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

The takeaway

A 12-week trial of varenicline (a smoking cessation drug) found no overall effect on cannabis use, but men showed a significant reduction while women did not.

Addiction medicine clinicians, CUD treatment researchers, pharmacotherapy developers

4.2 fewer cannabis sessions per week in men on varenicline vs. placebo

What the researchers found

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.

Why it matters

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 numbers in context

174 participants randomized (90 varenicline, 84 placebo). No overall treatment effect (difference = 1.7 sessions/week, p = 0.41). Significant sex interaction (F = 5.1, p = 0.026). Men: 4.2 fewer sessions/week (95% CI 0.6-7.8, p = 0.04). Women: no effect (difference = -1.4, p = 0.18).

How the study worked

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.

What this study cannot tell us

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.

How to read the evidence

Well-designed Phase 2 RCT with double-blinding and placebo control, though the sex-specific finding was not the primary endpoint and sample size was modest for subgroup analysis.

When this study was published

2026 publication reporting on trial conducted 2020-2023

The bigger picture

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.

Questions still open

Why might varenicline work differently in men and women for cannabis use? Would a larger trial powered specifically for sex differences confirm this finding? Could dosing adjustments change outcomes for women?

Common questions

What is varenicline?

Varenicline (brand name Chantix) is a medication approved for smoking cessation. It works on nicotinic acetylcholine receptors, which also interact with brain reward pathways involved in cannabis use.

Could this become a treatment for cannabis addiction?

Possibly for men, but the finding needs replication in a larger trial designed to test sex differences as a primary outcome.

Read the original research

Varenicline for cannabis use disorder: A randomized controlled trial.

Addiction (Abingdon, England)

View on PubMed ↗Publisher’s paper ↗

Citation

McRae-Clark, Aimee L; Gray, Kevin M; Baker, Nathaniel L; Sherman, Brian J; Tolliver, Bryan; Burt, Jessica; Steplight, Alonzo; Chapman, Elizabeth; Wagner, Amanda. (2026). Varenicline for cannabis use disorder: A randomized controlled trial.. Addiction (Abingdon, England). https://doi.org/10.1111/add.70296