression models examined between country differences in prevalence. Results: Past 30-day cannabis use was highest among Canadian youth (16.6%), followed by youth in the U.S. (13.8%) and England (9.0%). Vaping e-cigarettes was substantially more prevalent than vaping cannabis in all three countries. All forms of cannabis use were higher among Canadian and U.S. youth compared to England (p < 0.001 for all). Past 30-day cannabis users in the U.S. were more likely to report vaping cannabis oil (30.1%), and consuming solid concentrates such as wax and shatter (30.2%), compared to cannabis users in Canada (18.6% and 22.9%) and England (14.3% and 11.0%; p < 0.001 for all). Conclusions: Youth are administering cannabis and nicotine using a wide diversity of modes. Cannabis users in the U.S.-where an increasing number of states have legalized medical and non-medical cannabis-reported notably higher use of more potent cannabis products, including cannabis oils and extracts.

This paper aimed to systematically examine the efficacy and adverse event (AE) profile of cannabidiol and medicinal cannabis by analyzing qualitative and meta-analytic data. We used the terms ("Cannabidiol" OR "Cannabis") AND "Epilepsy" AND ("Treatment" OR "Therapeutics") as keywords to retrieve studies indexed on PubMed, ScienceDirect, and CENTRAL databases. The inclusion criteria were as follows: clinical studies with a longitudinal observational design and intervention using cannabinoid derivatives, especially cannabidiol and medicinal cannabis, whereby some results involved the frequency of epileptic seizures. We used Cochrane Collaboration's Review Manager software (RevMan 5.1.6) for the meta-analysis and dichotomized the articles to a confidence interval of 95%. From 236 articles, we selected 16 for descriptive analysis; we selected only 4 for the meta-analysis. According to the results, a statistically meaningful effect of cannabidiol compared with placebo was observed (p < 0.00001). When comparing treatment with cannabidiol or medicinal cannabis, significance was not found for the AE profile (p = 0.74). As AEs for cannabidiol were more common under short-term than under long-term treatment (p < 0.00001), this approach was favorable in the long term. Furthermore, cannabidiol is more effective than placebo, regardless of the etiology of epileptic syndromes and dosage. Overall, the AE profile did not differ across treatments with cannabidiol or medicinal cannabis, though it did differ favorably for long-term than for short-term treatment.

The increasing use of synthetic cannabinoids (SCBs) in recreational settings is becoming a new paradigm of drug abuse. Although SCBs effects mimic those of the Cannabis sativa plant, these drugs are frequently more potent and hazardous. It is known that endocannabinoid signalling plays a crucial role in diverse reproductive events such as placental development. Moreover, the negative impact of the phytocannabinoid Δ9-tetrahydrocannabinol (THC) in pregnancy outcome, leading to prematurity, intrauterine growth restriction and low birth weight is well recognized, which makes women of childbearing age a sensitive group to developmental adverse effects of cannabinoids. Placental trophoblast turnover relies on regulated processes of proliferation and apoptosis for normal placental development. Here, we explored the impact of the SCBs JWH-018, JWH-122 and UR-144 and of the phytocannabinoid THC in BeWo cell line, a human placental cytotrophoblast cell model. All the cannabinoids caused a significant decrease in cell viability without LDH release, though this effect was only detected for the highest concentrations of THC. Moreover, a cell cycle arrest at the G2/M phase was also observed. JWH-018 and JWH-122 increased reactive oxygen species (ROS) production and THC, UR-144 and JWH-122 caused loss of mitochondrial membrane potential. All the compounds were able to induce caspase-9 activation. The involvement of apoptotic pathways was further confirmed through the significant increase in caspase -3/-7 activities. For UR-144, this effect was reversed by the CB1 antagonist AM281, for JWH-018 and THC this effect was mediated by both cannabinoid receptors CB1 and CB2 while for JWH-122 it was cannabinoid receptor-independent. This work demonstrates that THC and SCBs are able to induce apoptotic cell death. Although they may act through different mechanisms and potencies, the studied cannabinoids have the potential to disrupt gestational fundamental events.

It is well established that cannabis use promotes appetite. However, how cannabis interacts with the brain's appetite center, the hypothalamus, to stimulate feeding behavior is unknown. A growing body of evidence indicates that the hypothalamic transcriptome programs energy balance. Here, we tested the hypothesis that cannabis targets alternative polyadenylation (APA) sites within hypothalamic transcripts to regulate transcriptomic function. To do this, we used a novel cannabis vapor exposure model to characterize feeding in adult male Long Evans rats and aligned this behavioral response with APA events using a Whole Transcriptome Termini Sequencing (WTTS-Seq) approach as well as functional RNA abundance measurements with real-time quantitative polymerase chain reactions. We found that vapor cannabis exposure promoted food intake in free-feeding and behaviorally sated rats, validating the appetite stimulating properties of cannabis. Our WTTS-Seq analysis mapped 59 unique cannabis-induced hypothalamic APAs that occurred primarily within exons on transcripts that regulate synaptic function, excitatory synaptic transmission, and dopamine signaling. Importantly, APA insertions regulated RNA abundance of Slc6a3, the dopamine transporter, suggesting a novel genetic link for cannabis regulation of brain monoamine function. Collectively, these novel data indicate that a single cannabis exposure rapidly targets a key RNA processing mechanism linked to brain transcriptome function.

Cannabis use patterns vary considerably, with many users reporting simultaneous and non-simultaneous use (co-use) of other substances. Despite this, little research has examined the extent to which subtypes of cannabis users may be identified based on their simultaneous and co-use behaviors.The sample consisted of adult Australian twins and siblings who reported lifetime cannabis use (n = 2590). A latent class analysis was conducted to determine subtypes of cannabis users based on five indicators of substance co-use and simultaneous use. Adolescent correlates (age of substance initiation and conduct disorder) and adult correlates (substance use/disorder and depression) of class membership were assessed. Twin similarity for class membership was also examined.Four subtypes of users were identified: 1) alcohol co-users, 2) simultaneous alcohol users, 3) simultaneous tobacco users, and 4) simultaneous alcohol, tobacco, and drug users. Compared to co-users of alcohol, simultaneous alcohol users were at increased risk for alcohol problems. Patterns of use that involved simultaneous tobacco and cannabis use (i.e., simultaneous tobacco users and simultaneous alcohol, tobacco, and drug users) were associated with the most problematic outcomes, including substance use and disorder. There was evidence for genetic influences (12-58%) on cannabis use patterns, with higher concordance for latent class membership among monozygotic compared to dizygotic twins (χ2 (1) = 7.19, p = 0.007).The current study identified four classes of cannabis users at varying degrees of risk. Results suggest that simultaneous tobacco and cannabis use may be especially associated with deleterious outcomes.

The United States is experiencing an unprecedented outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI) (1). All EVALI patients have used e-cigarette, or vaping, products, and most (≥85%) have reported using products containing tetrahydrocannabinol (THC) (2,3), the principal psychoactive component of cannabis. To examine whether e-cigarette, or vaping, product use behaviors differed between adult EVALI patients and adults who use these products but have not developed lung injury, the Illinois Department of Public Health (IDPH) conducted an online public survey during September-October 2019 targeting e-cigarette, or vaping, product users in Illinois. Among 4,631 survey respondents, 94% reported using any nicotine-containing e-cigarette, or vaping, products in the past 3 months; 21% used any THC-containing products; and 11% used both THC-containing products and nicotine-containing products. Prevalence of THC-containing product use was highest among survey respondents aged 18-24 years (36%) and decreased with increasing age. E-cigarette, or vaping, product use behaviors of 66 EVALI patients aged 18-44 years who were interviewed as part of the ongoing outbreak investigation were compared with a subset of 519 survey respondents aged 18-44 years who reported use of THC-containing e-cigarette, or vaping, products. Compared with these survey respondents, EVALI patients had higher odds of reporting exclusive use of THC-containing products (adjusted odds ratio [aOR] = 2.0, 95% confidence interval [CI] = 1.1-3.6); frequent use (more than five times per day) of these products (aOR = 3.1, 95% CI = 1.6-6.0), and obtaining these products from informal sources, such as a dealer, off the street, or from a friend (aOR = 9.2, 95% CI = 2.2-39.4). The odds of using Dank Vapes, a class of largely counterfeit THC-containing products, was also higher among EVALI patients (aOR = 8.5, 95% CI = 3.8-19.0). These findings reinforce current recommendations not to use e-cigarette, or vaping, products that contain THC and not to use any e-cigarette, or vaping, products obtained from informal sources. In addition, because the specific compound or ingredient causing lung injury is not yet known, CDC continues to recommend that persons consider refraining from use of all e-cigarette, or vaping, products while the outbreak investigation continues (1).

It is unknown whether cannabis users self-medicating their inflammatory bowel disease (IBD) symptoms are more likely to have comorbid mental health or personality risk factors associated with an increased potential for substance misuse compared with recreational cannabis users.We surveyed individuals with IBD about their cannabis use, their mental health symptoms, and personality risk factors associated with substance misuse. We compared risk factors for substance misuse between individuals using cannabis to manage IBD symptoms and those using cannabis recreationally.Of 201 persons with IBD who completed the questionnaire, 108 reported lifetime cannabis use. Of those, a larger proportion of Crohn's disease patients used cannabis to manage IBD symptoms (53% [34/64] vs 28% [12/43]; P = 0.010). Individuals self-medicating with cannabis were more likely to use cannabis for coping reasons (P = 0.016) and demonstrated higher levels of impulsivity (P = 0.004) and depressive symptoms (P = 0.012) when compared with individuals using cannabis recreationally. Logistic regression revealed that cannabis was 4.1 times (P = 0.05) and 3.7 times (P = 0.05) more likely to be used for IBD symptoms by smokers and individuals with moderate-severe depressive symptoms, respectively. Individuals high in impulsivity were 4.1 times more likely to use cannabis for their IBD symptoms than those low in impulsivity (P = 0.005).Persons with IBD self-medicating with cannabis have characteristics associated with increased vulnerability to substance misuse when compared with those using cannabis recreationally. Screening for mental health comorbidities and vulnerability to substance misuse should be undertaken if cannabis is to be used to treat IBD symptoms.

Legalization of medical cannabis has occurred in 33 states and the District of Columbia, and recreational use has increased exponentially since 2013. As a result, it is important to understand how cannabis interacts with other drugs and has potential risks for patients on concomitant medications. Components of medical cannabis can inhibit or compete for several cytochrome P450 (CYP) hepatic isoenzymes, UDP-glucuronosyltransferases, and P-glycoprotein. These enzymes and transporters are involved in the metabolism and absorption of numerous medications, including anticoagulants (ACs) and antiplatelet agents (APs), potentially causing harmful drug-drug interactions. ACs and/or APs are often prescribed to high-risk patients with cardiac conditions, a history of myocardial infarction, or stroke. Cannabis may cause these medications to be less efficacious and put patients at risk for recurrent cardiovascular and cerebrovascular events. Several case reports show cannabis may inhibit the metabolism of warfarin because of CYP2C9 interactions, resulting in increased plasma concentrations, increased international normalized ratio, and risk of bleeding. Cannabidiol inhibits CYP2C19, an isoenzyme responsible for the transformation of clopidogrel to its active thiol metabolite. This interaction could lead to subtherapeutic levels of active metabolite and possibly increased stroke risk. Within this review, a total of 665 articles were screened from PubMed and EMBASE. Four case reports, 1 in vitro study, and 1 pharmacokinetic article were found to be of relevance. This review serves to examine reported and potential cannabis interactions with APs/ACs to help inform patients and health care providers of possible risks and knowledge gaps.

The objective of this study was to conduct a review of the benefits and adverse effects of cannabis (or marijuana) legalization in various states across the US. The current study offers a preliminary evaluation of the problems concerning marijuana legalization in several states, with the primary goal being the assessment of the impact of laws and policies governing the legalization and use of marijuana for medical purposes. A comprehensive search on cannabis and its derivatives was performed using multiple resource databases: PubMed, MEDLINE, Embase, PsycINFO, CENTRAL (Cochrane Controlled Register of Trials), government web sources, and the Department of Public Health databases. A total of 47 reports that evaluated the effects of cannabis legalization were included in this review. All review stages were conducted independently by two reviewers. Data were extracted in standardized tables by one reviewer and adjusted by a second, which were verified by the third author. We examined the use of cannabis before and after the changes in policy and the impact of marijuana legalization on traffic safety, behavior and educational achievement in adolescents, public health, tax revenues, criminal justice expenditures, and financial outcomes. We analyzed the effects and consequences of marijuana use in states that have or have not legalized marijuana. This report also includes the responsiveness of the people in states where marijuana is legalized and its value in the healthcare system. Our study highlights the existing limitations of reviews that probe the effect of decriminalizing marijuana in some states of the country. Our analysis shows that detailed and precise evaluation of policy dynamics must be conducted, taking into account the heterogeneity in population sub-groups and policies. Accordingly, in states where marijuana is used for its medicinal value and recreational purposes, people have different views on the legalization of marijuana. The complete effect of legalizing and commercializing marijuana on consumers' mental health and their educational outcomes is expected to take a longer duration prior to its achievement; unfortunately, fewer merits are anticipated. Most of the reports evaluated in this article proved to be marred with inconsistencies. Many of the stated claims did not pass a methodical evaluation. Going forward, additional data from available sources will lead to stronger conclusions. We weighed the pros and cons of marijuana legalization. However, we are certain that consumers can make better decisions by weighing each opinion by its reliability and safety.

There is extensive evidence to believe that the endocannabinoid system plays an important role in energy homeostasis through a variety of mechanisms. This study aimed to analyze the association between polymorphism rs12720071 of the cannabinoid type 1 receptor (CNR1) gene with dyslipidemia and overweight in young, healthy Mexicans. The association was analyzed with a logistic regression model and expressed as odds ratio (OR). A total of 148 individuals agreed to participate. Overall, the serum concentrations of lipids were found to be in the normal range. However, females presented higher levels of cholesterol and low-density lipoprotein (LDL) than males [probability value (p) = <0.05]. In addition, females presented higher risk of being overweight (BMI: >25) [OR = 3.57; 95% confidence interval (CI): 1.05-12.20; p = 0.04], than males. Our results suggest that this polymorphism could influence BMI in young females.

Cannabis is one of the most commonly used illicit drugs and is now legally used recreationally or medicinally in more than half of the United States. Cannabis use has been proposed as a cause of acute pancreatitis in patients with no other identifiable etiology. Our case highlights acute pancreatitis in a young male patient with no medical problems. It is important to identify the etiology in acute pancreatitis to prevent recurrence and complications.

This study sought to determine the prevalence, tolerability, and self-reported effectiveness of cannabis in women with endometriosis.A cross-sectional online survey was conducted between October and December 2017. Recruitment targeted women with endometriosis through social media postings from endometriosis advocacy groups. Women aged 18 to 45, living in Australia, and with surgically confirmed endometriosis were eligible to participate. Survey questions investigated the types of self-management used, change in symptoms or medication use, costs, and adverse events.A total of 484 responses were included for analysis, with 76% of the women reporting the use of general self-management strategies within the last 6 months. Of those using self-management, 13% reported using cannabis for symptom management. Self-reported effectiveness in pain reduction was high (7.6 of 10), with 56% also able to reduce pharmaceutical medications by at least half. Women reported the greatest improvements in sleep and in nausea and vomiting. Adverse effects were infrequent (10%) and minor.Australian law currently requires legal medicinal cannabis use to follow specific, regulated pathways that limit prescription by this method; however, self-reported illicit use of cannabis remains relatively common in Australian women with endometriosis. Women report good efficacy of cannabis in reducing pain and other symptoms, with few adverse effects reported. Further clinical research is warranted to determine the effectiveness of cannabis in managing endometriosis symptoms. In locations where medicinal cannabis is more accessible, there remains a paucity of evidence for its clinical efficacy with endometriosis-associated symptoms.

Little is known about changes in marijuana use and cannabis use disorder (CUD) after recreational marijuana legalization (RML).To examine the associations between RML enactment and changes in marijuana use, frequent use, and CUD in the United States from 2008 to 2016.This survey study used repeated cross-sectional survey data from the National Survey on Drug Use and Health (2008-2016) conducted in the United States among participants in the age groups of 12 to 17, 18 to 25, and 26 years or older.Multilevel logistic regression models were fit to obtain estimates of before-vs-after changes in marijuana use among respondents in states enacting RML compared to changes in other states.Self-reported past-month marijuana use, past-month frequent marijuana use, past-month frequent use among past-month users, past-year CUD, and past-year CUD among past-year users.The study included 505 796 respondents consisting of 51.51% females and 77.24% participants 26 years or older. Among the total, 65.43% were white, 11.90% black, 15.36% Hispanic, and 7.31% of other race/ethnicity. Among respondents aged 12 to 17 years, past-year CUD increased from 2.18% to 2.72% after RML enactment, a 25% higher increase than that for the same age group in states that did not enact RML (odds ratio [OR], 1.25; 95% CI, 1.01-1.55). Among past-year marijuana users in this age group, CUD increased from 22.80% to 27.20% (OR, 1.27; 95% CI, 1.01-1.59). Unmeasured confounders would need to be more prevalent in RML states and increase the risk of cannabis use by 1.08 to 1.11 times to explain observed results, indicating results that are sensitive to omitted variables. No associations were found among the respondents aged 18 to 25 years. Among respondents 26 years or older, past-month marijuana use after RML enactment increased from 5.65% to 7.10% (OR, 1.28; 95% CI, 1.16-1.40), past-month frequent use from 2.13% to 2.62% (OR, 1.24; 95% CI, 1.08-1.41), and past-year CUD from 0.90% to 1.23% (OR, 1.36; 95% CI, 1.08-1.71); these results were more robust to unmeasured confounding. Among marijuana users in this age group, past-month frequent marijuana use and past-year CUD did not increase after RML enactment.This study's findings suggest that although marijuana legalization advanced social justice goals, the small post-RML increase in risk for CUD among respondents aged 12 to 17 years and increased frequent use and CUD among adults 26 years or older in this study are a potential public health concern. To undertake prevention efforts, further studies are warranted to assess how these increases occur and to identify subpopulations that may be especially vulnerable.

This study aimed at assessing developmental trajectories of risk behaviors from adolescence into young adulthood and their associations with outcomes in young adulthood (i.e. education, employment). Data of the TRacking Adolescents' Individual Lives Survey (TRAILS) including 2,149 participants (mean age = 13.6, SD = 0.5, 51% girls) were used to examine the development of alcohol, cannabis, smoking, and externalizing behavior. The results showed that the associations between these risk behaviors varied with age, and revealed varying developmental patterns throughout adolescence. Most notably alcohol use did not covary strongly with the other risk behaviors. The often assumed peak in risk behavior in adolescence was only found in a small group, and only for alcohol (7.4%) and cannabis use (3.4%), but not for smoking or externalizing behavior. Most adolescents revealed only low involvement in risk behavior, with the largest differences between low and high trajectories emerging in late adolescence (> 19 years). Clustering of risk behavior throughout adolescence is rather the exception than the rule and depends on age and type of risk behavior. Differences in risk behavior between individuals become the largest in late adolescence, possibly influencing successful transition into adulthood visible in educational attainment and employment.

Marijuana, derived from the Cannabis sativa plant, is the most commonly abused illicit drug in the United States. Now, more than ever, due to changing regulations, marijuana is more readily available and is known to be habitually used by millions. The neuropsychiatric effects of marijuana are well-known which include chronic fatigue syndrome and polyphagia. However, marijuana is also known to exert cardiac effects, such as tachycardia, hypotension, and hypertension. Marijuana has also been described in association with atrial fibrillation, ventricular tachycardia, and cardiac arrest. However, acute coronary syndromes, such as myocardial infarction in the setting of marijuana use, is rare. Herein, we present the case of a non-ST-elevation myocardial infarction (NSTEMI) in the setting of marijuana use in a 42-year-old African American male with no significant past medical history who presented with chest pain at rest one hour after smoking marijuana.

Cannabinoids are the main medicinal compounds of interest in the plant Cannabis sativa, that are primarily synthesised in the glandular trichomes; found on female floral buds. The content, composition and yield of secondary metabolites (cannabinoids and terpenoids) is influenced by the plant's genetics and environment. Some initial gene expression experiments have been performed from strains of this plant species that contrasted in cannabinoid production, however the present knowledge about detailed trichome transcriptomics in this species is limited. An extensive transcriptome atlas was generated by RNA sequencing using root, shoot, flower and trichome tissues from a female plant strain (Cannbio-2) and was enhanced with the addition of vegetative and reproductive tissues from a male cannabis plant. Differential gene expression analysis identified genes preferentially expressed in different tissues. Detailed trichomics was performed from extractions specifically from glandular trichomes as well as female floral tissues at varying developmental stages, to identify stage-specific differentially expressed genes. Candidate genes involved in terpene and cannabinoid synthesis were identified and the majority were found to have an abundant expression in trichomes. The comprehensive transcriptome is a significant resource in cannabis for further research of functional genomics to improve the yield of specialised metabolites with high pharmacological value.

