Media release

From: Springer Nature

A potential drug to target cannabis addiction

A potential new drug that could facilitate the treatment of cannabis addiction is reported in 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). CUD is characterized 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 CUD.

Previous research has shown that activation of the CB1 receptor by tetrahydrocannabinol (THC) — the main psychoactive component of cannabis — is responsible for the behavioral effects of cannabis. Pier Vincenzo Piazza and colleagues developed a new drug, AEF0117, that targets a mechanism that inhibits a subset of the molecular pathways activated by the CB1 receptor. The authors report data from preclinical proof-of-concept studies demonstrating that the drug inhibited THC’s behavioral effects without disrupting normal behavior 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 AEF0117 in one 5-day phase and placebo in another 5-day phase in randomized order. The results indicate that AEF0117 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 5-day period.

These findings identify AEF0117 as a potential drug to be used for treating CUD without substantial side effects. The authors note that further trials are needed in larger cohorts to determine the long-term safety and efficacy of AEF0117, and that a 3-month study in patients seeking treatment for CUD is ongoing.