Semaglutide and Cannabis Use Disorder: What the Data Shows

A major study of 680,000+ patients found striking associations between semaglutide use and reduced cannabis use disorder. Here's what the numbers actually say.

The Study: Molecular Psychiatry, March 2024

Researchers from Case Western Reserve University and the National Institute on Drug Abuse analyzed electronic health records from over 680,000 patients across 61 U.S. healthcare organizations. They compared cannabis use disorder (CUD) outcomes in people taking semaglutide versus those on other obesity or diabetes medications.

The study was published in Molecular Psychiatry, one of the top-ranked psychiatry journals.

The Numbers

Study Design Details

Who Was Studied

• 85,223 patients with obesity — prescribed semaglutide or other anti-obesity medications (bupropion, naltrexone, orlistat, topiramate, phentermine)
• 596,045 patients with type 2 diabetes — prescribed semaglutide or other non-GLP-1 anti-diabetes medications

What They Measured

The researchers tracked two outcomes over 12 months:

• Incident CUD — new diagnosis of cannabis use disorder (ICD-10 code F12) in people with no prior history
• Recurrent CUD — return of CUD diagnosis in people who had been diagnosed before

How They Controlled for Confounders

The study used propensity score matching to balance the groups on factors like age, sex, race, BMI, and comorbidities. This reduces (but doesn't eliminate) the risk that observed differences are due to something other than semaglutide.

Why This Matters: No Approved Treatments Exist

Cannabis is the most frequently used illicit drug in the United States — over 45 million users annually. About one-third of regular users develop cannabis use disorder (CUD). Despite this prevalence:

• Zero FDA-approved medications for CUD
• Current treatment relies entirely on behavioral therapy
• Relapse rates remain high

If semaglutide truly reduces CUD risk, it would represent a major breakthrough — the first pharmacological option for a condition affecting millions.

"What's exciting about GLP-1 receptor agonist medications is their potential to treat addiction more broadly, meaning they may be able to treat different kinds of addictive disorders." — Nora Volkow, MD, Director of NIDA, study co-author

The Mechanism: Why It Might Work

Cannabis activates the endocannabinoid system, but its rewarding effects ultimately depend on dopamine release in the nucleus accumbens — the same pathway involved in other addictions.

GLP-1 receptors are expressed in reward-related brain regions. When activated by semaglutide, they appear to:

• Reduce dopamine release in response to rewarding stimuli
• Dampen the subjective "high" from drugs
• Decrease motivation to seek drugs

Interestingly, cannabinoid receptors (CB1R) and GLP-1 receptors are both present in the lateral habenula — a brain region involved in aversion and avoidance. This overlap could be relevant to how semaglutide affects cannabis use.

Limitations: What This Study Can't Tell Us

The authors themselves emphasize caution:

"While this study shows the potential of semaglutide to treat cannabis use disorders, this is a retrospective study with many inherent limitations." — Rong Xu, PhD, Case Western Reserve University, study co-author

Key limitations include:

• Observational, not causal — we can't prove semaglutide caused the reduced CUD risk
• Medical record data — dependent on diagnosis coding, which can be incomplete
• Selection bias — people prescribed semaglutide may differ from controls in unmeasured ways
• No cannabis use data — the study tracked diagnoses, not actual cannabis consumption
• 12-month follow-up only — we don't know if effects persist longer term

What Comes Next

The researchers call for:

• Preclinical studies — to understand the mechanism
• Randomized clinical trials — to establish causation
• Longer follow-up — to assess durability of any effect

As of December 2024, no clinical trials specifically studying semaglutide for cannabis use disorder are registered on ClinicalTrials.gov. Given the positive observational data, this may change.

Should You Try Semaglutide for Cannabis Use?

The data is intriguing but not actionable yet:

• No FDA approval — GLP-1s aren't indicated for CUD
• Insurance won't cover it — off-label use is expensive
• Unproven in RCTs — observational data isn't the same as evidence it works
• Side effects are real — nausea, vomiting, and GI issues are common

If you're already taking semaglutide for obesity or diabetes and notice reduced interest in cannabis, you're experiencing what the data predicts. But prescribing semaglutide specifically for CUD would be premature.