For patients with cannabis use disorder, cannabidiol (CBD) slightly reduced use in a phase II trial.
In a group of 82 patients with moderate to severe cannabis use, urinary 11-nor-9-carboxy-δ-9-tetrahydrocannabinol (THC-COOH):creatinine ratio declined by 94.21 ng/mL (95% interval estimate –161.83 to –35.56) for those given 400 mg CBD daily, reported Tom Freeman, PhD, of the University of Bath in England, and colleagues in The Lancet Psychiatry.
The CBD group also remained abstinent for 0.48 more days per week (95% interval estimate 0.15-0.82) compared with placebo at 4 weeks.
An 800-mg dose also decreased the THC-COOH creatinine ratio significantly (–72.02 ng/mL, 95% interval estimate –135.47 to –19.52). Abstinence from cannabis was not significantly increased, however (0.27 days per week, 95% interval estimate –0.09 to 0.64), compared with placebo.
Both doses were safe, with no serious adverse events recorded and no significant differences in the rate of other events in the placebo and either treatment arm, the researchers added. The most common side effect was migraine, which occurred in four and two patients in the 400-mg and 800-mg CBD groups, respectively.
“The effects of the cannabidiol doses tested are suggestive of an inverted-U dose-response curve,” Freeman and co-authors wrote. “From a treatment perspective, our findings indicate that cannabidiol doses ranging from 400 mg to 800 mg have the potential to reduce cannabis use in clinical settings, and that additional benefit is unlikely to be gained from doses exceeding 800 mg.”
Current treatment for cannabis use disorder, also known as marijuana use disorder, is limited to behavioral therapy. However, researchers are studying whether sleep medications such as zolpidem (Ambien) or anxiolytics like buspirone (BuSpar) can mitigate marijuana withdrawal, according to the National Institute on Drug Abuse.
Early phase trials have shown positive signals that certain pharmacologic agents could play a role in the treatment of cannabis use disorder, including naltrexone and long-acting fatty acid amide hydrolase inhibitors. CBD has also been associated with craving and anxiety reductions related to other addictions, such as heroin use disorder.
“CBD likely works through a completely different mechanism than THC and its effects are likely indirect and more complex than we know at the moment,” commented Ryan McLaughlin, PhD, of Washington State University in Pullman.
For example, some in vitro studies have indicated that CBD could influence the binding sites of THC — the psychoactive component of cannabis — making it less of a “good fit,” explained McLaughlin, who was not involved in this research.
The trial involved patients ages 16-60 who met diagnostic criteria for cannabis use disorder, confirmed with a urine drug screen, who wanted to quit in the next month but had failed to quit at least once. Pregnant or breastfeeding women were excluded, as were non-English speakers. All patients smoked tobacco with cannabis before enrollment.
Participants came in weekly during treatment, were followed up by telephone, and reminded by text messages to take their medication twice daily. All patients also received six 30-minute motivational interviewing sessions with psychologists.
Although the reductions in use observed in this study were relatively small, even participants in the placebo group went from having 1 to 2 days of abstinence per week at baseline to around 4 days of abstinence per week in the trial, commented Andrew J. Saxon, MD, of the University of Washington in Seattle, and also not involved in the trial.
“Thus, it seems that the behavioral intervention is having some impact and more than what the medication has,” Saxon told MedPage Today in an email.
The first stage of the trial evaluated a 200-mg CBD dose, but its efficacy was minimal, so patients originally randomized to this arm were reassigned.
Patients in the placebo group were slightly younger on average (age 25) than patients in the 400- or 800-mg CBD arms (age 27), the authors reported. Overall, the cohort included more than 70% males and had close to nine symptoms of cannabis use disorder symptoms at baseline.
Although the 400-mg CBD arm was associated with reduced urinary THC-COOH:creatinine and increased abstinence compared with placebo through the trial’s end at 12 weeks, the 800-mg treatment arm was similar to placebo in both outcomes after this longer follow-up, Freeman and co-authors reported.
Compared with placebo, 400-mg CBD also decreased the number of cigarettes smoked per week at 4 weeks and 12 weeks, although patients in this treatment group reported poorer sleep than those in the placebo group, the researchers noted. In addition, for patients on the 800-mg CBD dose, withdrawal and anxiety symptoms improved compared with placebo at 4 and 12 weeks.
The trial was not designed to show the magnitude of efficacy for CBD and has a relatively short treatment period, which are limitations, the authors wrote, adding that food consumption or other factors may play a role in CBD’s bioavailability.
The study was funded by the UK Medical Research Council Developmental Pathway Funding Scheme award and the Society for the Study of Addiction.
Freeman reported having no competing interests; one co-author reported receiving funding from Spectrum Therapeutics.