Grant: Project Grant

Canada has the highest age-standardized incidence of cannabis addiction in the world. At present, there are no effective pharmacotherapies for cannabis use disorder (CUD). Recent evidence suggests that semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist used for weight loss, has anti-addiction properties. In studies from the U.S. and Sweden, users of semaglutide were less likely to experience opioid overdose or hospitizations for any substance use disorder. In patients with a prior history of CUD, use of semaglutide for obesity substantially reduced the risk of a recurrent CUD diagnosis compared to other anti-obesity medication. However, to date no trials have investigated whether semaglutide can be used to treat patients with CUD. We will recruit 104 participants with CUD and heavy cannabis use for a double-blind randomized controlled trial. Participants will be randomized to treatment with semaglutide or placebo over a 16 week period. The dose of semaglutide will be titrated according to the semaglutide dose escalation schedule for diabetes treatment; participants will be treated with 0.25mg/week from weeks 1-4, then 0.5mg/week from weeks 5-8, then 1.0mg/week from weeks 9-12, and then 2.0 mg per week from weeks 13-16. The primary outcome is treatment efficacy, measured by change in self-reported cannabis use and the levels of a quantitative urinary biomarker of cannabis use over treatment. We hypothesize that participants randomized to semaglutide will demonstrate evidence of reduced cannabis use over the course of treatment compared to placebo. Our secondary outcomes include cardiometabolic changes (e.g., weight loss), changes in cannabis use 2 months following discontinuation of the medication, and changes in quality of life over treatment. There are currently high rates of CUD in Canada and no effective pharmacotherapies for this condition; this trial could pave the way for semaglutide to become the first evidence-based pharmacotherapy for CUD.