Implementation and Preliminary Evaluation of a 12-Week Cognitive Behavioural and Motivational Enhancement Group Therapy for Cannabis Use Disorder.

Background: The purpose of this paper is to provide a preliminary evaluation of treatment outcomes, retention and client satisfaction following a 12-week combined cognitive behavioural therapy (CBT) and motivational enhancement therapy (MET) group treatment for cannabis use disorder (CUD) delivered in an outpatient setting. Implementation of the program is also described. Methods: A retrospective observational cohort study was conducted using data collected from medical records and self-report assessments. Participants were treatment-seeking cannabis users at the Centre for Addiction and Mental Health, Toronto. Cannabis use, cannabis-related problems, craving, withdrawal symptoms, self-efficacy for remaining abstinent, depression and anxiety were assessed pre- and post-treatment. Treatment retention was calculated by inspecting clinic attendance records, and client satisfaction was evaluated using an anonymous feedback survey. Potential predictors of treatment outcomes and retention were investigated in exploratory analyses. Results: Cannabis use was lower and days of abstinence higher post-treatment (vs pre-treatment). Post-treatment improvements in cannabis-related problems, craving, withdrawal symptoms, self-efficacy and mood were also observed. Completion of group treatment (⩾75% of sessions attended) was 57% and moderate levels of treatment satisfaction were reported. Conclusions: This study provides preliminary evidence that a 12-week combined CBT and MET treatment for cannabis use disorder delivered in a novel group setting improves cannabis use outcomes. Potential predictors of reduced cannabis use and retention were identified. Future controlled studies are warranted, and strategies for increasing retention should be explored.

Sex Differences in the Neuropsychiatric Effects and Pharmacokinetics of Cannabidiol: A Scoping Review.

Cannabidiol (CBD) is a non-intoxicating cannabinoid compound with diverse molecular targets and potential therapeutic effects, including effects relevant to the treatment of psychiatric disorders. In this scoping review, we sought to determine the extent to which sex and gender have been considered as potential moderators of the neuropsychiatric effects and pharmacokinetics of CBD. In this case, 300 articles were screened, retrieved from searches in PubMed/Medline, Scopus, Google Scholar, PsycInfo and CINAHL, though only 12 met our eligibility criteria: eight studies in preclinical models and four studies in humans. Among the preclinical studies, three suggested that sex may influence long-term effects of gestational or adolescent exposure to CBD; two found no impact of sex on CBD modulation of addiction-relevant effects of Δ9-tetrahydrocannabinol (THC); two found antidepressant-like effects of CBD in males only; and one found greater plasma and liver CBD concentrations in females compared to males. Among the human studies, two found no sex difference in CBD pharmacokinetics in patient samples, one found greater plasma CBD concentrations in healthy females compared to males, and one found no evidence of sex differences in the effects of CBD on responses to trauma recall in patients with post-traumatic stress disorder (PTSD). No studies were identified that considered the role of gender in CBD treatment effects. We discuss potential implications and current limitations of the existing literature.

Comparing immediate- and delayed-onset posttraumatic stress disorder: Results from the National Epidemiologic Survey on Alcohol and Related Conditions-III (NESARC-III).

Delayed-onset posttraumatic stress disorder (PTSD) is defined as a period of 6 months or more between trauma exposure and episode onset. Due to the limited research and lack of epidemiological studies on this form of the disorder, we investigated its prevalence, clinical features, and psychiatric comorbidities in a nationally representative sample of U.S. adults. Using National Epidemiologic Survey on Alcohol and Related Conditions-III (NESARC-III) data collected from individuals who met the DSM-5 criteria for PTSD (N = 1,980), we compared delayed- and immediate-onset PTSD with regard to demographic and clinical variables, including comorbidity with psychiatric and substance use disorder (SUD) diagnoses. The overall prevalence of delayed-onset PTSD was 11.0%. Respondents with delayed-onset PTSD were more likely than those with immediate-onset PTSD to report active military combat exposure, more physical and emotional difficulties, and higher levels of pain; these individuals were also more likely to be divorced and less likely to meet the diagnostic criteria for select SUDs. After adjusting for confounding variables, we found a decreased risk of delayed-onset PTSD among individuals with hallucinogen use disorder, OR = 0.30; 95% CI [0.11, 0.87], d = 0.5. We found no significant associations between PTSD onset status and any other SUD, including alcohol use disorder, after adjusting for covariates. Further longitudinal research is required to investigate the temporal associations between PTSD onset and its clinical characteristics and comorbidities, as this could have implications on disorder progression and treatment approaches.

