Intranasal oxytocin for alcohol use disorder: A systematic review and multilevel, bayesian, and variance meta-analyses of randomized clinical trial data.

Santos VH, Paloyelis Y, Morgado M, Rodrigues JR, Tjeng R, Fraga M, Carriço P, Fernandes L, Martins D

Psychoneuroendocrinology11 Jun 2026

PMID42335670DOI10.1016/j.psyneuen.2026.107915PepBankPUB-42335670

Publisher page PubMedAsk about this study

Summary

BackgroundIntranasal oxytocin (OT) has been proposed as a promising adjunctive treatment for Alcohol Use Disorder (AUD), yet randomized controlled trials (RCTs) have yielded mixed and inconclusive findings. To clarify its therapeutic potential, we conducted a comprehensive meta-analysis using frequentist, Bayesian, and variability-based approaches.MethodsWe performed a multilevel random-effects meta-analysis of six eligible RCTs comparing intranasal OT with placebo for alcohol-related outcomes. Hedges' g values were calculated and winsorised at |g| = 3 to limit leverage from extreme small-sample effects. Moderator analyses assessed outcome domain, OT dose, treatment duration, year of publication, administration frequency, and clinical setting. Publication bias was evaluated using multilevel PET-PEESE with cluster-robust correction, Egger's test, trim-and-fill, and limit meta-analysis. Bayesian multilevel models examined average treatment effects and outcome variability.ResultsThe overall pooled effect was not statistically significant (Hedges' g = 0.34, 95% CI -0.48-1.17, p = 0.47), with substantial between-study heterogeneity (Q(48) = 504.40, p < .001). Cook's distance identified Pedersen et al. (2013) as statistically influential; moderator and publication bias analyses were conducted on the remaining five studies. No significant moderation was observed by outcome domain, dose, duration, frequency, or setting. Year of publication showed a nominally significant positive association with effect size in the restricted sample (β = 0.184, p = .042). Multiple publication bias diagnostics converged on the absence of a systematic adjusted effect. Bayesian multilevel analysis confirmed the absence of a credible treatment effect (posterior mean μ = -0.005, 95% CrI -0.53-0.52). Robust Bayesian meta-analysis provided moderate support for the null hypothesis (BF₀₁ = 4.74). Variability analyses found no evidence that OT increased outcome dispersion relative to placebo (lnVR = -0.146, p = .153 after robust correction), providing no support for latent responder subgroups.ConclusionsContrary to early expectations, intranasal OT does not confer a consistent therapeutic benefit across alcohol-related outcomes. The lack of evidence for publication bias or increased outcome variability argues against latent differential responsiveness driving effects. Nonetheless, context-sensitive signals - particularly in domains related to social-cognitive processing - underscore the need for mechanistically informed trials. Future research should prioritise precision frameworks to clarify when, for whom, and under what conditions OT may yield meaningful clinical benefit.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study6

6 results from studies that gave the peptide. 6 results from people.