The aim of this study was to elucidate the pathway of associations linking gambling, alcohol intake, smoking habit, cannabis consumption between each other and with demographic and socioeconomic variables.A survey was conducted in 2017 on a representative sample of 15 602 Italian 14-year-olds to 17-year-olds attending 201 secondary schools.Structural Equation Models analysis was used to assess the pathway between gambling, alcohol intake, smoking, cannabis consumption, demographics and socioeconomic factors.Irrespective of socioeconomic or demographic variables, gambling is positively associated with alcohol and cannabis consumption, while cannabis consumption is predicted by smoking and by alcohol intake, smoking is predicted by alcohol intake. Adolescents with a higher weekly income are more at risk of gambling, drinking alcohol and smoking, while the degree of economic dissatisfaction was positively associated with alcohol intake, cannabis consumption and smoking. Maternal employment appeared to be positively associated with adolescents' smoking, alcohol intake and cannabis consumption.This is one of the first studies to shed light on the pathways of associations connecting various health-risk behaviours among adolescents with demographic and socioeconomic factors.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with no known cure and with an average life expectancy of 3-5 years post diagnosis. The use of complementary medicine such as medicinal cannabis in search for a potential treatment or cure is common in ALS. Preclinical studies have demonstrated the efficacy of cannabinoids in extending the survival and slowing of disease progression in animal models with ALS. There are anecdotal reports of cannabis slowing disease progression in persons with ALS (pALS) and that cannabis alleviated the symptoms of spasticity and pain. However, a clinical trial in pALS with these objectives has not been conducted.The Efficacy of cannabis-based Medicine Extract in slowing the disease pRogression of Amyotrophic Lateral sclerosis or motor neurone Disease trial is a randomised, double-blind, placebo-controlled cannabis trial in pALS conducted at the Gold Coast University Hospital, Australia. The investigational product will be a cannabis-based medicine extract (CBME) supplied by CannTrust Inc., Canada, with a high-cannabidiol-low-tetrahydrocannabinol concentration. A total of 30 pALS with probable or definite ALS diagnosis based on the El Escorial criteria, with a symptom duration of <2 years, age between 25 and 75years and with at least 70% forced vital capacity (FVC) will be treated for 6 months. The primary objective of the study is to evaluate the efficacy of CBME compared with placebo in slowing the disease progression measured by differences in mean ALS Functional Rating Scale-Revised and FVC score between the groups at the end of treatment. The secondary objectives are to evaluate the safety and tolerability of CBME by summarising adverse events, the effects of CBME on spasticity, pain, weight loss and quality of life assessed by the differences in mean Numeric Rating Scale for spasticity and Numeric Rating Scale for pain, percentage of total weight loss and ALS specific quality of life-Revised questionnaire.The study has been approved by the local Institutional Review Board. The results of this study will be published in a peer-reviewed journal.NCT03690791.

Data from controlled laboratory experiments in adults indicate that the subjective effects of cannabis vary by administration method (e.g., combustible, vaporized). Whether the subjective effects of cannabis experienced in the natural ecology and among adolescents differ by cannabis administration method is unknown. In this observational study, adolescents' retrospective reports of subjective effects after combustible, edible, and vaporized cannabis use were examined.Students from ten public schools in Los Angeles, CA, USA (M[SD] age = 16.1 [.43] years) who reported past 6-month use of combustible, edible, or vaporized cannabis (N = 584) were surveyed on subjective effects experienced after use (yes/no). They were provided with a 12 item self-report checklist of six positive (e.g., relaxed, energetic) and six negative (e.g., drowsy, lazy) subjective effects. For each method of administration, affirmative responses were summed in positive (range: 0-6) and negative (range: 0-6) effect composite scores.Generalized estimating equations adjusted for demographics and recent cannabis use revealed a graded pattern of differences in positive subjective effects across products, with highest scores for combustible (M[SD] = 3.98[1.76]), followed by edible (M[SD] = 3.58 [2.04]) and vaporized (M[SD] = 3.11 [2.21]) cannabis (all pairwise cross-product contrasts p < .01). Mean negative effect score was highest for edible (M[SD] = 2.27 [1.95]), followed by combustible (M[SD] = 1.94 [1.66]), and vaporized (M[SD] = 1.34 [1.73]) cannabis, respectively (all pairwise contrasts p < .02).Adolescents' reports of subjective effects varied across cannabis administration methods. Combustible cannabis' more desirable subjective effects profile might be indicative of higher abuse liability.

Genetic markers can be used in seeds and in plants to distinguish drug-type from fiber-type Cannabis Sativa L. varieties even at early stages, including pre-germination when cannabinoids are not accumulated yet. With this aim, this paper reports sequencing results for tetrahydrocannabinolic acid synthase (THCAS) and cannabidiolic acid synthase (CBDAS) genes from 21 C. sativa L. varieties. Taking into account that THCAS- and CBDAS-derived enzymes compete for the same substrate, the novelty of this work relies in the identification of markers based on both THCAS and CBDAS rather than THCAS alone. Notably, in our panel, we achieved an adequate degree of discrimination (AUC 100%) between drug-type and fiber-type cannabis samples. Our sequencing approach allowed identifying multiple genetic markers (single-nucleotide polymorphisms-SNPs-and a deletion/insertion) that effectively discriminate between the two subgroups of cannabis, namely fiber type vs. drug type. We identified four functional SNPs that are likely to induce decreased THCAS activity in the fiber-type cannabis plants. We also report the finding on a deletion in the CBDAS gene sequence that produces a truncated protein, possibly resulting in loss of function of the enzyme in the drug-type varieties. Chemical analyses for the actual concentration of cannabinoids confirmed the identification of drug-type rather than fiber-type genotypes. Genetic markers permit an early identification process for forensic applications while simplifying the procedures related to detection of therapeutic or industrial hemp.

The protective effect of cannabidiol (CBD), the non-psychoactive component of Cannabis sativa, against neuronal toxicity induced by cadmium chloride (CdCl2 10 μM) was investigated in a retinoic acid (RA)-differentiated SH-SY5Y neuroblastoma cell line. CBD (1 μM) was applied 24 h before and removed during cadmium (Cd) treatment. In differentiated neuronal cells, CBD significantly reduced the Cd-dependent decrease of cell viability, and the rapid reactive oxygen species (ROS) increase. CBD significantly prevented the endoplasmic reticulum (ER) stress (GRP78 increase) and the subcellular distribution of the cytochrome C, as well as the overexpression of the pro-apoptotic protein BAX. Immunocytochemical analysis as well as quantitative protein evaluation by western blotting revealed that CBD partially counteracted the depletion of the growth associated protein 43 (GAP43) and of the neuronal specific class III β-tubulin (β3 tubulin) induced by Cd treatment. These data showed that Cd-induced neuronal injury was ameliorated by CBD treatment and it was concluded that CBD may represent a potential option to protect neuronal cells from the detrimental effects of Cd toxicity.

Earlier this year we published a method article aimed at optimising protein extraction from mature buds of medicinal cannabis for trypsin-based shotgun proteomics (Vincent, D., et al. Molecules2019, 24, 659). We then developed a top-down proteomics (TDP) method (Vincent, D., et al. Proteomes2019, 7, 33). This follow-up study aims at optimising the digestion of medicinal cannabis proteins for identification purposes by bottom-up and middle-down proteomics (BUP and MDP). Four proteases, namely a mixture of trypsin/LysC, GluC, and chymotrypsin, which target different amino acids (AAs) and therefore are orthogonal and cleave proteins more or less frequently, were tested both on their own as well as sequentially or pooled, followed by nLC-MS/MS analyses of the peptide digests. Bovine serum albumin (BSA, 66 kDa) was used as a control of digestion efficiency. With this multiple protease strategy, BSA was reproducibly 97% sequenced, with peptides ranging from 0.7 to 6.4 kD containing 5 to 54 AA residues with 0 to 6 miscleavages. The proteome of mature apical buds from medicinal cannabis was explored more in depth with the identification of 27,123 peptides matching 494 unique accessions corresponding to 229 unique proteins from Cannabis sativa and close relatives, including 130 (57%) additional annotations when the list is compared to that of our previous BUP study (Vincent, D., et al. Molecules2019, 24, 659). Almost half of the medicinal cannabis proteins were identified with 100% sequence coverage, with peptides composed of 7 to 91 AA residues with up to 9 miscleavages and ranging from 0.6 to 10 kDa, thus falling into the MDP domain. Many post-translational modifications (PTMs) were identified, such as oxidation, phosphorylations, and N-terminus acetylations. This method will pave the way for deeper proteome exploration of the reproductive organs of medicinal cannabis, and therefore for molecular phenotyping within breeding programs.

Cannabis sativa L. is one of the most-studied species for its phytochemistry due to the abundance of secondary metabolites, including cannabinoids, terpenes and phenolic compounds. In the last decade, fiber-type hemp varieties have received interest for the production of many specialized secondary metabolites derived from the phenylpropanoid pathway. The interest in these molecules is due to their antioxidant activity. Since secondary metabolite synthesis occurs at a very low level in plants, the aim of this study was to develop a strategy to increase the production of such compounds and to elucidate the biochemical pathways involved. Therefore, cell suspensions of industrial hemp (C. sativa L. var. Futura) were produced, and an advantageous elicitation strategy (methyl jasmonate, MeJA) in combination with precursor feeding (tyrosine, Tyr) was developed. The activity and expression of phenylalanine ammonia-lyase (PAL) and tyrosine aminotransferase (TAT) increased upon treatment. Through 1H-NMR analyses, some aromatic compounds were identified, including, for the first time, 4-hydroxyphenylpyruvate (4-HPP) in addition to tyrosol. The 4-day MeJA+Tyr elicited samples showed a 51% increase in the in vitro assay (2,2-diphenyl-1-picrylhydrazyl, DPPH) radical scavenging activity relative to the control and a 80% increase in the cellular antioxidant activity estimated on an ex vivo model of human erythrocytes. Our results outline the active metabolic pathways and the antioxidant properties of hemp cell extracts under the effect of specific elicitors.

Illegal drug use is proposed to interfere with neurobiological functioning by damaging the neurotransmitter communication systems that are believed to be responsible for cognitive abilities, including perception, attention, and memory. This review specifically examined effects of illegal drug use on prospective memory (PM) - memory for future actions. Twenty- seven studies spanning 14 years were included in this review which were divided into two broad categories based on testing methods used: self-report and lab-based testing methods. The quality of the included studies was assessed across five categories: sample type, sample size, abstinence period, testing methods and control for confounding factors. The overall quality of evidence was good for six studies and moderate for sixteen studies and low for five studies. The results from the studies employing self-report were inconsistent as illegal drug users exhibited PM deficits in some studies, but not in others. However, the studies with lab-based testing methods demonstrated more consistent findings with illegal drug users scoring worse than non-users on various PM tests. There were also consistent findings on the link between the dosage of drug taken and level of PM deficit. Based on the literature, there is moderate evidence that illegal drug use impairs PM ability. We recommend that further lab-based studies be conducted to assess dose-response effects on drug-specificity.

Prompted by the ongoing debate regarding whether cannabis serves as a complement to or substitute for alcohol, this study uses prospective data to examine daily associations between medicinal versus recreational cannabis and alcohol use in veterans.Three semi-annual waves of Timeline Followback Interview data were collected from a sample of veterans who reported co-using alcohol and cannabis on at least one day (N = 115; 56% medicinal users; 93% male; 62,100 observations). Linear mixed effects models were used to examine the association between daily cannabis use and number of drinks consumed across time for both medicinal and recreational users and to examine the frequency medicinal cannabis used to substitute for alcohol.Compared to medicinal users, recreational users were more likely to drink more on cannabis use days relative to non-use days. Among medicinal users, those endorsing more frequent use of cannabis as a substitute for alcohol reported fewer number of drinks consumed on days when cannabis was used relative to non-use days.Among veterans, recreational users are at greater risk for increased drinking when co-using cannabis at the daily level, an association that is stable over time. Medicinal users may be at lower risk for increased drinking on days when cannabis is also used, especially those who endorse using cannabis to substitute for alcohol. Findings help clarify the debate on cannabis-alcohol substitution or complementary associations in a sample of veterans and suggests that alcohol interventions should address cannabis use as a risk factor, especially for recreational users.

Cannabis abuse commonly co-occurs with alcohol use disorder (AUD). With increased acceptance and accessibility to cannabis in the US, it is imperative to understand the psychological and neural mechanisms of concurrent alcohol and cannabis use. We hypothesized that neural alcohol-cue conditioning may extent to other drug-related stimuli, such as cannabis, and underwrite the loss of control over reward-driven behavior. Task-activated fMRI examined the neural correlates of alcohol- and cannabis-related word cues in 21 abstinent AUD and 18 control subjects. Relative to controls, AUD showed behavioral attentional biases and frontal hypoactivation to both alcohol- and cannabis-related words. This cue-elicited prefrontal hypoactivation was related to higher lifetime alcohol consumption (pcorrected < 0.02) and modulated by past cannabis use histories (p ≦ 0.001). In particular, frontal hypoactivation to both alcohol and cannabis cues was pronounced in AUD without prior cannabis exposure. Overall, frontal control mechanisms in abstinent AUD were not sufficiently engaged to override automatic alcohol and cannabis-related intrusions, enhancing the risk for relapse and potentially for alcohol and cannabis co-use with the increased social acceptance and accessibility in the US.

Use of cannabis to alleviate headache and migraine is relatively common, yet research on its effectiveness remains sparse. We sought to determine whether inhalation of cannabis decreases headache and migraine ratings as well as whether gender, type of cannabis (concentrate vs. flower), THC, CBD, or dose contribute to changes in these ratings. Finally, we explored evidence for tolerance to these effects. Archival data were obtained from StrainprintTM, a medical cannabis app that allows patients to track symptoms before and after using different strains and doses of cannabis. Latent change score models and multilevel models were used to analyze data from 12,293 sessions where cannabis was used to treat headache and 7,441 sessions where cannabis was used to treat migraine. There were significant reductions in headache and migraine ratings after cannabis use. Men reported larger reductions in headache than women and use of concentrates was associated with larger reductions in headache than flower. Further, there was evidence of tolerance to these effects. Perspective: Inhaled cannabis reduces self-reported headache and migraine severity by approximately 50%. However, its effectiveness appears to diminish across time and patients appear to use larger doses across time, suggesting tolerance to these effects may develop with continued use.

Cannabis is currently the most used illicit substance in the world with a global widespread distribution. Although its acute neurocognitive effects on human behaviour have been reported, there is a lack of robust analysis investigating the link, if any, between chronic cannabis use and neurocognitive function. A systematic review of the literature was conducted in order to identify relevant studies published from 2010 to 2019. A meta-analysis was performed on 13 selected studies testing performance of chronic cannabis users compared with non-users in six different neurocognitive domains. There was a low cross-sectional association between neurocognitive impairments and chronic cannabis use in cognitive impulsivity, cognitive flexibility, attention, short-term memory and long-term memory. No association was found between chronic cannabis use and motor impulsivity. By analysing a specific target population with strict inclusion criteria, these findings provide inconclusive evidence that there are cognitive impairments associated with chronic cannabis use. Future research is needed to determine if the findings of this meta-analysis are biased by the methodological limitations encountered.

The policies and practices related to medical cannabis are currently in flux. These changes have been associated with many controversies, and there is a lack of consensus within the medical community regarding medical cannabis practices.To validate clinical vignettes that can be used to examine and improve medical cannabis practices.Ten physicians participated in a Delphi survey of two consequent rounds in which they quantified the eligibility of medical cannabis therapy for six clinical vignettes describing both chronic pain and cancer patients.Higher consensus was achieved for the vignettes of cancer patients, which were additionally rated as more eligible for medical cannabis therapy. The highest level of consent (4.3 out of 5) was achieved regarding a vignette of a metastatic cancer patient. While in some cases physicians consolidated their ratings toward the group's average, in other cases they remained stable in their responses.While controversies related to medical cannabis are expected to remain rampant, the validated vignettes may facilitate assessment of clinical practices, which is essential for a successful implementation of medical cannabis policies. These vignettes may additionally be used in medical training for appropriate patient selection for medical cannabis authorization.

Depression is common among individuals with cannabis use disorder (CUD), particularly individuals who present to CUD treatment. Treatments that consider this comorbidity are essential.The goal of this secondary analysis was to examine whether N-acetylcysteine (NAC) reduced depressive symptoms among adults (age 18-50) with CUD (N = 302) and whether the effect of NAC on cannabis cessation varied as a result of baseline levels of depression. Bidirectional associations between cannabis use amount and depression were also examined.Data for this secondary analysis were from a National Drug Abuse Treatment Clinical Trials Network (NIDA CTN) multi-site clinical trial for CUD. Adults with CUD (N = 302) were randomized to receive 2400 mg of NAC daily or matched placebo for 12 weeks. All participants received abstinence-based contingency management. Cannabis quantity was measured by self-report, and weekly urinary cannabinoid levels (11-nor-9-carboxy-Δ9-tetrahydrocannabinol) confirmed abstinence. Depressive symptoms were measured by the Hospital Anxiety and Depression Scale.Depressive symptoms did not differ between the NAC and placebo groups during treatment. There was no significant interaction between treatment and baseline depression predicting cannabis abstinence during treatment. Higher baseline depression was associated with decreased abstinence throughout treatment and a significant gender interaction suggested that this may be particularly true for females. Cross-lagged panel models suggested that depressive symptoms preceded increased cannabis use amounts (in grams) during the subsequent month. The reverse pathway was not significant (i.e., greater cannabis use preceding depressive symptoms).Results from this study suggest that depression may be a risk factor for poor CUD treatment outcome and therefore should be addressed in the context of treatment. However, results do not support the use of NAC to concurrently treat co-occurring depressive symptoms and CUD in adults.Clinicaltrials.gov: NCT01675661.

Context: Chronic pain is highly prevalent in most of the industrialized nations around the world. Despite the documented adverse effects, opioids are widely used for pain management. Cannabinoids, and specifically Cannabidiol, is proposed as an opioid alternative, having comparable efficacy with better safety profile.Objectives: We aim to investigate the impact of full hemp extract cannabidiol (CBD) on opioid use and quality of life indicators among chronic pain patients.Methods: An initial sample of 131 patients was recruited from a private pain management center's investigative population. Ninety-seven patients completed the 8-week study. The primary inclusion criteria included patients between 30 and 65 years old with chronic pain who have been on opioids for at least 1 year. Data were collected at three different time points: baseline, 4, and 8 weeks. Opioid and other medication use were evaluated via the medication and psychiatric treatment receipt. Improvement was evaluated using four indices: Pain Disability Index (PDI-4); Pittsburgh Sleep Quality Index (PSQI), Pain Intensity and Interference (PEG); and Patient Health Questionnaire (PHQ-4).Results: Over half of chronic pain patients (53%) reduced or eliminated their opioids within 8 weeks after adding CBD-rich hemp extract to their regimens. Almost all CBD users (94%) reported quality of life improvements. The results indicated a significant relationship between CBD and PSQI (p = 0.003), and PEG (p = 0.006). There was a trend toward improvement but no significant relationship between CBD use and PHQ and PDI.Conclusion: CBD could significantly reduce opioid use and improve chronic pain and sleep quality among patients who are currently using opioids for pain management.Key Message: This is a prospective, single-arm cohort study for the potential role of cannabinoids as an alternative for opioids. The results indicate that using the CBD-rich extract enabled our patients to reduce or eliminate opioids with significant improvement in their quality of life indices.

