Use of oral semaglutide results in substantial decreases in alcohol consumption, alcohol craving, alcohol-related problems, and cannabis use among individuals seeking treatment from alcohol use disorder (AUD), a study has shown.
“These findings confirm previous results among nontreatment seekers with less severe AUD and suggest that continued development of semaglutide for AUD is warranted,” the investigators said.
Fifty individuals with moderate to severe AUD were randomized to treatment with semaglutide (3 mg/day for 4 weeks, then 7 mg/day for 4 weeks) or placebo for 8 weeks. Laboratory-based alcohol cue-elicited craving at week 6 was the primary outcome, while secondary outcomes included heavy drinking days and drinks per day during the last 4 weeks of treatment.
The investigators also explored the effects of semaglutide on other alcohol consumption measures, naturalistic alcohol craving, alcohol-related negative consequences, World Health Organization risk drinking level, and cannabis use.
Participants in the semaglutide group did not display a substantial reduction in laboratory-assessed craving or drinks per day compared with those in the placebo group. However, heavy drinking days significantly decreased with semaglutide (b, ‒0.580, 95 percent confidence interval [CI], ‒1.012 to ‒0.148). [Am J Psychiatry 2026;183:636-645]
Likewise, the semaglutide group demonstrated significant reductions in drinks per drinking day (b, ‒1.177, 95 percent CI, ‒2.307 to ‒0.047), naturalistic alcohol craving (b, ‒2.195, 95 percent CI, ‒4.174 to ‒0.216), and cannabis use days (b, ‒1.434, 95 percent CI, ‒2.568 to ‒0.301).
Semaglutide was also more effective than placebo in reducing alcohol-related consequences (b, ‒4.618, 95 percent CI, ‒8.651 to ‒0.585). Notably, more participants treated with semaglutide than with placebo lowered their risk drinking level by at least one level (Wald χ2=4.01).
“Although oral semaglutide, relative to placebo, did not significantly reduce laboratory-based alcohol cue-elicited craving as assessed by a single item, its effects on other craving measures, both in the laboratory and in the natural environment, on alcohol consumption and on alcohol-related consequences provide promising evidence of its potential efficacy for AUD,” the investigators said.
“Semaglutide was well-tolerated, with rates of gastrointestinal and other adverse events similar to other populations and low adverse-event-related dropout,” they added.
These findings support those of a previous study involving injectable semaglutide among nontreatment-seeking individuals with AUD in a higher-severity population. [JAMA Psychiatry 2025;82:395-405]
Cannabis use
One interesting finding of the current study is the reduction in alcohol consumption among individuals with high rates of cannabis use, according to the investigators.
While earlier studies suggest that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) reduce cannabis use disorder incidence and relapse, no previous trials have explored cannabis use outcomes. [Mol Psychiatry 2024;29:2587-2598]
“[T]hus, semaglutide’s reduction of cannabis use days in the present trial, though exploratory, is novel and merits follow-up in larger trials,” the investigators said.
“Future studies could examine whether reductions in cannabis use days vary by the typical form of cannabis consumed (eg, ingested vs inhaled) or by medical versus recreational use status, as these factors may influence pharmacokinetics, reward salience, and cue-driven use patterns that are potentially relevant to semaglutide’s effects on appetite and reward processing,” they added.