Mu opioid receptor gene variant modulates subjective response to smoked cannabis.

The mu-opioid receptor (MOR) mediates the rewarding properties of many psychoactive drugs and is an important target in the treatment of addictions. Functional interactions between the opioid and endocannabinoid systems are established and have been hypothesized to contribute to the effects of cannabis. We investigated associations between three single nucleotide polymorphisms in the MOR gene OPRM1 (rs1799971, rs2281617, and rs510769) and subjective responses to smoked cannabis. Fifty-two regular cannabis users (1-4 days/week) were given a cannabis cigarette (12.5% THC) and rated their subjective responses on visual analog scales at baseline and at multiple time points after smoking. Blood samples were collected for THC quantification. There was a significant impact of the intronic variant rs510769 on subjective cannabis effects and THC blood levels. The influence of this gene variant may thus be mediated by pharmacodynamics and/or pharmacokinetic factors. We provide novel evidence that variability in OPRM1 contributes to individual responses to cannabis and may affect risk of cannabis use disorder. Our findings add to the growing body of literature on the genetic basis of individual responses to cannabis and may have implications for targeting the endogenous opioid system in the treatment of cannabis use disorder.

Potential of Fatty Acid Amide Hydrolase (FAAH), Monoacylglycerol Lipase (MAGL), and Diacylglycerol Lipase (DAGL) Enzymes as Targets for Obesity Treatment: A Narrative Review.

The endocannabinoid system (ECS) plays an integral role in maintaining metabolic homeostasis and may affect hunger, caloric intake, and nutrient absorption. Obesity has been associated with higher levels of the endogenous cannabinoid transmitters (endocannabinoids). Therefore, the ECS is an important target in obesity treatment. Modulating the enzymes that synthesize and degrade endocannabinoids, namely fatty acid amide hydrolase (FAAH), monoacylglycerol lipase (MAGL), and diacylglycerol lipase (DAGL), may be a promising strategy to treat obesity. This review aims to synthesize all studies investigating pharmacological or genetic manipulation of FAAH, MAGL, or DAGL enzymes in association with obesity-related measures. Pharmacological inhibition or genetic deletion of FAAH tended to promote an obesogenic state in animal models, though the relationships between human FAAH polymorphisms and obesity-related outcomes were heterogeneous, which could be due to FAAH having both pro-appetitive and anti-appetitive substrates. Genetic deletion of Mgll and Dagla as well as pharmacological inhibition of DAGL tended to reduce body weight and improve metabolic state in animal studies, though the effects of Mgll manipulation were tissue-dependent. Monitoring changes in body weight in ongoing clinical trials of FAAH inhibitors may clarify whether FAAH inhibition is a potential therapeutic strategy for treatment obesity. More preclinical work is needed to characterize the role of MAGL and DAGL modulation in obesity-related outcomes.

Multiple Substance Use Disorders and Self-Reported Cognitive Function in U.S. Adults: Associations and Sex-Differences in a Nationally Representative Sample.

Polysubstance use is a growing public health concern that has been associated with poor clinical outcomes. Compared to single-drug users, this population suffers greater deficits in cognitive function, which hinder treatment success and recovery. Despite its high prevalence and poor prognosis, epidemiological research on polysubstance use and accompanying cognitive profile is lacking. We investigated associations between numbers of past-year co-occurring substance use disorders (SUDs) and self-reported cognitive function using data from the National Epidemiologic Survey for Alcohol and Related Conditions III (NESARC-III). Regression analyses revealed a significant negative association between cognitive scores and numbers of past-year SUDs, which was moderated by sex. After adjusting for confounding variables, greater numbers of SUDs were associated with declining self-reported cognitive function, and this relationship was stronger among females. Our findings expand on current literature on cognitive impairments among polysubstance users and provide a novel, nuanced description of this relationship among the general population. We highlight the need for targeted and individualized treatment approaches in order to improve outcomes in this population.