Background: There is an increasing focus among cancer patients on the use of cannabis-based medicine (CBM) as a supplement to conventional palliative care. However, physicians are reluctant to engage in dialog with the patients as clinical evidence is lacking. As a result, the patients are often left alone to rely on their own judgment in purchasing CBM products on the illegal market. Objective: Our study aimed to collect information from CBM treatment-experienced cancer patients receiving palliative care regarding treatment decision rationale and outcome. Design: A qualitative interview study using thematic analysis was performed. Setting/Participants: A total of 20 informants took part in individual interviews. Results: To the question addressing the main rationale for starting CBM treatment, all 20 patients responded that they carried a hope that cannabis would have a curative effect on the cancer disease. Most patients reported relief of symptoms, such as insomnia, anxiety, nausea, and pain, after initiation of CBM treatment, but this outcome was perceived as less of a focus in comparison to hope of a cure. Conclusion: This study contributes with knowledge from the perspective of the cancer patient in palliative care regarding the decision behind the use of CBM. There seems to be striving for surviving cancer based on the rationale that cannabis may constitute curative properties. Relief of symptoms is perceived as a secondary reason for treatment. This knowledge is essential in the dialog between the health professional and the cancer patient about the use of CBM products for treatment.

During the past decade, the ability of surface-enhanced Raman spectroscopy (SERS) to measure extremely low concentrations, such as mg/L and below, and the availability of hand-held Raman spectrometers, has led to a significant growth in the number and variety of applications of SERS to real-world problems. Most of these applications involve the measurement of drugs, such as quantifying medication in patients, identifying illicit drugs in impaired drivers, and more recently, identifying drugs used as weapons. Similar to Raman spectroscopy, most of the point-of-care and field applications involve the identification of the drug to determine the course of action. However, unlike Raman spectroscopy, spectral libraries are not readily available to perform the necessary identification. In a large part, this is due to the uniqueness of the commercially available SERS substrates, each of which can produce different spectra for the same drug. In an effort to overcome this limitation, we have measured numerous drugs using the most common, and readily available SERS material and hand-held Raman analyzers, specifically gold colloids and analyzers using 785 nm laser excitation. Here we present the spectra of some 39 drugs of current interest, such as buprenorphine, delta-9 tetrahydrocannabinol, and fentanyl, which we hope will aid in the development of current and future SERS drug analysis applications.

Hemp (Cannabis sativa L.) is a multifunctional crop that is capable of prompt environmental adaptation. In this study, a monoecious cultivar (Futura 75) and a dioecious one (Finola) were tested in a mountain area in Valsaviore (Rhaetian Alps, Italy; elevation: 1,100 m a.s.l.) during the growing season 2018. Phytochemical behavior was evaluated by different analytical approaches: HPLC-high-resolution mass spectrometry, SDS-PAGE LC-MS/MS, HS-SPME GC-MS, and GC-FID in order to obtain complete profile of two varieties cultivated in altitude. CSR functional strategy used for ecological evaluation revealed that both genotypes are mainly competitors, although Finola is more stress tolerator (C:S:R = 57:26:17%) than Futura (C:S:R = 69:15:16%). The Finola inflorescences were characterized by higher quantities of β-ocimene and α-terpinolene, while α- and ß-pinene accompanied by extremely high ß-myrcene were found as predominant in Futura. Both varieties were rich in sesquiterpenes (45 recognized) among which trans-caryophyllene and α-humulene were the most abundant. Total tetrahydrocannabinol level was lower than 0.1%, while the most abundant cannabinoid was cannabidiolic acid (CBDA): 2.3% found in Finola vs. 2.7% revealed for Futura. The level of corresponding neutral form, cannabidiol, varied drastically: 0.27% (Finola) vs. 0.056% (Futura). Finola showed the unique cannabinoid profile with unexpectedly high cannabidivarin, 2-fold higher that corresponding acidic analogue, whereas the particularity of Futura 75 was the occurrence of cannabigerolic acid (CBGA) in the quantities that was double than those exposed for Finola. The seeds from both chemovars proved to be rich in polyunsaturated fatty acids, and Finola showed a higher ratio ω6/ω3. No difference was found in the protein content, and the SDS-PAGE profile was similar. The most abundant protein was edestin, followed by heat shock protein 70, ß-conglycinin, and vicilin. In conclusion, comprehensive phytochemical and ecological study of two fiber-type varieties cultivated in Italian Alps displayed specific, legal, and safe cannabinoids profile, followed by particular terpene composition, polyunsaturated fatty acids content, and favorable protein profile. This postulates that geographical provenience of hemp should be considered in selecting a variety that would be suitable for a specific end-use nutraceutical application.

The objective of this study was to examine adolescents' self-reported exposure to cannabis marketing in states with legalized cannabis and its association with past-year cannabis use.We conducted a cross-sectional, online panel survey of 469 adolescents aged 15-19 years residing in four states with legal retail cannabis for adult use. Adolescents self-reported exposure to cannabis marketing on social or traditional media (i.e., outdoor or print) and past-year cannabis use. Logistic regression generated estimated odds of youths' past-year cannabis use by marketing exposure after adjusting for demographic factors and cannabis-related social norms.Exposure to cannabis marketing on Facebook, Twitter, and Instagram was associated with increased odds of past-year cannabis use of 96% (95% confidence interval [CI]: 15%-234%), 88% (95% CI: 11%-219%), and 129% (95% CI: 32%-287%), respectively. Odds of past-year cannabis use increased by 48% (95% CI: 16%-87%) with each additional social media platform where adolescents reported exposure.Despite restrictions that prohibit cannabis advertising on social media, adolescents are exposed to cannabis marketing via social media, and this exposure is associated with recent cannabis use. States should consider further regulation of cannabis marketing on social media.

The United States has witnessed enormous changes concerning the acceptance of medicinal and recreational cannabis use. Sixty-three percent of the US population has access to medicinal cannabis markets, which offer increasingly diverse and potent cannabis products. Considering the rapidly changing cultural, political, and legal landscape, the scientific literature does not adequately inform public policy, medical decision making, or harm reduction approaches. The goals of this paper are to (1) investigate the state of cannabis research on medical conditions commonly treated with cannabis, (2) review the barriers that have led to large gaps between cannabis use and available empirical data, and (3) suggest a path forward with new research designs to address these gaps. Thus, we aim to advance a more nuanced understanding of the barriers to cannabis research and suggest innovative research designs necessary for rapid development of a meaningful knowledge base.

The rapidly changing landscape of cannabis in terms of availability, potency, and routes of administration, as well as the decrease in risk perception and changing norms, have contributed to an increase in the popularity of cannabis. Cannabis use is associated with a poorer recovery from a psychotic disorder, increasing the risk of relapse, rehospitalization, and lower social functioning. Data are mixed regarding cannabis use as a component cause of psychosis in people at risk for psychotic disorder. Care providers, parents, and schools must educate youth and adolescents about the risks of cannabis use.

Youth experiencing psychosis also frequently misuse substances, making it clinically challenging to differentiate substance-induced psychosis (SIP) from a primary psychotic disorder (PPD), which has important implications for management and prognosis. This article presents practical considerations related to differentiating SIP from PPD, including information on substances associated with symptoms of psychosis. Recommendations for management of SIP are also reviewed, including screening for and treating comorbid substance use disorders and using evidence-based medication and psychosocial interventions.

Background and Purpose- Amidst legalization of therapeutic and recreational use of marijuana/cannabis in the United States, cerebrovascular effects of marijuana use remain largely unknown, especially among young adults. We aimed to examine the association between marijuana use (18-44 years) among young adults and stroke events. Methods- The study analyzed pooled data from the Behavioral Risk Factor Surveillance System (2016-2017)-a nationally representative cross-sectional survey collected by the Centers for Disease Control and Prevention. Weighted logistic regression models were used to examine an association of recent marijuana use (within the last 30 days) and stroke in young adults (18-44 years) adjusting for patient demographics, risk behavior, and relevant comorbidities. Results- Overall, 13.6% of participants (n=43 860; weighted 35.5 million; 49.9% men) reported using marijuana recently (in the last month), with 63.3% of them being men. Compared with nonusers, marijuana users were often younger (18-34 years; 73.8% versus 61%), non-Hispanic white or black, and with some college education. Marijuana users were often physically active (81.8% versus 77.5%), heavy drinkers (16.8% versus 4.9%), current combustible cigarette users (37.9% versus 15%) and had lower prevalence of hypertension, diabetes mellitus, and hyperlipidemia as compared with nonusers (P<0.01). Young adults with recent marijuana use showed 1.82× higher odds (adjusted odds ratio, 1.82 [95% CI, 1.08-3.10]) of stroke compared with nonusers, which further increased to 2.45× higher (adjusted odds ratio, 2.45 [95% CI, 1.31-4.60]) among frequent marijuana users (>10 days/month). Compared with nonusers, stroke odds were even higher among frequent marijuana users with concomitant combustible cigarette use (adjusted odds ratio, 3.12 [95% CI, 1.40-6.97]) and e-cigarette use (adjusted odds ratio, 2.63 [95% CI, 1.07-6.46]), respectively. Conclusions- There may be a significantly higher odds of stroke in young marijuana users (18-44 years) as compared with nonusers with even greater odds among frequent users (>10 days/month).

Cannabis legalization and use are increasing globally, however, little is known about associations between cannabis use and other health behaviors, such as physical activity (PA). Importantly, the extent to which cannabis use is associated with PA in adolescents is yet to be explored in low- and middle-income countries (LMICs), where there may be unique sociodemographic and environmental characteristics compared with high-income countries. Therefore, this study examined the association between PA and cannabis use among adolescents in 21 LMICs using data from the 2010-2016 Global School-based Student Health Survey.A multivariable logistic regression analysis was performed among a final sample of 89,777 adolescents (49.2% females) aged 12-15 years with a mean (SD) age of 13.7 (0.9) years.The overall prevalence of past (i.e., in lifetime but not in past 30 days) and current (in past 30 days) cannabis use were 1.0% and 2.9% respectively, while the prevalence of adequate PA in the past week (7 days/week of 60 min of PA) was 16.6%. The prevalence of adequate levels of PA in past and current cannabis use was 7.3% and 6.9%, respectively. Current and past cannabis use (vs. never) were associated with a significant 0.62 (95% CI = 0.41-0.94) and 0.43 (95%CI = 0.30-0.63) times lower odds for achieving adequate levels of PA, respectively.The results underscore the high prevalence of low PA among adolescents in LMICs, and emphasize the need to understand behavioral factors that may affect PA levels, such as cannabis use, when designing interventions to improve health.

Research on adolescent heroin use has focused on national surveillance, access, prevalence of use, and overdose deaths, however, to our knowledge, no study has examined local-level differences in the prevalence of adolescent heroin use in the context of nonmedical prescription opioid (NMPO) use. This study characterizes heroin and NMPO use among US high school students in select urban areas by sex and race/ethnicity.Data are from 21 urban school districts that participate in CDC's Local Youth Risk Behavior Surveillance System. We describe 2017 prevalence estimates (and 95 % confidence intervals) of lifetime heroin and NMPO use among youth stratified by sex and race/ethnicity (i.e., White, Black, Hispanic/Latino).The highest estimates of heroin use were in Baltimore, MD (7.6 %), Shelby County, TN (6.3 %), and Duval County, FL (6.1 %), whereas NMPO use was highest in Duval County, FL (18.1 %), Cleveland, OH (18.0 %), and Shelby County, TN (16.8 %). Heroin use was higher among boys than girls, especially among Hispanic/Latino boys in Duval County (12.3 %) and Black boys in Baltimore (10.9 %). NMPO use was highest among Hispanic/Latino girls (21.3 %) and White girls (19.9 %) in Duval County.While some cities and subpopulations with high levels of adolescent heroin use also had elevated levels of NMPO use, others did not, illustrating the complexities of this opioid epidemic.

Rural-urban differences in cigarette and cannabis use have traditionally shown higher levels of cigarette smoking in rural areas and of cannabis use in urban areas. To assess for changes in this pattern of use, we examined trends and prevalence of cigarette, cannabis, and co-use across urban-rural localities.Urban-rural trends in current cigarette and/or cannabis use was evaluated using 11 cohorts (2007-2017) of the National Survey on Drug Use and Health (NSDUH; N = 397,542). We used logistic regressions to model cigarette and cannabis use over time, adjusting for demographics (age, gender, race/ethnicity, income, education), in addition to assessing patterns of cannabis use among cigarette smokers and nonsmokers.Despite decreases in cigarette smoking overall, between 2007 and 2017, the urban-rural disparity in cigarette smoking increased (AOR = 1.17), with less reduction in rural as compared to urban cigarette smokers. Cannabis use increased in general (AOR = 1.88 by 2017), with greater odds in urban than rural regions. Cannabis use increased more rapidly in non-cigarette smokers than smokers (AOR = 1.37 by 2017), with 219% greater odds of cannabis use in rural non-cigarette smokers in 2017 versus 2007.Rurality remains an important risk factor for cigarette smoking in adults and the fastest-growing group of cannabis users is rural non-cigarette smokers; however, cannabis use is currently still more prevalent in urban areas. Improved reach and access to empirically-supported prevention and treatment, especially in rural areas, along with dissemination and enforcement of policy-level regulations, may mitigate disparities in cigarette use and slow the increase in rural cannabis use.

Adolescence is the transitional period between childhood and adulthood, during which extensive brain development occurs. Since this period also overlaps with the initiation of drug use, it is important to consider how substance use during this time might produce long-term neurobiological alterations, especially against the backdrop of developmental changes in neurotransmission. Alcohol, cannabis, nicotine, and opioids all produce marked changes in the expression and function of the neurotransmitter and receptor systems with which they interact. These acute and chronic alterations also contribute to behavioral consequences ranging from increased addiction risk to cognitive or neuropsychiatric behavioral dysfunctions. The current review provides an in-depth overview and update of the developmental changes in neurotransmission during adolescence, as well as the impact of drug exposure during this neurodevelopmental window. While most of these factors have been studied in animal models, which are the focus of this review, future longitudinal studies in humans that assess neural function and behavior will help to confirm pre-clinical findings. Furthermore, the neural changes induced by each drug should also be considered in the context of other contributing factors, such as sex. Further understanding of these consequences can help in the identification of novel approaches for preventing and reversing the neurobiological effects of adolescent substance use.

Medicinal cannabis has remarkable therapeutic potential, but its clinical use is limited by the psychotropic activity of Δ9-tetrahydrocannabinol (Δ9-THC). However, the biological profile of the carboxylated, non-narcotic native precursor of Δ9-THC, the Δ9-THC acid A (Δ9-THCA-A), remains largely unexplored. Here we present evidence that Δ9-THCA-A is a partial and selective PPARγ modulator, endowed with lower adipogenic activity than the full PPARγ agonist rosiglitazone (RGZ) and enhanced osteoblastogenic effects in hMSC. Docking and in vitro functional assays indicated that Δ9-THCA-A binds to and activates PPARγ by acting at both the canonical and the alternative sites of the ligand-binding domain. Transcriptomic signatures in iWAT from mice treated with Δ9-THCA-A confirmed its mode of action through PPARγ. Administration of Δ9-THCA-A in a mouse model of HFD-induced obesity significantly reduced fat mass and body weight gain, markedly ameliorating glucose intolerance and insulin resistance, and largely preventing liver steatosis, adipogenesis and macrophage infiltration in fat tissues. Additionally, immunohistochemistry, transcriptomic, and plasma biomarker analyses showed that treatment with Δ9-THCA-A caused browning of iWAT and displayed potent anti-inflammatory actions in HFD mice. Our data validate the potential of Δ9-THCA-A as a low adipogenic PPARγ agonist, capable of substantially improving the symptoms of obesity-associated metabolic syndrome and inflammation.

Cannabis sativa was introduced in Latin America in the 16th century. Nevertheless, many years have elapsed, and scientific progress and the medicinal use of C sativa have been restricted by the national laws of the countries in the region.In Argentina, the first law on medical cannabis, approved in 2017 (#17,350), establishes a regulatory framework for the medical use and scientific research of this plant and its derivatives. In 2018, the first clinical research protocol in Latin America was approved at Hospital de Pediatria Garrahan (Buenos Aires, Argentina) to evaluate the efficacy and safety of cannabidiol (CBD) oil for the treatment of pediatric patients with refractory epilepsy. In this context, the role of pharmacists in the health care system related to the study protocol and the medicinal use of CBD has evolved from dispensing to active participation in clinical follow-up and research protocols.Considering this experience, here we discuss the active role of the clinical pharmacist in the use of medicinal cannabis. Medicinal cannabis should be controlled in a legal framework based on clinical evidence, and the participation of the pharmacist in research and clinical protocols, as well as the dispensing and provision of information on the medicinal products should be emphasized in the clinical setting.

Polysubstance use (PSU) is associated with worse prognosis and poorer physical and mental health compared to single substance use. The current study provides information about PSU patterns by examining a diverse range of alcohol/substance use behaviors ranging from low-level experimentation to indicators of severe abuse. In addition, the current study, for the first time, examines how simultaneous co-use of multiple substances cluster with other more commonly studied PSU behaviors.Latent Class Analysis was used to identify patterns of substance use, in a sample of young-adults (n = 2098), using 25 items from the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA-II) including: items assessing severity of problems with alcohol, cannabis, stimulants, opiates, and sedatives; items assessing # of lifetime uses; items assessing simultaneous co-use of all combinations of substances. Then the association of class membership and age, antisocial and impulsive personality, experience seeking, anxiety, and neuroticism was examined using Multinomial Regression.Fit indices (i.e. AIC, SSABIC, and entropy) and interpretability of classes supported a five-class solution: "Low Problems" (32% of sample), "Alcohol Primary" (11%), "Alcohol and Cannabis" (25%), "Moderate PSU" (23%), and "Severe PSU" (9%). Simultaneous co-use behaviors discriminated between lower and higher severity groups. Externalizing personality constructs robustly predicted membership in the "Moderate" and "Severe" PSU classes compared to the "Alcohol Primary" class.PSU patterns followed an additive pattern of use with lower severity classes using alcohol/cannabis and more severe classes using other illicit substances in addition. Co-use items provided valuable information about PSU severity.

Young adults in the U.S. report high levels of stress which are known to contribute to depression and anxiety. Regular cannabis users frequently cite coping with stress as their primary motivation for use. However, research indicates that coping motives are associated with potentially negative outcomes, including cannabis-related problems and negative affect. Therefore, the theoretical rationale for the present study is that using cannabis to cope with stress may be maladaptive as it may exacerbate the same problems users are trying to ameliorate. That is, using cannabis to cope may potentiate links between stress and negative affect. We therefore sought to investigate whether cannabis use motives moderate the associations between stress and negative affect. A sample of 988 cannabis using college students completed an anonymous online survey containing measures of cannabis use, cannabis use motives, stress, depression, and anxiety. Correlation analyses revealed significant positive relationships between these variables. Moderation analyses indicated that coping motives was a significant moderator of the relationship between stress and depression, controlling for anxiety. In contrast, expansion and conformity motives were significant moderators of the relationship between stress and anxiety, controlling for depression. While cannabis may provide temporary relief from symptoms of stress, depression, and anxiety, using cannabis to cope may be related to higher levels of depression, and use of cannabis for expansion and conformity may be related to higher levels of anxiety. These findings have practical implications and contribute to emerging evidence demonstrating that motives for cannabis use may predict differential mental health outcomes.

Mortality and morbidity rates related to prescription opioid analgesics have been rising in North America and may be a gateway to the nonmedical use of prescription opioids (NUPO). The purpose of this study was to explore correlates of NUPO in the adolescent population given the scarce literature in this area.Cross-sectional data from 10,163 middle- and high-school students (15.1 ± 1.8 years old; 57.0% female; 55.6% White ethnic background) in Ontario were derived from the 2017 Ontario Student Drug Use and Health Survey. Potential correlates of NUPO in the past year included sociodemographic, behavioral, parental, and school characteristics.Overall prevalence of NUPO was 10.7%. In the final multivariable model, NUPO was significantly associated with 8 of the 21 correlates examined. Students who used prescription opioids nonmedically were of black, South Asian, and "other" ethnic backgrounds (OR 2.83, OR 1.77, and OR 1.67, respectively); reported a lower subjective socioeconomic status (OR 0.92), lower parental support (OR 0.90), and lower academic performance (OR 0.86); met physical activity recommendations (OR 1.48); consumed energy drinks (OR 1.42); smoked tobacco cigarettes (OR 2.33); and used cannabis (OR 1.84).Findings from this study show a wide variety of correlates of NUPO among Canadian adolescents, and highlight the need for further research and the value in targeted prevention and multi-level intervention programs for NUPO in this population.

