Intranasal Oxytocin Fails to Significantly Reduce Drinking or AUD Symptoms in 100-Patient Trial

Alcohol Use Disorder (AUD) remains a significant public health challenge, with current treatments often having limited efficacy or side effects. The neuropeptide oxytocin has emerged as a potential therapeutic agent due to its central role in mediating reward, stress response, and addictive behaviors. Animal studies have shown oxytocin's ability to reduce alcohol consumption, yet human trials have yielded mixed results, with some reporting benefits and others showing no effect. This 12-week clinical trial aimed to clarify the efficacy and safety of intranasal oxytocin for individuals with AUD.

This double-blind, randomized, placebo-controlled multisite trial enrolled 100 individuals diagnosed with AUD. Participants received either intranasal oxytocin (titrated up to 70 International Units [IU]/day) or placebo for 12 weeks. The primary outcome measured was the weekly percentage of heavy drinking days (PHDD) over a 10-week maintenance treatment phase. Secondary outcomes included various other drinking measures, self-reported urge to drink, psychological assessments, alcohol-related consequences, nicotine use, and a comprehensive evaluation of safety and tolerability.

No significant differences were observed in the primary outcome of PHDD between the oxytocin and placebo groups during the 10-week maintenance phase. However, a small, numerically greater reduction in drinking was noted in the oxytocin group compared with placebo from weeks 9 to 12. Similar non-significant patterns were found across secondary drinking outcomes. No significant differences were observed in AUD symptoms, alcohol-related consequences, craving, mood, sleep, pain, or substance use. Notably, at the end of treatment, participants receiving oxytocin scored significantly lower on measures of anger and physical aggression. Oxytocin was well tolerated, with adverse events being mild and comparable across both groups. The most common adverse event reported in both groups was hyposmia. The study did not report specific p-values for the primary outcome, indicating a lack of statistical significance.