Varenicline reduced cannabis use in men with cannabis use disorder but not in women

Varenicline did not reduce cannabis use sessions overall during weeks 6-12. However, a significant treatment-by-sex interaction revealed that men on varenicline reduced their cannabis use sessions significantly (difference = 4.2 sessions/week), while women showed no benefit.

Phase 2, randomized, double-blind, placebo-controlled trial at two South Carolina clinics (2020-2023). 174 participants with DSM-5 cannabis use disorder who used cannabis at least 3 days/week were randomized to varenicline (titrated to 1 mg twice daily) or placebo for 12 weeks with weekly medical management.

There are no FDA-approved medications for cannabis use disorder. This trial adds to a small but growing body of evidence that biological sex may determine which pharmacological treatments work, a finding that could reshape how CUD medications are developed and tested.

The sex-specific finding mirrors patterns seen in nicotine research, where varenicline also shows variable effects. This raises the question of whether CUD treatment development has been missing important signals by not routinely analyzing results by sex.

Relatively small sample when split by sex, reducing power for subgroup analyses. Single geographic region. The sex interaction was not a pre-specified primary analysis. Self-reported cannabis use.