To summarize evidence on the frequency and predictors of health-care utilization among people who use illicit drugs.Systematic search of MEDLINE, EMBASE and PsychINFO for observational studies reporting health-care utilization published between 1 January 2000 and 3 December 2018. We conducted narrative synthesis and meta-analysis following a registered protocol (identifier: CRD42017076525).People who use heroin, powder cocaine, crack cocaine, methamphetamine, amphetamine, ecstasy/3,4-methyl​enedioxy​methamphetamine (MDMA), cannabis, hallucinogens or novel psychoactive substances; have a diagnosis of 'substance use disorder'; or use drug treatment services.Primary outcomes were the cumulative incidence (risk) and rate of care episodes in three settings: primary care, hospital admissions (in-patient) and emergency department (ED).Ninety-two studies were included, 84% from North America and Australia. Most studies focused on people using heroin, methamphetamine or crack cocaine, or who had a diagnosis of drug dependence. We were able to conduct a meta-analysis of rates across 25 studies reporting ED episodes and 25 reporting hospital admissions, finding pooled rates of 151 [95% confidence interval (CI) = 114-201] and 41 (95% CI = 30-57) per 100 person-years, respectively; on average 4.8 and 7.1 times more often than the general population. Heterogeneity was very high and was not explained by drugs used, country of study, recruitment setting or demographic characteristics. Predictors of health-care utilization were consistent across studies and included unstable housing, drug injection and mental health problems. Opioid substitution therapy was consistently associated with reduced ED presentation and hospital admission. There was minimal research on health-care utilization by people using ecstasy/MDMA, powder cocaine, hallucinogens or novel psychoactive substances.People who use illicit drugs are admitted to emergency department or hospital several times more often than the general population.

Given the increased availability of tobacco products and devices, rising trends of vaping, and changing marijuana policies in the United States (U.S.), this study reports the prevalence of U.S. young adults using tobacco products/devices for marijuana consumption and associations with substance use problems.U.S. nationally representative data from Wave 3 (2015-2016) of the Population Assessment of Tobacco and Health Study were used to assess young adults' (18-24 years old, unweighted sample = 8453) ever marijuana use and ever use of electronic nicotine delivery systems (ENDS), hookah, or cigars for marijuana consumption. A multinomial logistic regression predicted the Substance Use Problem subscale of the Global Appraisal of Individual Needs inventory categorized into low (0-1), moderate (2-3) and high (4 or more) symptoms.Weighted analyses indicated about half of young adults (52.1%) had ever used marijuana. Of this group, the majority (80.1%) ever used any tobacco product/device for marijuana use including: ENDS (24.5%), hookah (25.2%), or cigar (74.0%). Ever use of tobacco products/devices for marijuana significantly predicted moderate (RRR = 1.70, p < 0.01) and high (RRR = 4.67, p < 0.01) substance use problems controlling for sex, race, employment, education, and past 30-day cigarette, cigar, ENDS, hookah, marijuana and alcohol use.Use of tobacco products/devices for marijuana consumption is common among U.S. young adults and it is associated with substance use problems. A better understanding of how tobacco devices are being used to support use of both substances and the outcomes of co-use are needed to inform policy and public health interventions.

Rates of marijuana legalization have increased rapidly in recent years resulting in the marketing of alternative products like edibles that do not involve inhaling smoke. Edibles however pose unique public health challenges due to their greater risk for over-intoxication.1858 young adults were surveyed every six months from 2016 to 2018. Logistic regression models examined trends in use and perceptions of harm. Chi-squared tests compared demographic and behavioral characteristics of edible users and non-users by frequency of marijuana use.Perceptions of no harm from edibles increased (25.4%, 27.3%, 26.7%, 28.4%, 29.6%; p = 0.006) while it declined for smoking marijuana (12.2%, 13.5%, 11.7%, 10.6%, 9.1%; p < 0.001). Among non-daily marijuana users, edible use increased (20.3%, 24.8%, 30.5%, 36.2%, 36.6%; p < 0.001) while smoking marijuana declined for both daily and non-daily users. Among daily users, edible users were more likely to use all modes of consumption than non-edible users. Among non-daily users, edible users were less likely to smoke marijuana and perceive harm from edibles and were more likely to perceive harm from smoking marijuana and have visited a dispensary than non-edible users.Edibles are increasingly consumed and perceived to not be harmful, despite the greater danger of over-intoxication. However, daily use of edibles alone is uncommon. The finding that edible users were more likely to have visited a dispensary provides a potential intervention point for consumer education. Strong scientific evidence is needed to guide policymakers in best practices for communicating knowledge and potential harms of these products.

Polydrug use among adolescence is a widespread phenomenon and has increased in the last few years. In particular, most nandrolone decanoate (Nan) abusers combine its use with cannabis (Can); thus, studying the consequences of this combination in adolescent subjects is important because potentiation of their effects may increase their neurotoxicity. The present study was designed to study the neurotoxic effects of Nan and Can, alone and in combination, in adolescent male rats by studying the behavioural, biochemical, and histopathological effects. Nan (15 mg/kg, s.c.) and Can (20 mg/kg, s.c.) were given alone or in combination to rats once daily for one month. The combined administration of Can and Nan induced learning and spatial memory deficits, hypo-locomotion, anxiety and aggression in adolescent rats as evidenced by the Morris water maze, open field, elevated plus maze, and defensive aggression tests. In parallel, rats treated with the combination showed severe deleterious effects in the hippocampal and prefrontal cortex (PFC) neural architecture along with a decrease in brain-derived neurotropic factor. Furthermore, combined administration of Can and Nan increased oxidative stress (significantly increased malondialdehyde and nitric oxide levels and reduced glutathione content), elevated brain pro-inflammatory cytokines (tumour necrosis factor alpha and interleukin 1 beta), and upregulated caspase-3, caspase-8, and caspase-9 mRNA expression and cytochrome c levels. In conclusion, abuse of both Can and Nan conferred greater neurotoxic effects than either drug alone that were at least partially attributed to oxidative stress, inflammation, and intrinsic and extrinsic apoptosis in the hippocampus and PFC of rats.

Medical students are thought to have increased pressures in study life beyond that of their peers. This could impact their psychological wellbeing, burnout and substance use, impeding a smooth transition into the health workforce. A cross-sectional electronic survey of one of New Zealand's two medical schools was undertaken, and students in all years were invited to participate through email. Two hundred and twenty students completed the survey. Forty-six students (21%) reported that they were currently seeing a GP or Allied Healthcare Professional (AHP) for their mental ill-health. Seventy-seven students (35%) reported having taken cannabis during medical school. The number of respondents reaching the threshold for CAGE, and thus demonstrating problem drinking, was 40 (18%). Additionally, burnout levels were scored, with 150 students (68%) classifying as disengaged and 169 (77%) as suffering from exhaustion on the Oldenburg burnout measure. Going forwards, organizational bodies including governments and medical schools should place emphasis on the importance of optimizing medical student wellbeing, including resilience training and improved workforce wellbeing planning, to positively impact not just medical students as they progress to doctors, but for patients, and the healthcare system as a whole.

Objective To study the trends of arrhythmia hospitalizations with cannabis use disorders (CUDs) in terms of demographic characteristics and inpatient outcomes. Methods We used the nationwide inpatient sample (NIS) data during the post-legalization period (2010-2014) and included 570,556 arrhythmia inpatients (age, 15-54 years), and 14,426 inpatients had comorbid CUD (2.53%). We used the linear-by-linear association test and independent-sample T-test for assessing the change in hospital outcomes in inpatients with CUD. Results Arrhythmia hospitalizations with CUD increased by 31% (2010-2014). This increasing trend was seen in adults (45-54 years, P < 0.001) and was predominant in males (77.6%). Hypertension (40.6%), hyperlipidemia (17.6%), and obesity (15%) were prevalent medical comorbidities with variable trends over the five years. Among substance use disorders, tobacco (50.9%), and alcohol (31.4%) were major comorbidities with a variable trend (P = 0.003 for each). There was a 71.4% increase in the inpatient mortality rate between 2010 (0.7%) and 2014 (1.2%). The mean length of stay was three days, and the total hospitalization charges have been increasing (P < 0.001), averaging $35,812 per hospital admission. Conclusion Chronic cannabis use or abuse worsens hospitalization outcomes in arrhythmic patients, and more clinical studies are needed to study the causal association between these conditions due to the rising mortality risk.

The hemp plant (Cannabis sativa L.) has a long tradition of being used for many different purposes such as industry, medicine and nutrition. In particular, because hemp seed (HS) is rich in oil protein and considerable amounts of dietary fiber, vitamins and minerals that are particularly suitable also for animal nutrition. Different studies have evaluated HS on qualitative and quantitative properties of livestock products but as of today, nobody has investigated the molecular pathway behind HS supplementation in farm animals. Thus, in this study, we will report the first RNA sequencing of the whole-blood transcriptome of ewes fed either with a controlled diet (CTR, n = 5) or with a diet supplemented with 5% of hemp seed (HSG, n = 5). Applying a false discovery rate (FDR) <0.05 and a log2FC either higher than 0.5 or lower than -0.5, we identified 314 differentially regulated genes in the HS-supplemented group compared to the CTR group. Several genes encoding for different subunits belonging to the complex I, II, III, IV and ATP-synthase were up-regulated making oxidative phosphorylation (FDR: 3.05e-19) and thermogenesis (FDR: 2.17e-16) the highest up-regulated pathways in our study. Moreover, we found up-regulation in different genes involved in lactose biosyntheses such as GALK1 and PGM1 and, as a result, we observed a statistically higher lactose percentage in the HSG group (p < 0.05). These results indicate that HS supplementation positively affects the energy production pathway in lactating ewes conferring them also more resistance to adverse climatic conditions such as low temperature. Finally, the higher milk lactose content makes the derived dairy products more profitable.

According to recent studies, Cannabidiol (CBD), one of the main components of Cannabis sativa, has anticancer effects in several cancers. However, the exact mechanism of CBD action is not currently understood. Here, CBD promoted cell death in gastric cancer. We suggest that CBD induced apoptosis by suppressing X-linked inhibitor apoptosis (XIAP), a member of the IAP protein family. CBD reduced XIAP protein levels while increasing ubiquitination of XIAP. The expression of Smac, a known inhibitor of XIAP, was found to be elevated during CBD treatment. Moreover, CBD treatment increased the interaction between XIAP and Smac by increasing Smac release from mitochondria to the cytosol. CBD has also been shown to affect mitochondrial dysfunction. Taken together, these results suggest that CBD may have potential as a new therapeutic target in gastric cancer.

Cannabis use disorder (CUD) prevalence among people reporting past-year cannabis use declined from 2002-2016. We examined whether similar reductions in CUD were observed among people reporting daily/almost daily cannabis use. We expected that CUD prevalence among people reporting daily/almost daily use would not decrease.We used 2002-2016 National Survey on Drug Use and Health (NSDUH) data, including 22,651 individuals using cannabis 300+ days in the past year. CUD was defined using DSM-IV criteria for cannabis abuse and/or dependence. Age categories included: 12-17, 18-25, and 26 + . Annual prevalence of CUD, cannabis dependence, cannabis abuse, and each individual abuse/dependence items accounted for the complex survey design. Differences in trends over time were examined by age group.From 2002-2016, the prevalence of CUD among people reporting daily/almost daily cannabis use decreased by 26.8% in adolescents, by 29.7% in ages 18-25, and by 37.5% in ages 26 + . Prevalence of DSM-IV cannabis dependence decreased significantly among adolescents (-43.9%) and young adults (-26.8%) but remained stable in adults 26 + . Reductions in most dependence items were observed in young adults, with less consistent patterns in adolescents and adults 26 + . Prevalence of DSM-IV cannabis abuse decreased overall and for each abuse item across all age groups.Contrary to expectations, CUD prevalence decreased significantly across all ages reporting daily/almost daily cannabis use between 2002-2016. Cannabis dependence prevalence decreased for adolescents and young adults and was stable only among adults ages 26+ reporting daily/almost daily cannabis use. Potential drivers of this decrease should be further explored.

Persons dually diagnosed with opioid and cocaine dependence (OD + CD) present a clinical challenge and are at risk of morbidity and mortality. The time of escalation of heroin and cocaine exposure in persons with OD + CD remain understudied, and the influence of gender and other variables have not been examined. This observational study focused on the time of escalation of heroin and cocaine in volunteers with OD + CD, examining gender and exposure to other drugs (e.g., cannabis or alcohol) as predictors. Ages of first use and of onset of heaviest use of each drug were collected (in whole years). Time of escalation was defined as the interval between age of first use and onset of heaviest use.sequentially ascertained adult volunteers recruited from the New York Metropolitan area, of which n = 297 were diagnosed with OD + CD.Instruments administered were the SCID-I diagnostic interview (DSM-IV criteria), BIS-11 impulsiveness scale, and KMSK scales, dimensional measures of maximal exposure to specific drugs.In volunteers with OD + CD, ages of onset of heaviest use of cannabis (median age = 15) and alcohol (median age = 19) were in adolescence or emerging adulthood and preceded those for heroin and cocaine (median ages = 26 and 25, respectively). Maximal levels of cannabis and alcohol exposure were high, in volunteers with OD + CD. In adjusted Cox regressions, gender was not a significant predictor of time of heroin or cocaine escalation. However, more rapid time of alcohol escalation was a predictor of more rapid time of escalation of both heroin and cocaine, in volunteers with OD + CD.

Limited evidence suggests that early cannabis use is associated with sleep problems. Research is needed to understand the developmental impact of early regular cannabis use on later adult sleep duration.In a sample of 1656 adult twins (56% female, Mean age = 25.79yrs), linear mixed effects models were used to analyze the influence of retrospectively assessed age of onset of regular cannabis use on adult sleep duration controlling for sex, depression, and current substance use. Twin analyses provided genetic and environmental variance estimates as well as insights into the association and potential casual relationships between these traits.Earlier age of onset for regular cannabis use was significantly associated with shorter adult sleep duration on both weekdays (β = -0.13, 95% CI = [-0.23, -0.04]) and weekends (β = -0.18, 95% CI = [-0.27, -0.08]). Additive genetics significantly contributed to the onset of regular cannabis use (a2 = 76%, 95% CI = [68, 85]) and adult weekend sleep duration (a2 = 20%, 95% CI = [11, 32]). We found evidence of a significant genetic correlation (rA = -0.31, 95% CI = [-0.41, -0.15]) between these two traits and our best fitting model was consistent with early onset of regular cannabis use causing shorter adult weekend sleep duration (β = -0.11, 95% CI = [-0.18, -0.03]).Our results are consistent with the hypothesis that early onset of regular cannabis use may have a negative impact on adult sleep duration.

Government monopolies of markets in hazardous but attractive substances and activities have a long history, though prior to the late 19th century often motivated more by revenue needs than by public health and welfare.A narrative review considering lessons from alcohol for monopolization of all or part of legal markets in cannabis as a strategy for public health and welfare.A monopoly can constrain levels of use and harm from use through such mechanisms as price, limits on times and places of availability, and effective implementation of restrictions on who can purchase, and less directly by replacing private interests who would promote sales and press for greater availability, and as a potential test-bed for new policies. But such monopolies can also push in the opposite direction, particularly if revenue becomes the prime consideration. Drawing on the alcohol experience in recent decades, the paper discusses issues relevant to cannabis legalization in monopolization of different market levels and segments - production, wholesale, import, retail for off-site and for on-site use - and choices about the structuring and governance of monopolies and their organizational location in government, from the perspective of maximizing public health and welfare interests.While the historical record is mixed for government monopolies of attractive but hazardous commodities, experience with alcohol in recent decades shows that for public health and welfare public monopolization is generally a preferable option.

Cannabis use has been rising despite recognition of the negative consequences associated with heavy use. The severity of these consequences has been shown to differ across racial/ethnic groups, even when controlling for consumption levels. The present study conducted an item response theory (IRT) analysis of the Cannabis Use Disorders Identification Test (CUDIT) to better understand the patterns of problematic cannabis use and their relation with other substance use across ethnic groups in the Healthy Life in an Urban Setting (HELIUS) study. CUDIT responses from 1,960 cannabis-using African Surinamese, South-Asian Surinamese, Dutch, Moroccan, and Turkish ethnic origin participants were used to test for differential item functioning (DIF) within an IRT framework. After restricting the sample to men because of low frequency of use among women, several instances of uniform DIF were identified. Multiple-group IRT analysis yielded a harmonized cannabis use phenotype that was used to estimate ethnic group differences in problematic cannabis use and its relation to alcohol and tobacco co-use. These analyses suggested that cannabis users from certain ethnic minority groups experienced higher rates of problematic use than the majority group despite lower rates of cannabis use. Further, cannabis and tobacco use were positively related across groups, whereas only ethnic minority groups showed a positive relation between cannabis and alcohol use. These results demonstrate the importance of accounting for DIF when examining group differences in problematic cannabis use, and support prior evidence suggesting that certain ethnic minority groups may be more likely to experience problematic cannabis use and alcohol co-use relative to the majority group. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Cocaine and ethanol (EtOH) co-consumption is a risk factor for physiologically and clinically negative outcomes. We describe the occurrence of cocaine consumption alone or co-consumption with EtOH and others psychotropics.The descriptive research used data on medical records of patients positive to cocaine test who attended an emergency room between 2016 and 2017. We determined the frequency of cocaine consumption alone and co-consumption with EtOH, cannabis or benzodiazepines (BZDs).Over one year period, 88 patients (13.3%) were positive to cocaine test, mainly attended on weekends, in holiday months, young adults or men. Among those positive for cocaine, 72% were also positive for EtOH, cannabis or BZD. Cocaine co-consumption with one or two out of three substance was 55.2% (CI95%; 44.7-65.8%) and 16.4% (CI95%;8.58-24.3%), respectively. Co-consumption was more frecuently wih EtOH, followed by cannabis or BZD.Co-consumption of cocaine with EtOH is very common and could be associated with acute or chronic consumption of cannabis or acute exposure to BZDs. It is important that emergency physicians use a systematic approach to diagnose and treat more than one psychotropic substance in cocaine positive patients.

Cannabis (marijuana) is one of the most consumed psychoactive substances in the world. The term marijuana is of Mexican origin. The primary cannabinoids that have been studied to date include cannabidiol and delta-9-tetrahydrocannabinol, which is responsible for most cannabis physical and psychotropic effects. Recently, the endocannabinoid system was discovered, which is made up of receptors, ligands and enzymes that are widely expressed in the brain and its periphery, where they act to maintain balance in several homeostatic processes. Exogenous cannabinoids or naturally-occurring phytocannabinoids interact with the endocannabinoid system. Marijuana must be processed in a laboratory to extract tetrahydrocannabinol and leave cannabidiol, which is the product that can be marketed. Some studies suggest cannabidiol has great potential for therapeutic use as an agent with antiepileptic, analgesic, anxiolytic, antipsychotic, anti-inflammatory and neuroprotective properties; however, the findings on cannabinoids efficacy and cannabis-based medications tolerability-safety for some conditions are inconsistent. More scientific evidence is required in order to generate recommendations on the use of medicinal cannabis.

Cannabis use is rising, yet there is poor understanding of biological processes that might link chronic cannabis use to brain structural abnormalities. To lend insight into this topic, we examined white matter microstructural integrity and gray matter cortical thickness/density differences between 89 individuals with cannabis dependence (CD) and 89 matched controls (64 males, 25 females in each group) from the Human Connectome Project. We tested whether cortical patterns for expression of genes relevant for cannabinoid signaling (from Allen Human Brain Atlas postmortem tissue) were associated with spatial patterns of cortical thickness/density differences in CD. CD had lower fractional anisotropy than controls in white matter bundles innervating posterior cingulate and parietal cortex, basal ganglia, and temporal cortex. The CD group also had significantly less gray matter thickness and density in precuneus, relative to controls. Sibling-pair analysis found support for causal and graded liability effects of cannabis on precuneus structure. Spatial patterns of gray matter differences in CD were significantly associated with regional differences in monoacylglycerol lipase (MAGL) expression in postmortem brain tissue, such that regions with higher MAGL expression (but not fatty-acid amide hydrolase or FAAH) were more vulnerable to cortical thinning. In sum, chronic cannabis use is associated with structural differences in white and gray matter, which was most prominent in precuneus and associated white matter tracts. Regions with high MAGL expression, and therefore with potentially physiologically restricted endogenous cannabinoid signaling, may be more vulnerable to the effects of chronic cannabis use on cortical thickness.

