Effects of cannabidiol on anandamide levels in individuals with cannabis use disorder: findings from a randomised clinical trial for the treatment of cannabis use disorder.

Cannabidiol (CBD) has shown promise in treating psychiatric disorders, including cannabis use disorder - a major public health burden with no approved pharmacotherapies. However, the mechanisms through which CBD acts are poorly understood. One potential mechanism of CBD is increasing levels of anandamide, which has been implicated in psychiatric disorders including depression and cannabis use disorder. However, there is a lack of placebo-controlled human trials investigating this in psychiatric disorders. We therefore assessed whether CBD affects plasma anandamide levels compared to placebo, within a randomised clinical trial of CBD for the treatment of cannabis use disorder. Individuals meeting criteria for cannabis use disorder and attempting cannabis cessation were randomised to 28-day administration with placebo (n = 23), 400 mg CBD/day (n = 24) or 800 mg CBD/day (n = 23). We estimated the effects of each CBD dose compared to placebo on anandamide levels from baseline to day 28. Analyses were conducted both unadjusted and adjusted for cannabis use during the trial to account for effects of cannabis on the endocannabinoid system. We also investigated whether changes in plasma anandamide levels were associated with clinical outcomes relevant for cannabis use disorder (cannabis use, withdrawal, anxiety, depression). There was an effect of 800 mg CBD compared to placebo on anandamide levels from baseline to day 28 after adjusting for cannabis use. Pairwise comparisons indicated that anandamide levels unexpectedly reduced from baseline to day 28 in the placebo group (-0.048, 95% CI [-0.089, -0.007]), but did not change in the 800 mg CBD group (0.005, 95% CI [-0.036, 0.047]). There was no evidence for an effect of 400 mg CBD compared to placebo. Changes in anandamide levels were not associated with clinical outcomes. In conclusion, this study found preliminary evidence that 28-day treatment with CBD modulates anandamide levels in individuals with cannabis use disorder at doses of 800 mg/day but not 400 mg/day compared to placebo.

Cannabis and cannabidiol use among autistic and non-autistic adults in the UK: a propensity score-matched analysis.

OBJECTIVES: To assess whether autistic and non-autistic adults differ in their cannabis and cannabidiol (CBD) use, their perceptions of cannabinoid products and their cannabinoid-related support-seeking behaviours. DESIGN: Cross-sectional survey. PARTICIPANTS: Respondents to an online survey, who self-reported an autism-spectrum disorder diagnosis (autistic participants) or no issues relating to autism (controls). Exclusion criteria were: related/subclinical issues relating to autism, non-UK residence, under 16 years old. Propensity score matching was used to match autistic participants and controls on age, gender and ethnicity. The full-sample analysis included 269 participants and the propensity-matched sample analysis included 166 participants. Propensity-matched analysis was used for primary analysis and was considered robust if supported by triangulation with full-sample analysis. RESULTS: Autistic participants were more likely to have used CBD in the past 12 months compared with controls (OR=3.52, 95% CI 1.57 to 7.87, p=0.002). They used CBD on more days in the past 12 months (M=34, SD=93) compared with controls (M=17, SD=69, p=0.002). Autistic participants reported trusting the news and doctors less as sources of cannabinoid-related information than controls (p=0.024 and p=0.003, respectively). Autistic participants endorsed the following barriers to cannabinoid-related support seeking more than controls: 'worrying they won't understand me' (OR=3.25, 95% CI 1.67 to 6.33, p<0.001), 'going somewhere unfamiliar' (OR=5.29, 95% CI 2.62 to 10.67, p<0.001) and 'being in a crowded or chaotic place' (OR=9.79, 95% CI 4.18 to 22.89, p<0.001). CONCLUSION: Results indicate a higher prevalence and frequency of CBD use, but not cannabis use, among autistic individuals compared with controls. Findings also suggest appropriate methods to disseminate cannabinoid-related support to autistic individuals, and indicate differences in the potential barriers autistic and non-autistic individuals may face when seeking cannabinoid-related support.