01HumanSystematic reviewEfficacy outcome
In a meta-analysis of six trials in alcohol use disorder, intranasal oxytocin had no statistically significant pooled effect on alcohol-related outcomes versus placebo.
In plain wordsAcross six trials in alcohol use disorder, oxytocin nose spray did not significantly improve alcohol-related outcomes compared with placebo.
Peptide
Oxytocin
Outcome
No significant changeOverall pooled effect on alcohol-related outcomes
Study
n: not reported in source
Comparator
Placebo
Outcome group
Addiction, withdrawal and alcohol intake · Mental health and mood
Studied dose
Dose not stated · intranasalAs given in this study (human).
Measurements
Hedges' g
0.34 g
overall pooled
Source sentences
Summary
The overall pooled effect was not statistically significant (Hedges' g = 0.34, 95% CI -0.48-1.17, p = 0.47), with substantial between-study heterogeneity (Q(48) = 504.40, p < .001).
1 context sentence(design, population, supporting numbers)
Summary · context
We performed a multilevel random-effects meta-analysis of six eligible RCTs comparing intranasal OT with placebo for alcohol-related outcomes.
Show in the study text Report a problemFND-4233567001
02HumanSystematic reviewOther
No significant moderation of the oxytocin effect on alcohol-related outcomes was observed by outcome domain, dose, duration, frequency or setting.
In plain wordsThe effect of oxytocin nose spray on alcohol outcomes did not differ significantly by outcome type, dose, length, frequency or setting.
Peptide
Oxytocin
Outcome
No significant changeModeration by outcome domain, dose, duration, frequency and setting
Study
n: not reported in source
Comparator
Placebo
Outcome group
Addiction, withdrawal and alcohol intake · Mental health and mood
Studied dose
Dose not stated · intranasalAs given in this study (human).
Source sentences
Summary
No significant moderation was observed by outcome domain, dose, duration, frequency, or setting.
1 context sentence(design, population, supporting numbers)
Summary · context
We performed a multilevel random-effects meta-analysis of six eligible RCTs comparing intranasal OT with placebo for alcohol-related outcomes.
Show in the study text Report a problemFND-4233567002
03HumanSystematic reviewOther
In the restricted sample of five trials, later publication year showed a nominally significant positive association with the oxytocin effect size.
In plain wordsNewer trials of oxytocin nose spray in alcohol use disorder tended to show larger effects, but this was only nominally significant.
Peptide
Oxytocin
Outcome
IncreaseAssociation of publication year with effect size
Study
n: not reported in source
Comparator
Placebo
Outcome group
Addiction, withdrawal and alcohol intake · Mental health and mood
Studied dose
Dose not stated · intranasalAs given in this study (human).
Source sentences
Summary
Year of publication showed a nominally significant positive association with effect size in the restricted sample (β = 0.184, p = .042).
1 context sentence(design, population, supporting numbers)
Summary · context
We performed a multilevel random-effects meta-analysis of six eligible RCTs comparing intranasal OT with placebo for alcohol-related outcomes.
Show in the study text Report a problemFND-4233567003
04HumanSystematic reviewEfficacy outcome
Bayesian multilevel analysis found no credible effect of intranasal oxytocin on alcohol-related outcomes versus placebo.
In plain wordsA Bayesian analysis found no sign that oxytocin nose spray improved alcohol-related outcomes compared with placebo.
Peptide
Oxytocin
Outcome
No significant changeBayesian estimate of average treatment effect
Study
n: not reported in source
Comparator
Placebo
Outcome group
Addiction, withdrawal and alcohol intake · Mental health and mood
Studied dose
Dose not stated · intranasalAs given in this study (human).
Measurements
Posterior mean
−0.005 g
Bayesian multilevel model
Source sentences
Summary
Bayesian multilevel analysis confirmed the absence of a credible treatment effect (posterior mean μ = -0.005, 95% CrI -0.53-0.52).
1 context sentence(design, population, supporting numbers)
Summary · context
We performed a multilevel random-effects meta-analysis of six eligible RCTs comparing intranasal OT with placebo for alcohol-related outcomes.
Show in the study text Report a problemFND-4233567004
05HumanSystematic reviewEfficacy outcome
Robust Bayesian meta-analysis gave moderate support for no effect of intranasal oxytocin on alcohol-related outcomes.
In plain wordsA robust Bayesian analysis moderately supported the view that oxytocin nose spray has no effect on alcohol outcomes.
Peptide
Oxytocin
Outcome
No significant changeRobust Bayesian support for null hypothesis
Study
n: not reported in source
Comparator
Placebo
Outcome group
Addiction, withdrawal and alcohol intake · Mental health and mood
Studied dose
Dose not stated · intranasalAs given in this study (human).
Measurements
Bayes factor BF01
4.74
robust Bayesian meta-analysis
Source sentences
Summary
Robust Bayesian meta-analysis provided moderate support for the null hypothesis (BF₀₁ = 4.74).
1 context sentence(design, population, supporting numbers)
Summary · context
We performed a multilevel random-effects meta-analysis of six eligible RCTs comparing intranasal OT with placebo for alcohol-related outcomes.
Show in the study text Report a problemFND-4233567005
06HumanSystematic reviewEfficacy outcome
Intranasal oxytocin did not increase outcome variability relative to placebo, giving no support for latent responder subgroups.
In plain wordsOxytocin nose spray did not make outcomes more variable than placebo, so there was no sign of a hidden group of responders.
Peptide
Oxytocin
Outcome
No significant changeOutcome variability relative to placebo
Study
n: not reported in source
Comparator
Placebo
Outcome group
Addiction, withdrawal and alcohol intake · Mental health and mood
Studied dose
Dose not stated · intranasalAs given in this study (human).
Measurements
lnVR
−0.146
oxytocin versus placebo
Source sentences
Summary
Variability analyses found no evidence that OT increased outcome dispersion relative to placebo (lnVR = -0.146, p = .153 after robust correction), providing no support for latent responder subgroups.
1 context sentence(design, population, supporting numbers)
Summary · context
We performed a multilevel random-effects meta-analysis of six eligible RCTs comparing intranasal OT with placebo for alcohol-related outcomes.
Show in the study text Report a problemFND-4233567006

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
11 Oct 2026, 00:50 UTC
Study results updated
Version 1
9 Oct 2026, 02:47 UTC
First added · source update from Europe PMC

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Terms as the source lists them.

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