The French Addictovigilance Network aims to monitor all psychoactive substances with abuse potential including prescription drugs and other legal and illegal substances such as new psychoactive substances (NPS) and its consequences in humans. Created in 1990 through a network of regional addictovigilance centres covering the entire country, these pharmacologists with expertise in addictovigilance have developed interface with different partners (physicians, toxicologists, network of community pharmacies, addictology care centers…) and implemented several original tools of pharmacosurveillance (such as DRAMES [death related to the abuse of medicines] in strong collaboration with toxicologists or such OPPIDUM [observation of illegal products and misuse of psychotropic medications]), complementary to the spontaneous reporting. A such multidimensional approach including proactive surveillance by these tools and also among several heterogenous data sources (such as data from hospitals or claims database) is able to detect early addictovigilance signals and warnings as illustrated with three following examples: cannabis use and acute serious cardiovascular disorders, new synthetic opioids (ocfentanil, carfentanil) and severe opiate overdose or deaths, the diverted use of psychoactive drugs (codeine analgesics or sedative H1 antihistamines called purple drank) by adolescents and young adults. The choice of a broad strategy and the multifaceted system implemented by the French Addictovigilance Network using elements of pharmacology (fundamental, clinical, pharmacoepidemiology) expertise is an innovative method to detect early addictovigilance signals, and to describe its characteristics in order to increase awareness of psychoactive substances by patients, users and health professionals.

For persons living with chronic conditions, health-related quality of life (HRQoL) symptoms, such as pain, anxiety, depression, and insomnia, often interact and mutually reinforce one another. There is evidence that medical cannabis (MC) may be efficacious in ameliorating such symptoms and improving HRQoL. As many of these HRQoL symptoms may mutually reinforce one another, we conducted an exploratory study to investigate how MC users perceive the efficacy of MC in addressing co-occurring HRQoL symptoms. We conducted a cross-sectional online survey of persons with a state medical marijuana card in Illinois (N = 367) recruited from licensed MC dispensaries across the state. We conducted tests of ANOVA to measure how perceived MC efficacy for each HRQoL symptom varied by total number of treated symptoms reported by participants. Pain was the most frequently reported HRQoL treated by MC, followed by anxiety, insomnia, and depression. A large majority of our sample (75%) reported treating two or more HRQoL symptoms. In general, perceived efficacy of MC in relieving each HRQoL symptom category increased with the number of co-occurring symptoms also treated with MC. Perceived efficacy of MC in relieving pain, anxiety, and depression varied significantly by number of total symptoms experienced. This exploratory study contributes to our understanding of how persons living with chronic conditions perceive the efficacy of MC in treating co-occurring HRQoL symptoms. Our results suggest that co-occurring pain, anxiety, and depression may be particularly amenable to treatment with MC.

To evaluate interest in and patterns of use of non-prescription cannabis products for symptom management amongst gynecologic cancer patients living in states with legal access to medical and recreational marijuana.Cross-sectional study using a novel 35-question survey distributed to women diagnosed with gynecologic cancer within two academic centers in California and Colorado. The survey queries demographic and disease traits, and both objective and subjective issues surrounding use of cannabis products for symptom management. Surveys were distributed to patients actively receiving treatment or under surveillance.Enrollment began July 16, 2018 and was completed December 1, 2018. Survey return rate was 52.7%. A total of 225 participants met inclusion criteria.Sixty-two percent reported that they have used or would be interested in using cannabis products for symptom management; 60 (26.7%) are using non-prescription cannabis for treatment of cancer related symptoms, and 80 (35.6%) are interested in using cannabis derivatives under direction of their oncologist. Reasons cited for use of cannabis included: pain control (n = 41, 68.3), insomnia (n = 33, 55.0%), anxiety (n = 29, 48.3%), nausea (n = 26, 43.3%), and appetite stimulation (n = 21, 35.0%). Of the women using cannabis products, almost half report decreased prescription narcotic use after initiation of cannabis products (n = 27, 45.0%).Women with gynecologic cancer report a strong interest in the use of non-prescription cannabis products for management of cancer-related symptoms. Practitioners in the field of gynecologic oncology should be aware of the frequency of use of non-prescription cannabis amongst their patients as well as the growing desire for guidance about the use of cannabis derivatives. A substantial number of patients report decreased reliance on opioids when using cannabis derivatives for pain control.

The purpose of this paper was to study the extraction conditions of hemp proteins from undelipidated press-cakes. The effects of different hydration conditions on protein recovery yield and polypeptide profile were evaluated: pH (2 to 12), ionic strength (0 to 500 mM NaCl) and press-cake/liquid weight ratio (2% to 22%). pH was the most impacting factor. At acidic pH (2 to 7) the extraction yields were low and quite constant (<7%), corresponding mainly to hemp albumins solubilization. The extraction of globulins started to increase significantly from pH 8, with protein extraction yield varying from 8.3% at pH 8 to 67.1% at pH 12 for a 10% press-cake/liquid weight ratio. The addition of NaCl in press-cake suspensions did not increase the total nitrogen content in aqueous extracts at alkaline pH while the lowest press-cake/liquid weight ratios (5% to 10%) were revealed optimal regarding protein recovery rate. The intense coloration observed on the aqueous extracts above pH 8 was assigned to solubilization and oxidation of phenolic compounds whose concentration increased about sevenfolds from pH 2 to 12. At the highest applied pH (11 to 12), the formation of covalent complexes between phenolic compounds and some hemp polypeptides was hypothesized. Aqueous extraction at strong alkaline pH (>9) without salt addition and respecting a 10% press-cake/liquid weight ratio should be retained to optimize protein extraction yield. However, further purification steps are required to evaluate the nutritional, organoleptic, and techno-functional properties of hemp proteins extracted in such conditions. PRACTICAL APPLICATION: The traditional extraction process of hemp proteins by alkaline solubilization and isoelectric precipitation, mostly from delipidated hemp press-cake, leads to limited quantity and poor solubility of extracted proteins, and data related to extraction conditions are insufficiently available to optimize this process. This article aims to find optimal hydration conditions (pH, ionic strength, press-cake to liquid ratio) for protein extraction from undelipidated hemp press-cake, allowing high protein recovery and preserving protein quality. The results obtained represent very useful data for developing an economically viable and sustainable extraction process of proteins from raw hemp press-cake.

Refugees are at higher risk of some psychiatric disorders, including post-traumatic stress disorder (PTSD) and psychosis, compared with other non-refugee migrants and the majority population. However, it is unclear whether this also applies to substance use disorders, which we investigated in a national register cohort study in Sweden. We also investigated whether risk varied by region of origin, age at migration, time in Sweden, and diagnosis of PTSD.Using linked Swedish register data, we followed a cohort born between 1984 and 1997 from their 14th birthday or arrival in Sweden, if later, until an International Classification of Diseases, 10th revision (ICD-10), diagnosis of substance use disorder (codes F10.X-19.X), emigration, death, or end of follow-up (31 December 2016). Refugee and non-refugee migrants were restricted to those from regions with at least 1,000 refugees in the Swedish registers. We used Cox proportional hazards regression to estimate unadjusted and adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) in refugee and non-refugee migrants, compared with Swedish-born individuals, for all substance use disorders (F10.X-19.X), alcohol use disorders (F10.X), cannabis use disorders (F12.X), and polydrug use disorders (F19.X). In adjusted analyses, we controlled for age, sex, birth year, family income, family employment status, population density, and PTSD diagnosis. Our sample of 1,241,901 participants included 17,783 (1.4%) refugee and 104,250 (8.4%) non-refugee migrants. Refugees' regions of origin were represented in proportions ranging from 6.0% (Eastern Europe and Russia) to 41.4% (Middle East and North Africa); proportions of non-refugee migrants' regions of origin ranged from 11.8% (sub-Saharan Africa) to 33.7% (Middle East and North Africa). These groups were more economically disadvantaged at cohort entry (p < 0.001) than the Swedish-born population. Refugee (aHR: 0.52; 95% CI 0.46-0.60) and non-refugee (aHR: 0.46; 95% CI 0.43-0.49) migrants had similarly lower rates of all substance use disorders compared with Swedish-born individuals (crude incidence: 290.2 cases per 100,000 person-years; 95% CI 287.3-293.1). Rates of substance use disorders in migrants converged to the Swedish-born rate over time, indicated by both earlier age at migration and longer time in Sweden. We observed similar patterns for alcohol and polydrug use disorders, separately, although differences in cannabis use were less marked; findings did not differ substantially by migrants' region of origin. Finally, while a PTSD diagnosis was over 5 times more common in refugees than the Swedish-born population, it was more strongly associated with increased rates of substance use disorders in the Swedish-born population (aHR: 7.36; 95% CI 6.79-7.96) than non-refugee migrants (HR: 4.88; 95% CI 3.71-6.41; likelihood ratio test [LRT]: p = 0.01). The main limitations of our study were possible non-differential or differential under-ascertainment (by migrant status) of those only seen via primary care and that our findings may not generalize to undocumented migrants, who were not part of this study.Our findings suggest that lower rates of substance use disorders in migrants and refugees may reflect prevalent behaviors with respect to substance use in migrants' countries of origin, although this effect appeared to diminish over time in Sweden, with rates converging towards the substantial burden of substance use morbidity we observed in the Swedish-born population.

Prescription opioid misuse has become a leading cause of unintentional injury and death among adolescents and young adults in the United States. However, there is limited information on how adolescents and young adults obtain prescription opioids. There are also inadequate recent data on the prevalence of additional drug abuse among those misusing prescription opioids. In this study, we evaluated past-year prevalence of prescription opioid use and misuse, sources of prescription opioids, and additional substance use among adolescents and young adults.This was a retrospective analysis of the National Survey on Drug Use and Health (NSDUH) for the years 2015 and 2016. Prevalence of opioid use, misuse, use disorder, and additional substance use were calculated with 95% confidence intervals (CIs), stratified by age group and other demographic variables. Sources of prescription opioids were determined for respondents reporting opioid misuse. We calculated past-year prevalence of opioid use and misuse with or without use disorder, sources of prescription opioids, and prevalence of additional substance use. We included 27,857 adolescents (12-17 years of age) and 28,213 young adults (18-25 years of age) in our analyses, corresponding to 119.3 million individuals in the extrapolated national population. There were 15,143 respondents (27.5% [95% CI 27.0-28.0], corresponding to 32.8 million individuals) who used prescription opioids in the previous year, including 21.0% (95% CI 20.4-21.6) of adolescents and 32.2% (95% CI 31.4-33.0) of young adults. Significantly more females than males reported using any prescription opioid (30.3% versus 24.8%, P < 0.001), and non-Hispanic whites and blacks were more likely to have had any opioid use compared to Hispanics (28.9%, 28.1%, and 25.8%, respectively; P < 0.001). Opioid misuse was reported by 1,050 adolescents (3.8%; 95% CI 3.5-4.0) and 2,207 young adults (7.8%; 95% CI 7.3-8.2; P < 0.001). Male respondents using opioids were more likely to have opioid misuse without use disorder compared with females (23.2% versus 15.8%, respectively; P < 0.001), with similar prevalence by race/ethnicity. Among those misusing opioids, 55.7% obtained them from friends or relatives, 25.4% from the healthcare system, and 18.9% through other means. Obtaining opioids free from friends or relatives was the most common source for both adolescents (33.5%) and young adults (41.4%). Those with opioid misuse reported high prevalence of prior cocaine (35.5%), hallucinogen (49.4%), heroin (8.7%), and inhalant (30.4%) use. In addition, at least half had used tobacco (55.5%), alcohol (66.9%), or cannabis (49.9%) in the past month. Potential limitations of the study are that we cannot exclude selection bias in the study design or socially desirable reporting among participants, and that longitudinal data are not available for long-term follow-up of individuals.Results from this study suggest that the prevalence of prescription opioid use among adolescents and young adults in the US is high despite known risks for future opioid and other drug use disorders. Reported prescription opioid misuse is common among adolescents and young adults and often associated with additional substance abuse, underscoring the importance of drug and alcohol screening programs in this population. Prevention and treatment efforts should take into account that greater than half of youths misusing prescription opioids obtain these medications through friends and relatives.

The change in legal status of cannabis (the botanical species Cannabis sativa, commonly known as marijuana) in the United States has had significant impact on pediatric drug exposures. In states with decriminalization of recreational and medicinal use of cannabis, emergency department visits and poison control center calls for unintentional pediatric cannabis intoxication are on the rise in the last few decades. Exploratory or unintentional ingestions of cannabis-containing products (as opposed to those derived from synthetic cannabinoids, which may mimic the structure and/or function of cannabis, but are not the focus of this article) can lead to significant pediatric toxicity, including encephalopathy, coma, and respiratory depression. With the increasing magnitude of the public health implications of widespread cannabis use, clinicians who care for pediatric patients routinely must be adept in the recognition, evaluation, management, and counseling of unintentional cannabis exposure.

Most clinical and epidemiologic estimates of prenatal cannabis use are based on self-report, and the validity of self-reported cannabis use has not been examined in a large, representative population of pregnant women. We determined the validity of self-reported prenatal cannabis use and predictors of nondisclosure using data from Kaiser Permanente Northern California's (KPNC) healthcare system with universal prenatal cannabis screening during prenatal care.Validation study using data from 281,025 pregnancies in KPNC among females aged ≥11 years who completed a self-administered questionnaire on prenatal cannabis use and a cannabis urine toxicology test from 2009 to 2017. We calculated sensitivity, specificity, positive predictive value, and negative predictive value of self-reported prenatal cannabis use using urine toxicology testing as the criterion standard, and sensitivity of urine toxicology testing using self-reported use as the criterion standard. We compared sociodemographics of those who disclosed versus did not disclose prenatal cannabis use.Urine toxicology testing identified more instances of prenatal cannabis use than self-report (4.9% vs 2.5%). Sensitivity of self-reported use was low (33.9%). Sensitivity of the toxicology test was higher (65.8%), with greater detection of self-reported daily (83.9%) and weekly (77.4%) than monthly or less use (54.1%). Older women, those of Hispanic race/ethnicity, and those with lower median neighborhood incomes were most likely to be misclassified as not using cannabis by self-reported screening.Given that many women choose not to disclose prenatal cannabis use, clinicians should educate all prenatal patients about the potential risks and advise them to quit cannabis use during pregnancy.

Background: Pain is the most frequent indication for which medical cannabis treatment is sought.Objectives: The clinical potential of cannabis and cannabis-derived products (CDPs) relies on their efficacy to treat an indication and potential adverse effects that impact outcomes, including abuse liability and neurocognitive effects. To ascertain the extent to which these effects impact therapeutic utility, studies investigating cannabis and CDPs for pain were reviewed for analgesic efficacy and assessments of abuse liability and neurocognitive effects.Methods: A comprehensive review of placebo-controlled studies investigating cannabis and CDP analgesia was performed. Methods and findings related to adverse effects, abuse liability, and neurocognitive effects were extracted.Results: Thirty-eight studies were reviewed; 29 assessed cannabis and CDPs for chronic pain, 1 for acute pain, and 8 used experimental pain tests. Most studies ascertained adverse effects through self-report (N = 27). Fewer studies specifically probed abuse liability (N = 7) and cognitive and psychomotor effects (N = 12). Many studies related to chronic and experimental pain (N = 18 and N = 5, respectively) found cannabis and CDPs to reduce pain. Overall, adverse effects were mild to moderate, and dose-related. Studies investigating the impact of cannabis and CDPs on abuse liability and neurocognitive endpoints were mostly limited to inhaled administration and confirmed dose-related effects.Conclusion: Few studies investigating cannabis and CDP analgesia assess abuse liability and cognitive endpoints, adverse effects that impact the long-term clinical utility of these drugs. Future studies should include these measures to optimize research and clinical care related to cannabis-based therapeutics.

Objective: The purpose of this study was to investigate the effect of perceived social support on the quality of life of male patients with alcohol, opiate and synthetic cannabinoid use disorders by considering sociodemographic factors and mood, and to compare these three groups in terms of social support and quality of life.Method: One hundred and thirtyone (131) patients who were hospitalized at Addiction Clinic of Istanbul Erenkoy Psychiatric and Neurological Diseases Training and Research Hospital in Turkey and diagnosed as alcohol, opiate and synthetic cannabinoid use disorder were included in the study. Sociodemographic Data Form, Turkish version of the World Health Organization Quality of Life Questionnaire Scale (WHOQOL-BREF-TR), Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI), Multidimensional Scale of Perceived Social Support (MSPSS), API (Addiction Profile Index) were applied to the participants.Results: A total of 131 male patients were 32 synthetic cannabinoids, 51 opiates and 48 alcohol use disorders diagnosed. The mean age of alcohol users was higher than the other groups. Separation/divorce rate was higher in alcohol users and single rate in opiate users. Alcohol use was higher in living alone and opiate users lived with first degree relatives. The crime history was higher in the cannabis group. Prison experience, probation and self-injury were higher among opiate users. Family history of substance use was higher in opiate users. Crime was found to be less in alcohol users. In the comparison of alcohol and substance (opiate, cannabis) groups, the rate of self-injury (93.8%) was found to be significantly higher in the substance user' group. There was no statistically significant difference between the groups in terms of depression and anxiety scores. When the alcohol and substance (opiate, cannabis) comparisons were made between the groups, the mean depression (21.02 ± 11.6) and anxiety (20.09 ± 17.49) of the alcohol group was significantly higher. The "effect on life" (31.8 ± 6.13) and "motivation" subscales (10.38 ± 2.39) of API was found to be significantly higher in patients with substance use. In the opioid group, physical, environmental and psychological subscales of the WHOQOL-BREF-TR did not show significant correlation with MSPSS, and the family, friend' subscales and total perceived social support were significantly correlated with the social subscale of WHOQOL-BREF-TR. In the alcohol group, the environmental and social subscales of WHOQOL-BREF-TR showed a significant correlation with perceived social support from the family and private person and total perceived support.Conclusion: Addiction is a recurrent and chronic disease and inevitably reduces quality of life. Social support has an important role on the quality of life. Improving the quality of life seems to be one of the main goals during the addiction treatment. For this purpose, it is very important to provide psychosocial support with pharmacological treatment by evaluating the medical, mental and social needs of the dependent patient as a whole.

Cannabis sativa produces a complex mixture of many bioactive molecules including terpenophenolic compounds known as phytocannabinoids. Phytocannabinoids come in neutral forms (e.g., Δ9-tetrahydrocannabinol, THC; cannabidiol, CBD; etc.) or as acid precursors, which are dominant in the plant (e.g., Δ9-tetrahydrocannabinolic acid, THCA; cannabidiolic acid, CBDA; etc.). There is increasing interest in unlocking the therapeutic applications of the phytocannabinoid acids; however, the present understanding of the basic pharmacology of phytocannabinoid acids is limited. Herein the brain and plasma pharmacokinetic profiles of CBDA, THCA, cannabichromenic acid (CBCA), cannabidivarinic acid (CBDVA), cannabigerolic acid (CBGA), and cannabigerovarinic acid (CBGVA) were examined following intraperitoneal administration in mice. Next it was examined whether CBDA was anticonvulsant in a mouse model of Dravet syndrome (Scn1aRX/+ mice). All the phytocannabinoid acids investigated were rapidly absorbed with plasma tmax values of between 15 and 45 min and had relatively short half-lives (<4 h). The brain-plasma ratios for the acids were very low at ≤0.04. However, when CBDA was administered in an alternate Tween 80-based vehicle, it exhibited a brain-plasma ratio of 1.9. The anticonvulsant potential of CBDA was examined using this vehicle, and it was found that CBDA significantly increased the temperature threshold at which the Scn1aRX/+ mice had a generalized tonic-clonic seizure.

The endocannabinoid (eCB) system, i.e. the receptors that respond to the psychoactive component of cannabis, their endogenous ligands and the ligand metabolic enzymes, is part of a larger family of lipid signals termed the endocannabinoidome (eCBome). We summarize recent discoveries of the roles that the eCBome plays within peripheral tissues in diabetes, and how it is being targeted, in an effort to develop novel therapeutics for the treatment of this increasingly prevalent disease.As with the eCB system, many eCBome members regulate several physiological processes, including energy intake and storage, glucose and lipid metabolism and pancreatic health, which contribute to the development of type 2 diabetes (T2D). Preclinical studies increasingly support the notion that targeting the eCBome may beneficially affect T2D. The eCBome is implicated in T2D at several levels and in a variety of tissues, making this complex lipid signaling system a potential source of many potential therapeutics for the treatments for T2D.

