Intranasal Oxytocin for Alcohol Use Disorder: A Randomized, Double-Blind, Placebo-Controlled Multisite Trial Assessing Efficacy and Safety

Abstract

Background

The neuropeptide oxytocin offers a potentially effective treatment for alcohol use disorder (AUD). Acting centrally in the brain, oxytocin mediates a range of behavioral effects, including reward, stress response, social affiliation, learning, memory, and addictive behaviors. Animal studies demonstrate oxytocin's ability to reduce alcohol consumption, but results in human trials have been mixed. Some studies report reductions in withdrawal symptoms, heavy drinking, and craving, whereas others show no effects. The purpose of this 12-week clinical trial was to evaluate the efficacy and safety of intranasal oxytocin in individuals with AUD.

Methods

Oxytocin (up to 70 International Units [IU]/day) or placebo was administered to 100 individuals diagnosed with AUD in a double-blind, randomized, 12-week multisite trial. The primary outcome was the weekly percentage of heavy drinking days (PHDD) over 10 weeks of maintenance treatment. Secondary outcomes included additional drinking measures, urge to drink, psychological assessments, alcohol-related consequences, nicotine use, and safety and tolerability of intranasal oxytocin.

Results

No significant differences were observed in PHDD between groups during the 10-week maintenance phase. However, a small, numerically greater reduction in drinking was seen in the oxytocin group compared with placebo from weeks 9 to 12. Similar 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. At the end of treatment, participants receiving oxytocin scored significantly lower on measures of anger and physical aggression. Oxytocin was well tolerated; adverse events were mild and comparable across groups. The most common event in both groups was hyposmia.

Conclusion

Intranasal oxytocin was well tolerated but did not significantly reduce drinking or AUD-related outcomes. Higher doses, longer treatment duration, or larger trials may be required to identify responsive subgroups and determine oxytocin's efficacy in AUD.

Trial Registration

ClinicalTrials.gov, Identifier: NCT03878316. Registered March 14, 2019 (https://clinicaltrials.gov/ct2/show/NCT03878316)