Cannabidiol may help reduce cannabis use
Cannabidiol appeared safe and more effective than placebo at lowering cannabis use, according to results of a randomized clinical trial published in The Lancet Psychiatry.
“Cannabidiol has generated substantial interest because of its potential medicinal uses and ability to interact with the effects of THC,” Tom P. Freeman, PhD, of the Addiction and Mental Health Group at University of Bath in the U.K., and colleagues wrote. “Cannabidiol has shown therapeutic effects in humans and preclinical models of addiction by reducing the effect of drug-related cues in attentional bias, cue-induced craving and cue-induced reinstatement paradigms. Collectively, these studies suggest that cannabidiol has potential for treating a range of substance use disorders, including cannabis, opioids and tobacco.”
Although results of a meta-analysis of randomized clinical trials suggested cannabidiol was safe and well-tolerated, as well as associated with few adverse effects, it may interact with other medications and should thus be carefully monitored because of its potential role in inhibiting cytochrome P450 enzymes, according to the researchers. To their knowledge, no randomized trials have evaluated cannabidiol as a potential treatment for cannabis use disorder.
In the current study, Freeman and colleagues sought to pinpoint efficacious doses and eliminate inefficacious doses in a phase 2a trial that used an adaptive Bayesian design. In the trial’s first stage, they randomly assigned 48 participants who met DSM-5 criteria for cannabis use disorder to 4-week treatment with three different oral cannabidiol doses — 200 mg, 400 mg or 800 mg — or with matched placebo during a cessation attempt. Participants underwent a brief psychological intervention involving motivational interviewing.
In the trial’s second stage, a new set of 34 participants received either placebo or doses deemed efficacious in the interim analysis. The investigators’ primary objective was to identify the cannabidiol dost that was most efficacious for reducing cannabis use. Lower urinary 11-nor-9-carboxy-delta-tetrahydrocannabinol (THC-COOH):creatinine ratio, increased days per week with cannabis abstinence during treatment or both served as primary endpoints.
Results at final analysis showed cannabidiol 400 mg and 800 mg exceeded both primary outcomes’ primary endpoint criteria. The likelihood of urinary THC-COOH:creatinine being the most efficacious dose vs. placebo given the observed data was 0.9995 for cannabidiol 400 mg and 0.9965 for cannabidiol 800 mg. The likelihood for days with cannabis abstinence of being the most efficacious dose vs. placebo given the observed data was 0.9966 for cannabidiol 400 mg and 0.9247 for cannabidiol 800 mg. Cannabidiol 400 mg lowered THC-COOH:creatinine ratio by –94·21 ng/mL and increased cannabis abstinence by 0.48 days per week compared with placebo. Cannabidiol 800 mg lowered THC-COOH:creatinine ratio by –72·02 ng/mL and increased cannabis abstinence by 0.27 days per week compared with placebo. Moreover, cannabidiol was well-tolerated and was not associated with severe adverse events. A total of 77 (94%) of 82 participants completed treatment.
“Our trial provides the first causal evidence supporting cannabidiol as a treatment for cannabis use disorders,” Freeman and colleagues wrote. “These findings are important in light of major policy changes surrounding the production and sale of cannabis products, increases in the number of people entering treatment for cannabis use disorders worldwide and the absence of recommended pharmacotherapies at present.”