Psychoactive substance use is lower among married compared to divorced or unmarried men; yet, the nature of this effect remains unclear because becoming and staying married is potentially confounded with substance-related background familial and individual factors, like parental divorce and personality. The authors investigated the associations between marital status and substance use; how substance use changed across the transition to marriage; and whether marriage effects were likely to be causal.The sample included 1790 adults from male-male twin pairs from a population-based registry. Measures of marital status and alcohol, tobacco, and cannabis use came from Life History Calendars. Data were analyzed using regression, co-twin comparison, and within-person models. The latter models are tools for quasi-causal inference that control for familial and individual-level confounders.Married men used less alcohol, tobacco, and cannabis than men who were divorced/separated or single. In analyses of substance use across the transition to marriage, men reduced their alcohol and cannabis use both before and after marriage, but their tobacco use only after marriage. These effects were largely robust in co-twin and within-person analyses.Marriage was associated with substantial reductions in substance use compared to being divorced/separated or single, and these reductions began prior to marriage. The co-twin comparison and within-person models ruled out the alternative explanation that marriage effects were due to confounding background familial and individual factors. These results provide strong evidence that the social role expectations associated with marriage reduce psychoactive substance use.

Post-traumatic stress disorder sharply increases the risk of depression and suicide. Individuals living with post-traumatic stress disorder frequently use cannabis to treat associated symptoms. We sought to investigate whether cannabis use modifies the association between post-traumatic stress disorder and experiencing a major depressive episode or suicidal ideation.We used data from the 2012 Canadian Community Health Survey-Mental Health, a nationally representative cross-sectional survey of non-institutionalized Canadians aged ⩾15 years. The relationship between post-traumatic stress disorder and each outcome was modelled using logistic regression with an interaction term for cannabis and post-traumatic stress disorder, controlling for demographic characteristics, mental health, and substance use comorbidities. The ratio of odds ratios and relative excess risk due to interaction was calculated to measure interaction on the multiplicative and additive scales, respectively.Among 24,089 eligible respondents, 420 (1.7%) reported a current clinical diagnosis of post-traumatic stress disorder. In total, 106 (28.2%) people with post-traumatic stress disorder reported past-year cannabis use, compared to 11.2% of those without post-traumatic stress disorder (p < 0.001). In multivariable analyses, post-traumatic stress disorder was significantly associated with recent major depressive episode (adjusted odds ratio = 7.18, 95% confidence interval: 4.32-11.91) and suicidal ideation (adjusted odds ratio = 4.76, 95% confidence interval: 2.39-9.47) among cannabis non-users. post-traumatic stress disorder was not associated with either outcome among cannabis-using respondents (both p > 0.05).This study provides preliminary epidemiological evidence that cannabis use may contribute to reducing the association between post-traumatic stress disorder and severe depressive and suicidal states. There is an emerging need for high-quality experimental investigation of the efficacy of cannabis/cannabinoids for the treatment of post-traumatic stress disorder.

Older adults may benefit from cannabis treatment for various symptoms such as chronic pain, sleep difficulties, and others, that are not adequately controlled with evidence-based therapies. However, currently, there is a dearth of evidence about the efficacy and safety of cannabis treatment for these patients. This article aims to present a pragmatic treatment protocol for medical cannabis in older adults. We followed consecutive patients above 65 years of age prospectively who were treated with medical cannabis from April 2017 to October 2018. The outcomes included treatment adherence, global assessment of efficacy and adverse events after six months of treatment. During the study period, 184 patients began cannabis treatment, 63.6% were female, and the mean age was 81.2 ± 7.5 years (median age-82). After six months of treatment, 58.1% were still using cannabis. Of these patients, 33.6% reported adverse events, the most common of which were dizziness (12.1%) and sleepiness and fatigue (11.2%). Of the respondents, 84.8% reported some degree of improvement in their general condition. Special caution is warranted in older adults due to polypharmacy, pharmacokinetic changes, nervous system impairment, and increased cardiovascular risk. Medical cannabis should still be considered carefully and individually for each patient after a risk-benefit analysis and followed by frequent monitoring for efficacy and adverse events.

Substance use patterns and sociodemographic variables of Berlin's party scene were investigated to derive preventive measures and harm reduction services, which meet the needs of the consumers.A questionnaire was used online and in the field among Berlin partygoers (N = 877) and structured interviews (N = 20) were conducted with professionals working in this area, including social workers, emergency medical service, police and club owners and users.A risky consumption pattern was found in 67 % of participants, who also stated need for counseling and a wish for reduction of their substance use. Of all preventive measures, drug checking was requested most often. Substances with the highest prevalence were alcohol, cannabis, amphetamine, MDMA, cocaine and ketamine, whereas methamphetamine and new psychoactive substances were barely stated.There is an urgent need to expand current preventive measures. There is a willingness of the scene to use according services, especially by those who need it the most.

Cannabis use is frequent among individuals with cocaine use disorder. Despite recent non-controlled studies advocating a therapeutic role of smoked cannabis, there is a paucity of evidence-based data on potential therapeutic and cognitive side-effects of this association.We examined 63 cocaine-addicted subjects who used cannabis more than 50 times in lifetime (COC + CAN), 24 cocaine-addicted patients who use cannabis less than 50 times (COC), and 36 controls (CON). Participants were evaluated with an extensive battery of neurocognitive tests after two weeks of supervised detoxification in an inpatient treatment program. Patients were followed up in one, three, and six months after discharge.Both groups of patients performed worse than CON on working memory, processing speed, inhibitory control, mental flexibility, and decision making. COC + CAN performed worse than COC on speed processing, inhibitory control and sustained attention, while COC performed worse than COC + CAN on mental flexibility. Concomitant cannabis use did not decrease relapses to cocaine use after one, three and six months. Among COC + CAN, earlier cocaine and cannabis use, and impaired executive functioning were predictive of relapse on cocaine after six months.Our results did not support the recommendation of smoked cannabis as a safe therapeutic approach for cocaine-addicted patients due to significant negative cognitive side-effects and absence of efficacy. Further studies investigating frontal brain morphology, neuromaturation, and prescription of the non-psychoactive constituent of cannabis sativa cannabidiol among cocaine-addicted patients who use cannabis are warranted.

The purpose of this study is to evaluate five self-report, non-proprietary questionnaires in the identification of substance use disorders [including alcohol, cannabis, opioids, and stimulants] among pregnant women.A total of 1220 pregnant women completed the NIDA Quick Screen, CRAFFT, Substance Use Risk Profile-Pregnancy (SURP-P), Wayne Indirect Drug Use Questionnaire (WIDUS), and the 5 Ps, as well as the MINI diagnostic interview for substance use disorders, which served as the reference standard. Measures of merit calculated for each screener included sensitivity, specificity, accuracy, and area under the receiver operating curve (AUROC).The participants were socioeconomically diverse, with a mean age of 29 years. Over 15% met diagnostic criteria for a substance use disorder. AUROCS for identifying any substance use disorder (including alcohol) ranged from a high of 0.75 for the CRAFFT (95% CI = 0.72-79) and 0.74 for the SURP-P (95% CI = 0.71-.78) to a low of 0.62 for the NIDA Quick Screen (95% CI = 0.59-.65). Overall accuracy of most tested measures was higher for identification of alcohol use disorders than for other substance use disorders (e.g., AUROCs for the CRAFFT and SURP-P for identifying alcohol use disorders were 0.78 and 0.77, respectively).The CRAFFT and SURP-P showed modest ability to identify substance use disorders among pregnant women. Future research is needed to develop an ideal questionnaire set in the complicated societal context which includes increasing rates of use and potential sanction.

Genipin, a natural electrophilic cross-linker, was applied (5, 10, 20, and 30 mM) to modify hempseed protein isolate (HPI). Genipin treatments resulted in general losses of total sulfhydryls (up to 2.9 nmol/mg) and free amines (up to 77.3 nmol/mg). Surface hydrophobicity decreased by nearly 90% with 30 mM genipin, corresponding to similar tryptophan fluorescence quenching. The genipin treatment converted HPI into highly cross-linked polymers. Hydrogels formed with such polymers when also incorporated with hemp oil emulsions exhibited substantially enhanced gelling ability: up to 3.3- and 2.6-fold increases, respectively, in gel strength and gel elasticity over genipin-untreated protein. The genipin-modified composite gels also exhibited superior water-holding capacity. Microstructural analysis revealed a compact gel network filled with protein-coated oil globules that interacted intimately with the protein matrix when treated with genipin. Such gels remained readily digestible. Hence, genipin-treated hemp protein hydrogels show promise as functional food components.

This study aimed to evaluate the attitudes of health professionals toward the use of medicinal cannabis as part of the management of patients with cancer. A prospective, cross-sectional study was conducted using an anonymous survey, emailed out to health professionals at a public metropolitan hospital in Australia. One hundred and thirty-five responses were received. 62% of survey respondents reported that patients inquire about medicinal cannabis. More than half of the health professionals stated being insufficiently informed about access to medicinal cannabis (74%), about its evidence base (59%), and about potential drug interactions (65%). Thirty-four percent would recommend medicinal cannabis to their patients with cancer, 20% would not, and 46% were unsure. Comments indicated concerns about lack of clinician knowledge, drug efficacy, side effects and drug interactions. The results show that health professionals feel insufficiently informed about access to, and use of, medicinal cannabis as part of cancer management. More information and education are required for health professionals to consider medicinal cannabis as part of care provided to their patients with cancer.

Cannabis products in which cannabidiol (CBD) is the primary chemical constituent (CBD-dominant) are increasingly popular and widely available. The impact of CBD exposure on urine drug testing has not been well studied. This study characterized the urinary pharmacokinetic profile of 100-mg oral and vaporized CBD, vaporized CBD-dominant cannabis (100-mg CBD; 3.7-mg ∆9-THC) and placebo in healthy adults (n = 6) using a within-subjects crossover design. Urine specimens were collected before and for 5 days after drug administration. Immunoassay (IA) screening (cutoffs of 20, 50 and 100 ng/mL) and LC-MS-MS confirmatory tests (cutoff of 15 ng/mL) for 11-nor-9-carboxy-∆9-tetrahydrocannabinol (∆9-THCCOOH) were performed; urine was also analyzed for CBD and other cannabinoids. Urinary concentrations of CBD were higher after oral (mean Cmax: 776 ng/mL) versus vaporized CBD (mean Cmax: 261 ng/mL). CBD concentrations peaked 5 h after oral CBD ingestion and within 1 h after inhalation of vaporized CBD. After pure CBD administration, only 1 out of 218 urine specimens screened positive for ∆9-THCCOOH (20-ng/mL IA cutoff) and no specimens exceeded the 15-ng/mL confirmatory cutoff. After inhalation of CBD-dominant cannabis vapor, nine samples screened positive at the 20-ng/mL IA cutoff, and two of those samples screened positive at the 50-ng/mL IA cutoff. Four samples that screened positive (two at 20 ng/mL and two at 50 ng/mL) confirmed positive with concentrations of ∆9-THCCOOH exceeding 15 ng/mL. These data indicate that acute dosing of pure CBD will not result in a positive urine drug test using current federal workplace drug testing guidelines (50-ng/mL IA cutoff with 15-ng/mL confirmatory cutoff). However, CBD products that also contain ∆9-THC may produce positive urine results for ∆9-THCCOOH. Accurate labeling and regulation of ∆9-THC content in CBD/hemp products are needed to prevent unexpected positive drug tests and unintended drug effects.

This study examines self-reported 30-day antiretroviral therapy (ART) adherence among 101 people living with HIV and substance use disorders (SUD) in New York City in terms of Diagnostic and Statistical Manual - 5th Edition (DSM-5) SUD symptom clusters: impaired control, social impairment, risky use and pharmacological criteria. Overall, 60.4% met DSM-5 criteria for stimulant, 55.5% for alcohol, 34.7% for cannabis and 25.7% for opioid SUD. Of the 76 participants with a current ART prescription, 75.3% reported at least 90% 30-day adherence. Participants with vs. without alcohol SUD were significantly less likely to report ART adherence (64.3% vs. 88.2%, p = .017). Endorsement of social impairment significantly differed among adherent vs. non-adherent participants with alcohol SUDs (74.1% vs. 100%, p = .038) and with opioid SUDs (94.1% vs. 50.0%, p = .040). Understanding specific SUD symptom clusters may assist providers and patients in developing strategies to improve ART adherence.

Plant pathogens infecting marijuana (Cannabis sativa L.) plants reduce growth of the crop by affecting the roots, crown, and foliage. In addition, fungi (molds) that colonize the inflorescences (buds) during development or after harvest, and which colonize internal tissues as endophytes, can reduce product quality. The pathogens and molds that affect C. sativa grown hydroponically indoors (in environmentally controlled growth rooms and greenhouses) and field-grown plants were studied over multiple years of sampling. A PCR-based assay using primers for the internal transcribed spacer region (ITS) of ribosomal DNA confirmed identity of the cultures. Root-infecting pathogens included Fusarium oxysporum, Fusarium solani, Fusarium brachygibbosum, Pythium dissotocum, Pythium myriotylum, and Pythium aphanidermatum, which caused root browning, discoloration of the crown and pith tissues, stunting and yellowing of plants, and in some instances, plant death. On the foliage, powdery mildew, caused by Golovinomyces cichoracearum, was the major pathogen observed. On inflorescences, Penicillium bud rot (caused by Penicillium olsonii and Penicillium copticola), Botrytis bud rot (Botrytis cinerea), and Fusarium bud rot (F. solani, F. oxysporum) were present to varying extents. Endophytic fungi present in crown, stem, and petiole tissues included soil-colonizing and cellulolytic fungi, such as species of Chaetomium, Trametes, Trichoderma, Penicillium, and Fusarium. Analysis of air samples in indoor growing environments revealed that species of Penicillium, Cladosporium, Aspergillus, Fusarium, Beauveria, and Trichoderma were present. The latter two species were the result of the application of biocontrol products for control of insects and diseases, respectively. Fungal communities present in unpasteurized coconut (coco) fiber growing medium are potential sources of mold contamination on cannabis plants. Swabs taken from greenhouse-grown and indoor buds pre- and post-harvest revealed the presence of Cladosporium and up to five species of Penicillium, as well as low levels of Alternaria species. Mechanical trimming of buds caused an increase in the frequency of Penicillium species, presumably by providing entry points through wounds or spreading endophytes from pith tissues. Aerial distribution of pathogen inoculum and mold spores and dissemination through vegetative propagation are important methods of spread, and entry through wound sites on roots, stems, and bud tissues facilitates pathogen establishment on cannabis plants.

Cannabis use is an emergent risk factor for periodontitis, a chronic bacterial-induced disease of the supporting structures of the teeth. However, the mechanisms by which marijuana exposure predisposes to periodontal tissue destruction have yet to be elucidated. Therefore, we examined the influence of physiologically relevant doses of major marijuana-derived phytocannabinoid subtypes (cannabidiol [CBD]; cannabinol [CBN]; and tetrahydrocannabinol [THC], 1.0 μg/ml) on the interactions of three ultrastructurally variant oral pathogens, Porphyromonas gingivalis, Filifactor alocis, and Treponema denticola with the immune system. CBD, CBN, and THC each suppressed P. gingivalis-induced IL-12 p40, IL-6, IL-8, and TNF release while enhancing the anti-inflammatory cytokine, IL-10, from human innate cells. Similar phenomena were observed in F. alocis- and T. denticola-exposed human monocytes and human gingival keratinocytes. Higher phytocannabinoid doses (≥5.0 μg/ml) compromised innate cell viability and inhibited the growth of P. gingivalis and F. alocis, relative to unexposed bacteria. T. denticola, however, was resistant to all cannabinoid doses tested (up to 10.0 μg/ml). Pharmaceutical inhibition and efficient gene silencing indicated that a common CB2/PI3K axis of immune suppression is triggered by phytocannabinoids in vitro. This pathway does not appear to perpetuate through the canonical GSK3β-dependent cholinergic anti-inflammatory pathway, the predominant endogenous inflammatory control system. In a repetitive, transient oral infection model, CBD also suppressed P. gingivalis-induced innate immune markers in wild-type mice, but not in CB2-/- mice. If such phenomena occur in humans in situ, environmental cannabinoids may enhance periodontitis via direct toxic effects on specific oral bacteria; by compromising innate cell vitality; and/or through a suppressed innate response to periodontal pathogens involving a CB2/PI3K signaling lineage.

Impulsivity and risk-taking are known to have an important impact on problematic substance use and criminal behavior. This study examined the predictive value of baseline self-report and behavioral impulsivity and risk-taking measures [Delay Discounting Task (DDT), Balloon Analogue Risk Task (BART) and Behavioral Inhibition, Behavioral Activation Scale (BIS/BAS)] in 12-months follow-up substance use outcomes (e.g., use of alcohol, cannabis and other substances) and criminal recidivism (yes/no). Participants were 213 male offenders with a substance use disorder (SUD) under probation supervision. Bivariate regression analyses showed that BIS and BAS levels were associated (respectively) with the use of alcohol and cannabis. Multiple regression analysis showed that BIS was negatively associated with alcohol use at follow-up, whereas cannabis use at baseline and BAS predicted cannabis use at follow-up. At a trend level, interactions between delay discounting and risk-taking, and interactions between baseline cannabis use and BAS and BART predicted cannabis use at follow-up. Other substance use at follow-up was solely predicted by baseline other substance use. Overall, the findings provide marginal support for the predictive utility of impulsivity and risk-taking in accounting for variability in substance use among offenders with a SUD. This may be partly explained by the fact that only a limited number of psychological factors was assessed in this study. The studied population consists of a severe group, in which relapse into substance use or criminal behavior likely is related to complex, interacting biopsychosocial factors, of which impulsivity measures play a relatively small part.

Recent years have seen substantial shifts in cultural attitudes towards cannabis for medical and recreational use. However, legalizing recreational marijuana may have adverse effects on individual and public health. As the most widely used illicit agent, cannabis is commonly reported to disrupt learning and memory. Unfortunately, the molecular mechanisms underlying behavioral impairment by cannabis abuse remain poorly understood. Tetrahydrocannabinol (THC), a major component in cannabis, causes short-term effects on the visual system, but little is known about persisting visual disturbances. This study was to investigate the effects of systemic administration with THC on retina and explore its underlying mechanisms. BALB/c mice were treated with 1 or 2 mg/kg THC intraperitoneally daily for 2 months, mice treated with vehicle as negative control. The retinal function was tested by electroretinography after THC treatment. Morphology and pathology changes of retina were detected by hematoxylin and eosin staining. Terminal deoxynucleotidyl transferase dUTP nick end labeling assay was used to detect the apoptosis in photoreceptor cells. Enzyme-linked immunosorbent assay was used to show the inflammatory responses and oxidative stress. mRNA and protein changes were measured by real-time polymerase chain reaction and Western blot to explore the underlying mechanisms. Results indicated that 2-month treatment with THC caused retinal damage, evidenced by its functional loss and increased apoptosis in photoreceptor cells through inducing inflammatory responses and oxidative stress. Our study demonstrated that systemic administration with THC caused toxic effects on retinas of BALB/c mice, suggesting the potential mechanisms for the retina damage caused by cannabis abuse.

Pesticide residue analysis in cannabis has become a subject of growing interest in North America since recent legalization in Canada and decriminalization for medicinal or recreational use in most US states. To meet regulatory and quality control standards, cannabis products should be tested for both authorized and unauthorized pesticides. In Canada, testing requirements mandated by Health Canada stipulate pesticide contaminant limits of quantification values of 0.02-3.0 μg/g, 0.01-2.5 μg/g and 0.01-1.5 μg/g for cannabis dried flowers, oil and fresh plants, respectively. Sample preparation and clean up methods reported in the literature for pesticide analysis in cannabis products include liquid-liquid extraction, solid-phase extraction, solid-phase microextraction and QuEChERS whereas separation and detection methods include thin-layer chromatography, capillary electrophoresis, high-performance liquid chromatography and gas chromatography in combination with various detectors such as UV and mass spectrometers. Advantages and disadvantages of the various analytical methods used in pesticide analysis of cannabis products are evaluated in this review. Furthermore, challenges ahead and future directions are discussed.

Juvenile drug treatment courts (JDTCs) were established in the 1990s to reduce the cycle of crime, drug use, and delinquency among youthful offenders. The principles and guidelines underlying JDTCs, roles of multidisciplinary team members, and procedures common to JDTCs are described. Youth served by JDTCs are frequently male, identify as racial or ethnic minorities, come from impoverished backgrounds, and experience significant psychiatric comorbidity. This article reviews the small number of clinical trials that have examined adjunctive treatments using family-based and individual behavioral treatment approaches designed to improve the overall efficacy of JDTCs. Considerations for future research on JDTCs are described.

Cannabis continues to be the most widely used illicit substance among youth, as many teens view the risks of cannabis consumption to be low. With cannabis laws becoming lax and dispensaries becoming more prevalent throughout the United States, highly concentrated Δ-9-tetrahydrocannibinol (THC) is becoming readily available. This article examines the available literature on consumption of concentrated THC, focusing on potential consequences of concentrate use among youth. Various methods for consuming concentrated THC, including ingestion of edibles, vaping, and dabbing, are discussed, along with associated risks of each consumption method. Recommendations for health professionals are provided.

