Does intranasal oxytocin reduce symptoms of mental disorders? A meta-analysis of clinical trials.

Bonnieux J, Gumuchian ST, Harboun A, Trespalacios F, Bélisle KA, Haddad A, Quintus-Bosz O, McLellan A, Chester-Trudel L, Garred D, Resendes T, Hazel L, Wong SF, Ellenbogen MA

Neuroscience and biobehavioral reviews13 May 2026

PMID42134427DOI10.1016/j.neubiorev.2026.106749PepBankPUB-42134427

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Summary

Intranasal administration of oxytocin has been shown to enhance social cognition and reduce stress reactivity in healthy individuals, suggesting therapeutic potential for mental disorders. However, clinical trials have produced mixed results. Following a systematic search, data were extracted from 42 double-blind, randomized controlled trials comparing symptoms following intranasal oxytocin versus placebo in autism spectrum disorder, schizophrenia spectrum disorders, substance use disorders, and other mental disorders. Random effects meta-analysis of the pooled sample (N = 1922) revealed a small, non-significant overall treatment effect with substantial between-trial heterogeneity (g = 0.17, 95% CI [-0.05, 0.38], I² = 77.4%). Removing two outlier studies with very large treatment effects in substance use disorders reduced the pooled estimate and eliminated heterogeneity (g = 0.05, 95% CI [-0.03, 0.12], I² = 0.0%). Analyzing mental disorder subgroups separately revealed a small, significant effect in schizophrenia spectrum disorders (g = 0.12, 95% CI [0.01, 0.23]). Removing outliers uncovered moderation by biological sex, whereby studies with more females showed greater effects (b = 0.0043, p = .02). No significant moderation by dose, number of administrations, psychosocial interventions, or participant age was detected. Findings demonstrate a promising signal in schizophrenia spectrum disorders and potentially important sex differences. However, trial methods seldom aligned with optimal protocols. Future trials should systematically examine dose-response relations, optimize psychosocial interventions, address female underrepresentation, and report individual participant data to enable future meta-analyses to investigate individual differences in treatment response.

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

Results from this study5

5 results from studies that gave the peptide. 5 results from people.

