Animal studies and human clinical trials have found a potential new drug that could facilitate the treatment of cannabis addiction. The results were published recently in the journal Nature Medicine. The findings, based on data from animal models and phase 1 and 2a clinical trials, demonstrate that a newly developed inhibitor of the cannabinoid receptor (CB1) reduces cannabis’ effects without triggering withdrawal symptoms.
Cannabis is the most widely used illicit drug in the world, and 19.5% of those who have used cannabis develop a cannabis use disorder (CUD). Cannabis use disorder is characterised by persistent impairment, such as failing to attend to work or personal obligations, continuing to use cannabis despite problems, and an inability to cut down its use. Despite this public health concern, there are currently no treatments for cannabis use disorder.
Previous research has shown that activation of the cannabinoid receptor by tetrahydrocannabinol (THC) — the main psychoactive component of cannabis — is responsible for the behavioural effects of cannabis. Pier Vincenzo Piazza from Aelis Farma, Bordeaux, France and the corresponding author of the study and colleagues developed a new drug that targets a mechanism that inhibits a subset of the molecular pathways activated by the cannabinoid receptor. The authors report data from preclinical proof-of-concept studies demonstrating that the drug inhibited THC’s behavioural effects without disrupting normal behaviour or physiological activities in mice and non-human primates. They also report results from two phase 1 clinical trials, conducted in 64 healthy human volunteers, that show the drug to be safe and well tolerated. The authors ran a phase 2a crossover trial that involved 29 participants with CUD who received one of two different doses of the drug in one five-day phase and placebo in another five-day phase in randomised order. The results indicate that the drug decreased ratings of cannabis’ positive subjective effects and decreased cannabis self-administration relative to placebo, without triggering cannabis withdrawal or disrupting normal functions (such as mood, sleep, food intake) over a five-day period.
These findings suggest that the drug under investigation may have the potential to be used for treating cannabis use disorder without substantial side effects. The authors, however, note that further trials are needed in larger cohorts to determine the long-term safety and efficacy of the intervention and that a three-month study in patients seeking treatment for cannabis use disorder CUD is currently under way.