As an increasing number of states legalize cannabis use for recreational and/or medical purposes, it is increasingly important to understand the neural and cognitive consequences of recreational cannabis use in adolescent consumers. Adolescence is marked by ongoing neuromaturational processes, making this a particularly vulnerable period, particularly regarding exposure to drugs, including cannabis. This review highlights evidence from studies documenting the neural impact of cannabis use in adolescence and explores mediating factors related to cannabis use.

Canada implemented 'plain packaging' regulations and rotating health warnings for cannabis products upon legalizing non-medical cannabis in October 2018. Plain packaging and health warnings are effective policy measures for reducing appeal of tobacco products; however, there is little evidence in the cannabis domain.An experimental task was conducted as part of the online International Cannabis Policy Study. Participants aged 16-65 from Canada (n = 9987) and US states with 'legal' (n = 7376) and 'illegal' (n = 9682) recreational cannabis were randomly assigned to see one of 18 cannabis product images. Outcomes were product appeal (0 = Not at all appealing, 10 = Very appealing) and perceived youth orientation (4 age groups). A 3 (branding: full branding, brand logo only, or plain black packaging) x 2 (health warning labels: present or absent) x 3 (product type: edible gummies, cannabis oil, or pre-rolled joints) factorial design was used.Compared to plain packaging or a brand logo, packages with full branding were considered more appealing and more likely to be youth-oriented (p < 0.001). Products with health warnings were considered less appealing than packages without warnings (p < 0.001). Edible gummies were perceived as more appealing and more likely to be youth-oriented than pre-rolled joints and cannabis oil (p < 0.001). Additionally, edible gummies were rated as significantly more appealing by 16-18 and 19-35-year-olds than by older adults (p < 0.02 for all).Comprehensive health warnings and 'plain packaging' regulations may reduce the appeal of cannabis products in a legal market. The results also provide empirical evidence that edible gummies are perceived to appeal to youth.

Although driving under the influence of cannabis is increasingly common among young adults, little is known about residual effects on driver behavior. This study examined acute and residual effects of smoked cannabis on simulated driving performance of young cannabis users.In this double-blind, placebo-controlled, parallel-group randomized clinical trial, cannabis users (1-4 days/week) aged 19-25 years were randomized with a 2:1 allocation ratio to receive active (12.5% THC) or placebo (0.009% THC) cannabis in a single 750 mg cigarette. A median split (based on whole-blood THC concentrations at the time of driving) was used to divide the active group into low and high THC groups. Our primary outcome was simulated driving performance, assessed 30 min and 24 and 48 h after smoking. Secondary outcomes included blood THC concentrations, subjective drug effects, and heart rate.Ninety-six participants were randomized, and 91 were included in the final analysis (30 high THC, 31 low THC, 30 placebo). Mean speed (but not lateral control) significantly differed between groups 30 min after smoking cannabis (p ≤ 0.02); low and high THC groups decreased their speed compared to placebo. Heart rate, VAS drug effect and drug high increased significantly immediately after smoking cannabis and declined steadily after that. There was little evidence of residual effects in any of the measures.Acutely, cannabis caused decreased speed, increased heart rate, and increases in VAS drug effect and drug high. There was no evidence of residual effects on these measures over the two days following cannabis administration.

Cannabis is commonly used for its medical properties. In particular, cannabis is purported to have beneficial effects on a wide range of neuropsychiatric conditions. Studies assessing mental health in cannabis dispensary users typically evaluate symptoms using self-report check lists, which provide limited information about symptom severity, and whether subjects meet criteria for a psychiatric diagnosis. There is, therefore, a need for studies which assess mental health in dispensary users with standardized and well validated scientific instruments, such as those used in clinical drug trials.One hundred medical cannabis users were recruited from a community dispensary. All subjects completed a structured clinical interview with the Mini-International Neuropsychiatric Interview (MINI). Subjects also completed the Perceived Stress Scale-10, PROMIS Fatigue Scale, PROMIS Sleep Disturbance Scale, Beck Depression Inventory, the Patient Health Questionnaire-15 and the Brief Pain Inventory. Details about cannabis use were also recorded.Lifetime prevalence of mental illness in this cohort was high, and a large proportion of subjects endorsed psychological symptoms. The proportion of subjects who met criteria for classification of a current psychiatric disorder was low for mood disorders, but high for anxiety disorders and substance abuse/dependence. Cannabis use differed between the main psychiatric conditions.The present results indicate that rates of mental illness may be high in medical cannabis dispensary users. Use of structured clinical assessments combined with standardized symptom severity questionnaires provide a feasible way to provide a more rigorous and detailed evaluation of conditions and symptoms in this population.

Objective: The objective of this study was to use electroencephalogram (EEG) biomarkers derived from a short, easily administered neurocognitive testbed to determine acute cannabis intoxication and its effect on driving performance in a driving simulator.Methods: The data analyzed were from a study examining the relationship between psychomotor task performance, EEG data, and driving performance in a simulator. EEG data were collected using a STAT® X-24 EEG Wireless Sensor Headset, which was worn during the psychomotor and driving tasks. Driving data were collected for segments of consistent driving environments, including urban driving, urban curves, interstate, interstate curves, dark rural, and rural straightaways. Dependent measures included measures of lateral and longitudinal vehicle control.Results: There was a significant relationship between impaired driving performance as indicated by increased standard deviation of lane position and EEG power in slow theta band (3-5 Hz) in parietal and occipital areas.Conclusions: These results, combined with our prior reported results, suggest that EEG and electrocardiogram (ECG) acquired concurrent with neuropsychological tests hold potential to provide a highly sensitive, specific, and dose-dependent profile of cannabis intoxication and level of impairment.

Objective: The objective of this study was to compare the variability in vehicle control for sober young adult drivers (18-23 years old) who either use cannabis but are not acutely exposed or do not use cannabis.Methods: The data analyzed in the study were from 4 prospective driving simulation studies (completed at the National Advanced Driving Simulator at the University of Iowa) that examined vehicle control metrics in cannabis users and nonusers across high-fidelity simulated urban, interstate, and rural driving environments. Data were collected for segments of consistent driving environments including urban driving, urban curves, interstate, interstate curves, dark rural, and rural straight. Dependent measures included measures of lateral and longitudinal vehicle control.Results: Thirty out of 72 (12 users and 18 nonusers) met the age requirements for inclusion in the analysis. Between the cohorts, we identified differences in lateral and longitudinal driving performance. For lateral control there were no observed effects on variability in lane keeping. Cannabis users exhibited lower frequency steering and fewer and less variable steering reversals compared to nonusers. For longitudinal control, cannabis users drove slower than nonusers and more accelerator pedal holds and a lower accelerator pedal reversal rate were observed.Conclusions: Young adult drivers who use cannabis in our study drove slower and produced significantly less frequent steering and accelerator pedal inputs than drivers who did not use cannabis. This suggests that lasting effects of cannabis use persist and may lead to detrimental driving behaviors even after intoxication has subsided. These findings have implications for legislation in support of legalizing cannabis because sober cannabis-using drivers may still be a public health concern. Further study is needed to evaluate whether these differences persist even with longer term abstinence and whether differences are found in other age demographics.

Medicinal cannabinoids, including medicinal cannabis and pharmaceutical cannabinoids and their synthetic derivatives, such as tetrahydrocannabinol (THC) and cannabidiol (CBD), have been suggested to have a therapeutic role in certain mental disorders. We analysed the available evidence to ascertain the effectiveness and safety of all types of medicinal cannabinoids in treating symptoms of various mental disorders.For this systematic review and meta-analysis we searched MEDLINE, Embase, PsycINFO, the Cochrane Central Register of Controlled Clinical Trials, and the Cochrane Database of Systematic Reviews for studies published between Jan 1, 1980, and April 30, 2018. We also searched for unpublished or ongoing studies on ClinicalTrials.gov, the EU Clinical Trials Register, and the Australian and New Zealand Clinical Trials Registry. We considered all studies examining any type and formulation of a medicinal cannabinoid in adults (≥18 years) for treating depression, anxiety, attention-deficit hyperactivity disorder (ADHD), Tourette syndrome, post-traumatic stress disorder, or psychosis, either as the primary condition or secondary to other medical conditions. We placed no restrictions on language, publication status, or study type (ie, both experimental and observational study designs were included). Primary outcomes were remission from and changes in symptoms of these mental disorders. The safety of medicinal cannabinoids for these mental disorders was also examined. Evidence from randomised controlled trials was synthesised as odds ratios (ORs) for disorder remission, adverse events, and withdrawals and as standardised mean differences (SMDs) for change in symptoms, via random-effects meta-analyses. The quality of the evidence was assessed with the Cochrane risk of bias tool and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. This study is registered with PROSPERO (CRD42017059372, CRD42017059373, CRD42017059376, CRD42017064996, and CRD42018102977).83 eligible studies (40 randomised controlled trials, n=3067) were included: 42 for depression (23 randomised controlled trials; n=2551), 31 for anxiety (17 randomised controlled trials; n=605), eight for Tourette syndrome (two randomised controlled trials; n=36), three for ADHD (one randomised controlled trial; n=30), 12 for post-traumatic stress disorder (one randomised controlled trial; n=10), and 11 for psychosis (six randomised controlled trials; n=281). Pharmaceutical THC (with or without CBD) improved anxiety symptoms among individuals with other medical conditions (primarily chronic non-cancer pain and multiple sclerosis; SMD -0·25 [95% CI -0·49 to -0·01]; seven studies; n=252), although the evidence GRADE was very low. Pharmaceutical THC (with or without CBD) worsened negative symptoms of psychosis in a single study (SMD 0·36 [95% CI 0·10 to 0·62]; n=24). Pharmaceutical THC (with or without CBD) did not significantly affect any other primary outcomes for the mental disorders examined but did increase the number of people who had adverse events (OR 1·99 [95% CI 1·20 to 3·29]; ten studies; n=1495) and withdrawals due to adverse events (2·78 [1·59 to 4·86]; 11 studies; n=1621) compared with placebo across all mental disorders examined. Few randomised controlled trials examined the role of pharmaceutical CBD or medicinal cannabis.There is scarce evidence to suggest that cannabinoids improve depressive disorders and symptoms, anxiety disorders, attention-deficit hyperactivity disorder, Tourette syndrome, post-traumatic stress disorder, or psychosis. There is very low quality evidence that pharmaceutical THC (with or without CBD) leads to a small improvement in symptoms of anxiety among individuals with other medical conditions. There remains insufficient evidence to provide guidance on the use of cannabinoids for treating mental disorders within a regulatory framework. Further high-quality studies directly examining the effect of cannabinoids on treating mental disorders are needed.Therapeutic Goods Administration, Australia; Commonwealth Department of Health, Australia; Australian National Health and Medical Research Council; and US National Institutes of Health.

Over the past two decades, a growing cadre of US states has legalized the drug commonly known as "marijuana." But even as more states legalize the drug, proponents of reform have begun to shun the term "marijuana" in favor of the term "cannabis." Arguing that the "M" word has been tainted and may thus dampen public support for legalization, policy advocates have championed "cannabis" as an alternative and more neutral name for the drug. Importantly, however, no one has tested whether calling the drug "cannabis" as opposed to "marijuana" actually has any effect on public opinion. Using an original survey experiment, we examine whether framing the drug as "marijuana" as opposed to "cannabis" shapes public attitudes across a range of related topics: support for legalization of the drug, moral acceptance of its use, tolerance of activities involving the drug, perceptions of the drug's harms, and stereotypes of its users. Throughout each of our tests, we find no evidence to suggest that the public distinguishes between the terms "marijuana" and "cannabis." We conclude with implications of our findings for debates over marijuana/cannabis policy and for framing in policy discourse more generally.

Despite research advances, it remains unclear if long-term, regular cannabis use harms cognition once intoxication has passed. Our meta-analysis aimed to investigate the association between cognitive functioning and long-term (mean ≥2 years), regular (mean ≥4 days/week), recreational cannabis use in adults during abstinence (mean ≥12 hr). We searched PubMed, PsycINFO, CINAHL, Scopus, and Dissertations and Theses International for English-language articles from the date each database began until May 22, 2019. We identified study inclusion by completing abstract and full text screening using predetermined criteria and Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. We classified cognitive performance into 6 cognitive domains (attention, executive function, learning and memory, decision making, information processing, and working memory), and included a global measure. Effect sizes were calculated for each domain using univariate meta-analyses. There were 30 studies with a total 849 participants who used cannabis (M = 30.7-years-old, SD = 5.5-years-old) and 764 control participants (M = 30.3-years-old, SD = 5.9-years-old). Cannabis was associated with significant but small-magnitude deficits in executive function, learning and memory, and global cognition, while decision making had moderate deficits. There were small-magnitude and nonsignificant group differences for information processing, working memory, and attention. Cannabis use duration, age of onset, and prolonged abstinence (≥25 days) did not influence outcomes, except group differences in executive function were nonsignificant in analyses of prolonged abstinence. Our results suggest that long-term, regular cannabis use is associated with small to moderate deficits in some cognitive domains. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

With the increasing consumption of hemp seed products, it is important to establish whether biological samples from consumers contain trace cannabinoids that could mistakenly be attributed to cannabis abuse. Thus, we analyzed whether the cannabinoids, 11-nor-9-carboxy-tetrahydrocannabinol, cannabidiol, and cannabinol, can be detected in the urine of short-term (1 week) and long-term (12 weeks) consumers of hemp seed products. Using three hemp seed products that have recently been highly distributed in Korea, subjects consumed 30 g of hemp seeds (Group A, 53.1 (±0.5) μg THC and Group B, 124.81 (±1.5) μg THC) or 2 capsules of hemp seed oil (Group C, 11.1 μg THC) once a day at 10am. In the short-term study, the hemp seed product was consumed for 7 days, after which a single urine sample was collected. In the long-term study, the hemp seed product was consumed for 12 weeks, and urine samples were collected at 7 day intervals. For screening of the urine samples, we used COBAS C311, and for the confirmatory analysis we used gas chromatography/mass spectrometry. In the screening, all 64 samples from the short-term study were below the detection cutoff level of 25 ng/mL. In the long-term study, out of the 480 samples, 3 samples from 2 participants were above the cutoff level, but these samples were all negative in screening. In conclusion, our study demonstrated that when hemp seed products sold in Korea are consumed in normal quantities over the short- or long-term, urine samples do not test positive for cannabinoids.

Medical cannabis is increasingly used for the treatment of various ailments in children and adults. Three major cannabinoids in cannabis are delta-9-tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabinol (CBN). There is a growing need to develop and utilize a patient-centric blood microsampling methodology to enable clinical trials and facilitate therapeutic drug monitoring. We have employed the volumetric absorptive microsampling (VAMS™) devices that enables accurate and precise collection of a fixed volume (20 µL) of blood, minimizing the impact of hematocriton accurate quantitation. We developed an ultra-performance liquid chromatographic method with tandem mass spectrometry detection for the quantification of three cannabinoids (THC, CBD, and CBN) employing deuterium labelled internal standards (THC-D3, CBD-D3, and CBN-D3). Sample extraction of VAMS™ devices, followed by solid phase extraction, reverse phase chromatographic separation, and selective detection using tandem mass spectrometry with a 6-minute runtime per sample was developed. Standard curves were linear between 1 and 500 ng/mL for THC and 0.5-500 ng/mL for CBD and CBN. Intra-day accuracies were within 91.3-112% while inter-day accuracies were within 94.4-107% with both having precisions (CV (%)) of <13% based on quality control samples in a three day validation study for all three cannabinoids. Analytes were stable in human whole blood under assay conditions (60 h at room temperature and 24 h in autosampler post-extraction). Dried microsamples were stable for one week at 40 °C, two weeks (15 days) under different storage conditions (room temperature, 4, -20 and -78 °C), one month (29 days) at -20 and -78 °C and three months (68 days) at -78 °C. This assay provides an efficient quantitation of THC, CBD, and CBN in VAMS™ devices and is currently being implemented for pediatric clinical trials.

Despite the rise in heroin use in sub Saharan-Africa opioid agonist maintenance treatment (OAMT) is still not state-funded in South Africa and many other African countries. In South Africa there has been little data published on the profile of heroin users and the outcomes of treatment for those who attend public treatment services.300 heroin users from two state-funded rehabilitation centres in Johannesburg were studied at entry into rehabilitation and 3-months after treatment. Treatment consisted of inpatient detoxification and inpatient psychosocial rehabilitation. Structured interviews measured changes in drug use, psychopathology and criminality post rehabilitation.Most (65.7%) smoked heroin in combination with cannabis while 29.7% were injecting users. Almost half the sample (49.3%) had at least one mental illness. Of the 252 (84%) participants seen at 3-month follow-up, 6.3% were abstinent of all substances (excluding tobacco), 65.5% had continued heroin use (CHU) and the balance used other substances. At follow-up there were significant decreases in heroin use (p<0.0001) and criminality (p<0.0001). There were however significant increases in alcohol use (p<0.0001), crystalmetamphetamine use (p=0.032) and the prevalence of current episode of major depression (p<0.0001). Just 11.9% received formal psychosocial treatment after leaving rehabilitation. None were on OAMT and only three participants were on psychotropic medication. None were tested for Hepatitis C during the study period and the majority (53%) did not know their HIV status.There are significant gaps in current treatment services for heroin users in South Africa. Retention in treatment and assessment and management of psychiatric and non-psychiatric comorbidities is low. Services need to be more integrated and should also include the provision of OAMT.

With the growing acceptance of cannabis use, it is crucial to understand the drug's effects on episodic memory accuracy and distortion. We investigated the impact of the administration of Δ9-tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis, on a context-based memory illusion.In a double-blind, placebo-controlled, within-subjects design, healthy infrequent cannabis users (N = 24) memorized object pictures that were superimposed over scenes (e.g., gray cat on beach) after pretreatment with placebo or THC (15 mg oral). Two days later under sober conditions, memory for the object pictures was tested by asking participants to discriminate between previously seen objects or perceptually similar lures (e.g., different gray cat). Context reinstatement was manipulated by presenting objects on their original or different scenes (e.g., beach or forest).THC impaired memory for perceptual details of objects compared with placebo, and the context illusion was obtained in each condition: context reinstatement increased high-confidence false recognition along with correct recognition of previously seen objects. Although THC did not interact with these context effects overall, post hoc analyses showed that THC magnified the context illusion when objects were semantically congruent with their encoding contexts but abolished the context illusion when objects were incongruent with their encoding contexts.These results are consistent with the hypothesis that THC impairs the encoding of specific object information more than item-context associations. As a result, THC may spare the distorting effects of context reinstatement on memory. In fact, THC may increase these distorting effects under conditions when objects are semantically congruent with context.

Hypercholesterolemia (HC) is a major risk factor for cardiovascular (CV) diseases, that are the major cause of mortality worldwide. Free radicals mediated oxidative stress is a critical player in HC-associated pathophysiological insults including atherosclerosis. Unwanted side effects associated with statins, COX-2 inhibitors, and other synthetic drugs limit their use. Thus, modulation of oxidative stress during HC using green pharmaceuticals seems an appropriate approach against deleterious CV consequences without noticeable side-effect. In this regard, owing to an abundance of proteins, fiber and optimal ratios of omega 6 PUFA: omega-3 PUFA in Hempseed (HS), we aim to exploit its anti-inflammatory and antioxidant properties to ameliorate HC- associated CV effects.Comparing the antioxidant capacity of protein and lipid fractions of HS using ABTS and DPPH assays, HS was supplemented to high-fat diets (HFD) induced hypercholesterolemic wistar rats. After treatment schedules, lipid profiles, histological and ultrastructural investigations, gene and protein expressions of inflammatory markers, markers of oxidative stress were studied and correlated with biophysical parameters such as ECG and impedance/conductance across the aorta. HS demonstrating in vitro free radical scavenging activity, ameliorated the signs of HC as seen with improved lipid profiles, aortic tissue damage and ECG patterns compared to HFD groups. HS administration also relieved the COX-2 mediated inflammation, which correlated well with the improved redox status in the tissue.Current study evidently demonstrates that the anti-hypercholesterolemic effects of HS are mediated through redox-sensitive modulation of inflammatory pathways.