01HumanSystematic reviewEfficacy outcome
In a meta-analysis of 42 randomised trials in mental disorders, intranasal oxytocin had a small, non-significant overall effect on symptoms versus placebo, with substantial heterogeneity.
In plain wordsAcross many mental disorders, oxytocin nose spray did not clearly reduce symptoms more than placebo, and the trials differed a lot.
Peptide
Oxytocin
Outcome
No significant changeOverall symptom change across mental disorders
Study
n = 1,922
Comparator
Placebo
Outcome group
Psychiatric symptoms · Mental health and mood
Studied dose
Dose not stated · intranasalAs given in this study (human).
Measurements
Hedges' g
0.17 g
all trials pooled
I2
77.4%
all trials pooled
Source sentences
Summary
Random effects meta-analysis of the pooled sample (N = 1922) revealed a small, non-significant overall treatment effect with substantial between-trial heterogeneity (g = 0.17, 95% CI [-0.05, 0.38], I² = 77.4%).
1 context sentence(design, population, supporting numbers)
Summary · context
Following a systematic search, data were extracted from 42 double-blind, randomized controlled trials comparing symptoms following intranasal oxytocin versus placebo in autism spectrum disorder, schizophrenia spectrum disorders, substance use disorders, and other mental disorders.
Show in the study text Report a problemFND-4213442701
02HumanSystematic reviewEfficacy outcome
After removing two outlier substance use disorder studies, the pooled effect of intranasal oxytocin versus placebo on symptoms was small and not significant, and heterogeneity disappeared.
In plain wordsWithout two outlier studies, oxytocin nose spray still did not clearly reduce symptoms more than placebo.
Peptide
Oxytocin
Outcome
No significant changeOverall symptom change after removing two outlier studies
Study
n: not reported in source
Comparator
Placebo
Outcome group
Psychiatric symptoms · Mental health and mood
Studied dose
Dose not stated · intranasalAs given in this study (human).
Measurements
Hedges' g
0.05 g
outliers removed
Source sentences
Summary
Removing two outlier studies with very large treatment effects in substance use disorders reduced the pooled estimate and eliminated heterogeneity (g = 0.05, 95% CI [-0.03, 0.12], I² = 0.0%).
1 context sentence(design, population, supporting numbers)
Summary · context
Following a systematic search, data were extracted from 42 double-blind, randomized controlled trials comparing symptoms following intranasal oxytocin versus placebo in autism spectrum disorder, schizophrenia spectrum disorders, substance use disorders, and other mental disorders.
Show in the study text Report a problemFND-4213442702
03HumanSystematic reviewEfficacy outcome
In schizophrenia spectrum disorders, intranasal oxytocin had a small, significant effect on symptoms versus placebo.
In plain wordsIn people with schizophrenia spectrum disorders, oxytocin nose spray had a small effect on symptoms compared with placebo.
Peptide
Oxytocin
Outcome
Direction not reportedSymptom change in schizophrenia spectrum disorders
Study
n: not reported in source
Comparator
Placebo
Outcome group
Psychiatric symptoms · Mental health and mood
Studied dose
Dose not stated · intranasalAs given in this study (human).
Measurements
Hedges' g
0.12 g
schizophrenia spectrum disorders
Source sentences
Summary
Analyzing mental disorder subgroups separately revealed a small, significant effect in schizophrenia spectrum disorders (g = 0.12, 95% CI [0.01, 0.23]).
1 context sentence(design, population, supporting numbers)
Summary · context
Following a systematic search, data were extracted from 42 double-blind, randomized controlled trials comparing symptoms following intranasal oxytocin versus placebo in autism spectrum disorder, schizophrenia spectrum disorders, substance use disorders, and other mental disorders.
Show in the study text Report a problemFND-4213442703
04HumanSystematic reviewOther
After outlier removal, trials of intranasal oxytocin with more female participants showed larger treatment effects.
In plain wordsTrials of oxytocin nose spray with more women showed bigger effects than trials with fewer women.
Peptide
Oxytocin
Outcome
IncreaseModeration of effect by proportion of female participants
Study
n: not reported in source
Comparator
Placebo
Outcome group
Psychiatric symptoms · Mental health and mood
Studied dose
Dose not stated · intranasalAs given in this study (human).
Measurements
Moderation coefficient b
0.0043
proportion of females
Source sentences
Summary
Removing outliers uncovered moderation by biological sex, whereby studies with more females showed greater effects (b = 0.0043, p = .02).
1 context sentence(design, population, supporting numbers)
Summary · context
Following a systematic search, data were extracted from 42 double-blind, randomized controlled trials comparing symptoms following intranasal oxytocin versus placebo in autism spectrum disorder, schizophrenia spectrum disorders, substance use disorders, and other mental disorders.
Show in the study text Report a problemFND-4213442704
05HumanSystematic reviewOther
Treatment effect of intranasal oxytocin was not significantly moderated by dose, number of administrations, psychosocial interventions or participant age.
In plain wordsThe effect of oxytocin nose spray did not differ significantly by dose, number of doses, added therapy or age.
Peptide
Oxytocin
Outcome
No significant changeModeration of effect by dose, number of administrations, psychosocial interventions and age
Study
n: not reported in source
Comparator
Placebo
Outcome group
Psychiatric symptoms · Mental health and mood
Studied dose
Dose not stated · intranasalAs given in this study (human).
Source sentences
Summary
No significant moderation by dose, number of administrations, psychosocial interventions, or participant age was detected.
1 context sentence(design, population, supporting numbers)
Summary · context
Following a systematic search, data were extracted from 42 double-blind, randomized controlled trials comparing symptoms following intranasal oxytocin versus placebo in autism spectrum disorder, schizophrenia spectrum disorders, substance use disorders, and other mental disorders.
Show in the study text Report a problemFND-4213442705

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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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