The core symptoms and co-morbidities associated with autism spectrum disorders (ASD) affect daily living and quality of life. Existing pharmacological interventions are only able to attenuate some related symptoms but are unable to address the underlying etiologies associated with ASD. Anecdotal evidence, which claims benefit from the use of cannabis to treat symptoms among this population, has been gaining popularity as families seek solutions.This paper analyzed recent peer-reviewed literature to identify the current state of evidence regarding cannabis use for the ASD population. Systematic reviews, reports, and experimental studies were assessed to understand the current extent and nature of the evidence on the risks and benefits of cannabis use for ASD. At this time, three large-scale clinical trials are currently at varying stages of progress and publication of results. Only five small studies were identified that have specifically examined cannabis use in ASD. Given the sparse state of evidence directly assessed in this population, studies which examined effects of cannabis on shared pathological symptoms of ASD such as hyperactivity, sleep disorders, self-injury, anxiety, behavioral problems, and communication were also reviewed.Studies revealed mixed and inconclusive findings of cannabis effects for all conditions, except epilepsy. Adverse outcomes were also reported, which included severe psychosis, increased agitation, somnolence, decreased appetite, and irritability. In addition, a wide range of cannabis compositions and dosage were identified within the studies, which impact generalizability.There is currently insufficient evidence for cannabis use in ASD, which creates an urgent need for additional large-scale controlled studies to increase understanding of risks and benefits and also to examine the impact of "entourage effects." This will support discussions of treatment options between health care providers and ASD patients and their families. Evidence may lead to a desired new line of treatment or prevent adverse outcomes from unsubstantiated use amongst families aiming for symptom reduction.

The aim of the current study was to examine the prevalence and associations of hazardous alcohol use with sociodemographic variables and its comorbidity with depression and other common mental disorders in a sample of Greek adolescents between 16 and 18 year old.We recruited 2431 adolescents attending 25 senior high schools in Greece. We assessed depressive and anxiety disorders using the computerized version of a fully-structured psychiatric interview (the revised Clinical Interview Schedule / CIS-R). Alcohol use was assessed using questions taken from a previous WHO school survey.Approximately one-third of adolescents (overall: 30.7%, boys: 39.2%, girls: 21.9%, p < 0.001) consumed alcohol on a weekly basis. The experience of excessive consumption, leading to drunkenness at least two or more times in their lifetime, was reported by 15.39% of the adolescents (19.42% for the boys and 11.24% for the girls, p < 0.001). Frequent alcohol consumption and drunkenness were strongly associated with the presence of depression, all other anxiety disorders except panic disorder, current smoking, and lifetime cannabis use, lower school performance, bad or fair relationship with parents, and increased health services use.Alcohol use is highly prevalent among Greek adolescents. Special attention for the development of more focused preventive strategies should be paid to adolescents suffering from depression or other common mental disorders.

Women who use psychoactive substances could have higher levels of unplanned pregnancy and of difficulties accessing long-term contraceptive methods than those who do not use these substances. General population data on this topic are rare, particularly in France.This study is based on data from the French Health Survey 2016, collected from women aged 15 to 49 years and living in the Great Paris region (N=1626). Use of illegal psychoactive substances (cannabis, substances used via intranasal or intravenous administration) were evaluated over the lifecourse and, for cannabis, over the 12 months preceding the study. Unplanned pregnancies were ascertained over the preceding 5 years, emergency contraception, abortion, and the experience of sexual violence during the lifecourse. We also studied the number of sexual partners in the preceding 12 months, as well as current contraception. Data were analyzed using weighted logistic regression models, adjusted for participants' sociodemographic characteristics and tobacco use.Women who use illegal substances have a higher probability than non-users to experience an unplanned pregnancy in the preceding 5 years (OR associated with lifecourse cannabis use: 1.61, 95% CI 1.00-2.58), to have used emergency contraception (ORs between 2.20 to 2.90), to have had an abortion (OR associated with lifecourse cannabis use: 1.77, 95% CI 1.26-2.49), and to have experienced sexual violence (ORs between 1.87 to 3.14). They also had more sexual partners than non-users, but did not differ in terms of contraception.In the general population, there is a relationship between women's use of illegal substances and their probability of experiencing sexual violence. These results should be brought to the attention of health professionals in contact with women, to help identify those who have addictive behaviors and identify their sexual and reproductive health needs.

Evidence for an association between cannabis and psychosis has been documented in literature in many forms including experimental studies, epidemiological data, and case series. The association has implications for psychotic outcomes ranging from mild to severe and occurring over minutes to years. Due to the huge variety of exposures and outcome measures reported, creating a coherent account of all the available information is difficult. A useful way to conceptualize these wide-ranging results is to consider the association between cannabis and psychosis as it occurs within the context of widely used DSM-5 diagnoses. In the present review we examine cannabis/psychosis associations as they pertain to Cannabis Intoxication, Cannabis-Induced Psychotic Disorder, and Schizophrenia. This allows for an understanding of the cannabis and psychosis association along something approaching a continuum. Cannabis intoxication becomes Cannabis-Induced Psychotic Disorder once certain severity and duration criteria are met and Cannabis-Induced Psychotic Disorder is heavily associated with future schizophrenia diagnoses.

Authentication of Cannabis products is important for assuring the quality of manufacturing, with the increasing consumption and regulation. In this report, a two-stage pipeline was developed for high-throughput screening and chemotyping the spectra from two sets of botanical extracts from the Cannabis genus. The first set contains different marijuana samples with higher concentrations of tetrahydrocannabinol (THC). The other set includes samples from hemp, a variety of Cannabis sativa with the THC concentration below 0.3%. The first stage applies the technique of class modeling to determine whether spectra belong to marijuana or hemp and reject novel spectra that may be neither marijuana nor hemp. An automatic soft independent modeling of class analogy (aSIMCA) that self-optimizes the number of principal components and the decision threshold is utilized in the first pipeline process to achieve excellent efficiency and efficacy. Once these spectra are recognized by aSIMCA as marijuana or hemp, they are then routed to the appropriate classifiers in the second stage for chemotyping the spectra, i.e., identifying these spectra into different chemotypes so that the pharmacological properties and cultivars of the spectra can be recognized. Three multivariate classifiers, a fuzzy rule building expert system (FuRES), super partial least-squares-discriminant analysis (sPLS-DA), and support vector machine tree type entropy (SVMtreeH), are employed for chemotyping. The discriminant ability of the pipeline was evaluated with different spectral data sets of these two groups of botanical samples, including proton nuclear magnetic resonance, mass, and ultraviolet spectra. All evaluations gave good results with accuracies greater than 95%, which demonstrated promising application of the pipeline for automated high-throughput screening and chemotyping marijuana and hemp, as well as other botanical products.

The associations between low educational attainment and substance use disorders (SUDs) may be related to a common genetic vulnerability. We aimed to elucidate the associations between polygenic scores for educational attainment and clinical criterion counts for three SUDs (alcohol, nicotine and cannabis).Polygenic association and sibling comparison methods. The latter strengthens inferences in observational research by controlling for confounding factors that differ between families.Six sites in the United States.European ancestry participants aged 25 years and older from the Collaborative Study on the Genetics of Alcoholism (COGA). Polygenic association analyses included 5582 (54% female) participants. Sibling comparisons included 3098 (52% female) participants from 1226 sibling groups nested within the overall sample.Outcomes included criterion counts for DSM-5 alcohol use disorder (AUDSX), Fagerström nicotine dependence (NDSX) and DSM-5 cannabis use disorder (CUDSX). We derived polygenic scores for educational attainment (EduYears-GPS) using summary statistics from a large (> 1 million) genome-wide association study of educational attainment.In polygenic association analyses, higher EduYears-GPS predicted lower AUDSX, NDSX and CUDSX [P < 0.01, effect sizes (R2 ) ranging from 0.30 to 1.84%]. These effects were robust in sibling comparisons, where sibling differences in EduYears-GPS predicted all three SUDs (P < 0.05, R2 0.13-0.20%).Individuals who carry more alleles associated with educational attainment tend to meet fewer clinical criteria for alcohol, nicotine and cannabis use disorders, and these effects are robust to rigorous controls for potentially confounding factors that differ between families (e.g. socio-economic status, urban-rural residency and parental education).

The majority of states have legalized medical marijuana (MM) despite its Federal Schedule 1 designation as an illegal substance. Public schools must comply with Drug Free Workplace laws or risk the loss of federal funding. To address the conflict between state and federal laws regulating MM, the National Association of School Nurses issued a position brief in January 2019. The accompanying article introduces the Cannabis/Marijuana Position Brief and provides guidance for school nurses who encounter a student treated with MM. Topics addressed include background implications of federal marijuana and hemp law, mechanism of action for MM, Epidiolex overview, current research regarding efficacy of MM for common qualifying conditions, and implications for school nursing practice.

Prostate cancer patients receiving androgen-deprivation therapy (ADT) often experience a combination of disease symptoms and treatment side effects. The therapeutic use of cannabis to alleviate these side effects has not been studied, despite increasing patient interest. With the increasing availability of cannabis, it is important for clinicians to understand the prevalence, predictors, and perceived benefits of cannabis use among patients with prostate cancer.A total of 222 men undergoing ADT were assessed in this two-part study. In part one, the cannabis-use questionnaire was administered to 56 men, probing demographics, usage habits, perspectives, and degrees of symptom relief related to cannabis use. In part two, 191 cryopreserved urine samples were retrieved and analyzed for the presence of tetrahydrocannabidiol (THC) metabolite 11-nor-Δ9-THC-COOH. The respondents were then stratified into two groups, users vs. non-users, and statistical analyses were conducted.Questionnaire data revealed that 23.2% of surveyed men had recently used cannabis. In contrast, 5.8% of men had detectable levels of THC metabolite in their urine. Combined questionnaire and urine data revealed that cannabis users were significantly younger (p=0.003) and had lower testosterone levels (p=0.003) than non-users. The majority of men experiencing common ADT side effects reported some degree of relief following cannabis use.Cannabis use among men with advanced prostate cancer receiving ADT is more prevalent than in the general population and the majority of other oncological cohorts. Lower testosterone levels and reported therapeutic benefit among cannabis users warrants confirmation in appropriate clinical trials.

We assess the current and describe possible future public health impacts of the legalisation of cannabis production, sale, and use in the Americas. First, we describe global patterns of cannabis use and their most probable adverse health effects. Second, we summarise evidence regarding the effectiveness of cannabinoids for medicinal use and describe approaches that have been used to regulate the use of medicinal cannabis and how these approaches might have affected medicinal and recreational use and harms (eg, road crashes). Third, we describe how jurisdictions that have legalised recreational use have regulated production and sale of cannabis. Fourth, we evaluate the effects of cannabis legalisation on cannabis use and harms and on the use of alcohol, tobacco, and other drugs. Fifth, we use alcohol and tobacco policy examples to identify possible long-term public health effects of cannabis legalisation. Finally, we outline policy approaches that could minimise harms to public health arising from the legalisation of a commercial cannabis industry.

The symptomatic treatment of myotonia and myalgia in patients with dystrophic and non-dystrophic myotonias is often not satisfactory. Some patients anecdotally report symptoms' relief through consumption of cannabis.A combination of cannabidiol and tetrahydrocannabinol (CBD/THC) was prescribed as compassionate use to six patients (four patients with myotonic dystrophy types 1 and 2, and 2 patients with CLCN1-myotonia) with therapy-resistant myotonia and myalgia. CBD/THC oil was administered on a low dose in the first 2 weeks and adjusted to a higher dose in the following 2 weeks. Myotonia behaviour scale (MBS), hand-opening time, visual analogue scales (VAS) for myalgia and myotonia, and fatigue and daytime sleepiness severity scale (FSS, ESS) were performed weekly to monitor treatment response.All patients reported an improvement of myotonia especially in weeks 3 and 4 of treatment: MBS improved of at least 2 points in all patients, the hand-opening time variously improved in 5 out of 6 patients. Chronic myalgia was reported by both DM2 patients at baseline, one of them experienced a significant improvement of myalgia under treatment. Some gastrointestinal complaints, as abdominal pain and diarrhoea, improved in 3 patients; however, 4 out of 6 patients reported new-onset constipation. No other relevant side effect was noticed.These first empirical results suggest a potentially beneficial role of CBD/THC in alleviating myotonia and should encourage further research in this field including a randomized-controlled trial on larger cohorts.

Cannabis use in pediatric health care remains limited, however, there is increasing evidence on the pharmacologic benefits of medical marijuana for chronic conditions in childhood. Realizing the need for guidance in practice, the National Council of State Boards of Nursing (NCSBN) published guidelines to aid in decision making in nursing practice. While focusing primarily on adult use of cannabis, the guidelines do address special populations such as children and adolescents. This article reviews the endocannabinoid system, current state of legislation on medical marijuana, policy considerations, recent FDA approval of a cannabis product for pediatric use, NCSBN National Nursing Guidelines for Medical Marijuana, and pediatric implications for nursing practice.

Soft independent modeling of class analogy (SIMCA) is an important method for authentication. The key parameters for SIMCA, the number of principal components and the decision threshold, determine the model's performance. In this report, a self-optimizing SIMCA that automatically determines these two parameters is devised and referred to as automatic SIMCA (aSIMCA). An efficient optimization is obtained by incorporating response surface modeling (RSM) and bootstrapped Latin partitions with the model-building dataset. A set of design points over the ranges of the two parameters are evaluated with respect to sensitivity and specificity by using the model-building data from target and non-target classes. Averages of the sensitivity and specificity are used as responses for the design points. A 2-dimensional interpolation and a bivariate cubic polynomial were used to model the response surface. As a control method, a grid search that evaluates all combinations of the two parameters over the same ranges was performed in parallel to determine the best conditions for SIMCA and the modeling performance was compared to aSIMCA with RSM. The developed aSIMCA methods were evaluated by authenticating two botanical extracts sets, i.e., marijuana and hemp, with spectral datasets collected from various spectroscopic techniques, including nuclear magnetic resonance, high-resolution mass, and ultraviolet spectrometry. Results of a paired t-test indicated that the aSIMCA with the RSM had similar performance with the one optimized by the grid search for modeling marijuana and hemp, while the RSM was more computationally efficient. The 2-dimensional interpolation is preferred because the better efficiency and the fit to the response surface is more precise.

Cannabis usage is increasing with its widespread legalization. Cannabis use by mothers during lactation transfers active cannabinoids to the developing offspring during this critical period and alters postnatal neurodevelopment. A key neurodevelopmental landmark is the excitatory to inhibitory gamma-aminobutyric acid (GABA) switch caused by reciprocal changes in expression ratios of the K+/Cl- transporters potassium-chloride cotransporter 2 (KCC2) and sodium-potassium-chloride transporter (NKCC1).Rat dams were treated with Δ9-tetrahydrocannabinol or a synthetic cannabinoid during the first 10 days of postnatal development, and experiments were then conducted in the offspring exposed to these drugs via lactation. The network influence of GABA transmission was analyzed using cell-attached recordings. KCC2 and NKCC1 levels were determined using Western blot and quantitative polymerase chain reaction analyses. Ultrasonic vocalization and homing behavioral experiments were carried out at relevant time points.Treating rat dams with cannabinoids during early lactation retards transcriptional upregulation and expression of KCC2, thereby delaying the GABA switch in pups of both sexes. This perturbed trajectory was corrected by the NKCC1 antagonist bumetanide and accompanied by alterations in ultrasonic vocalization without changes in homing behavior. Neurobehavioral deficits were prevented by CB1 receptor antagonism during maternal exposure, showing that the CB1 receptor underlies the cannabinoid-induced alterations.These results reveal how perinatal cannabinoid exposure retards an early milestone of development, delaying the trajectory of GABA's polarity transition and altering early-life communication.

Opioids are frequently prescribed for the management of patients with chronic non-cancer pain (CNCP). Previous meta-analyses of efficacy and harms have combined treatment effects across all opioids; however, specific opioids, pharmacokinetic properties (ie, long acting vs short acting), or the type of formulation (ie, immediate vs extended release) may be a source of heterogeneity for pooled effects.We will conduct a network meta-analysis (NMA) of randomized controlled trials evaluating opioids for CNCP. We will acquire eligible studies through systematic searches of EMBASE, MEDLINE, CINAHL, AMED, PsycINFO, and the Cochrane Central Registry of Controlled Trials (CENTRAL). Eligible studies will have randomly allocated adult CNCP patients to an oral or transdermal opioid versus another type of opioid (or formulation) or placebo, and follow patients for ≥ 4 weeks. We will collect outcome data for pain intensity, physical function, nausea, vomiting, and constipation. Pairs of reviewers will, independently and in duplicate, abstract data from eligible trials and assess risk of bias using a modified Cochrane tool. We will assess coherence of our networks through both a global test, and by comparing direct and indirect evidence for each comparison with node-splitting.Using a frequentist approach, we will conduct random effects multiple treatment meta-analysis to establish treatment effects of individual opioids for each outcome. The certainty of evidence for pooled treatment effects will be assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. We will categorize interventions from most to least effective based on the effect estimates obtained from NMAs and their associated certainty of evidence, as follows: superior to both placebo and alternatives; superior to placebo, but inferior to alternatives; and no better than placebo.This NMA will determine the relative effectiveness and adverse effects of individual opioids among patients with CNCP. Our results will help inform the appropriateness of assuming similar beneficial and adverse effects of varying opioid formulations.This systematic review is registered with Prospective Register of Systematic Reviews, an international prospective register of systematic reviews (registration no.: CRD42018110331), available at https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=110331.

Aim Cannabis is the most widely used illegal drug in Ireland. We sought to describe the changing pattern of cannabis use and cannabis related health harms. Methods Data was collated from two national population surveys and three national treatment databases, focusing on people under 34 years. Results Past month cannabis use among adolescents and young adults increased after 2011, coinciding with a decline in perceived risk of regular use. The prevalence estimate for cannabis dependence increased from 1.1% to 3.6% from 2011 to 2015. From 2008 to 2016, there were increases in the rates of cannabis related addiction treatment episodes among adolescents and among young adults of 40% and 168% respectively. Cannabis related admissions to general and psychiatric hospitals increased by 90% and 185% respectively. Conclusion A concerted public health response is required to address escalating cannabis related health harms which have coincided with the arrival of more potent cannabis.

Drug addiction causes chronic wounds (CW) responsible for severe complications. Very few studies are available on this topic. The aim of our study was to describe the demographic, clinical and etiological characteristics as well as the course of CW in drug addicts.This was a retrospective and prospective multicenter study including all drug addicts with CW.We included 58 patients (17 prospectively), 84.5% of whom were male, of median age 43 years, presenting multiple CW as a result of intravenous (78.2%), inhaled (41.1%) and/or snorted (20%) drug abuse. Addiction to opioids (68.4%), cocaine (47.4%) and/or cannabis (40.4%) was ended and/or treated through substitution in 79.3% of patients. CW were fibrinous and necrotic (42.9 to 53.6%), recurrent (54.2%), and in some cases had been present for more than 1 year (61.5%). Intravenous drug addiction was associated with large, fibrinous, ulcers in a setting of venous and lymphatic insufficiency (74%). Only 23% of these wounds involved the upper limbs. Necrotic ulcers associated with clinical arteriopathy were described mainly with inhaled addiction. Abscesses (50%) and erysipelas (29.3%) were the most common cutaneous complications. After 3 months, 50% of CW were improved and 29.2% of patients were lost to follow-up.Drug abuse-related CW occurred preferentially in young men with history of intravenous abuse. For the most part, CW were seen on the legs and were associated with venous and lymphatic insufficiency, and the resulting major risk for cutaneous infection increased morbidity and mortality in this population in whom medical follow-up is inherently complicated.

Purpose: Cannabis is the most prevalent drug in the world and its consumption is growing. Cannabinoid receptors are present in the human central nervous system. Recent studies show evidence of the effects of cannabinoids on the retina, and synthesising the results of these studies may be relevant for ophthalmologists. Thus, this review adopts standardised, systematic review methodology to investigate the effects of exposure to cannabis and components on the retina.Methods: We searched five online databases for the combined terms for outcome ("retina") and exposure ("cannabis"). Eligibility of studies were conducted by two independent reviewers, and risk of bias was assessed.Results: We retrieved 495 studies, screened 229 studies, assessed 52 studies for eligibility, and included 16 studies for qualitative analysis. The cannabinoids most frequently investigated were delta-9-tetrahydrocannabinol (THC), abnormal cannabidiol, synthetic cannabinoid, and cannabidiol (CDB). The outcomes most studied were neuroretinal dysfunction, followed by vascular effects. The studies also included investigation of neuroprotective and anti-inflammatory effects and teratogenic effects.Conclusions: This review suggests that cannabinoids may have an important role in retinal processing and function.