Oxytocin efficacy is modulated by dosage and oxytocin receptor genotype in young adults with high-functioning autism: a 24-week randomized clinical trial.

Kosaka H, Okamoto Y, Munesue T, Yamasue H, Inohara K, Fujioka T, Anme T, Orisaka M, Ishitobi M, Jung M, Fujisawa TX, Tanaka S and 10 more

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Arai S, Asano M, Saito DN, Sadato N, Tomoda A, Omori M, Sato M, Okazawa H, Higashida H, Wada Y

Translational psychiatry23 Aug 2016Cited by 95 (Europe PMC)

PMID27552585PMCIDPMC5022092DOI10.1038/tp.2016.152PepBankPUB-27552585

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Summary

Recent studies have suggested that long-term oxytocin administration can alleviate the symptoms of autism spectrum disorder (ASD); however, factors influencing its efficacy are still unclear. We conducted a single-center phase 2, pilot, randomized, double-blind, placebo-controlled, parallel-group, clinical trial in young adults with high-functioning ASD, to determine whether oxytocin dosage and genetic background of the oxytocin receptor affects oxytocin efficacy. This trial consisted of double-blind (12 weeks), open-label (12 weeks) and follow-up phases (8 weeks). To examine dose dependency, 60 participants were randomly assigned to high-dose (32 IU per day) or low-dose intranasal oxytocin (16 IU per day), or placebo groups during the double-blind phase. Next, we measured single-nucleotide polymorphisms (SNPs) in the oxytocin receptor gene (OXTR). In the intention-to-treat population, no outcomes were improved after oxytocin administration. However, in male participants, Clinical Global Impression-Improvement (CGI-I) scores in the high-dose group, but not the low-dose group, were significantly higher than in the placebo group. Furthermore, we examined whether oxytocin efficacy, reflected in the CGI-I scores, is influenced by estimated daily dosage and OXTR polymorphisms in male participants. We found that >21 IU per day oxytocin was more effective than ⩽21 IU per day, and that a SNP in OXTR (rs6791619) predicted CGI-I scores for ⩽21 IU per day oxytocin treatment. No severe adverse events occurred. These results suggest that efficacy of long-term oxytocin administration in young men with high-functioning ASD depends on the oxytocin dosage and genetic background of the oxytocin receptor, which contributes to the effectiveness of oxytocin treatment of ASD.

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.

01HumanRandomized controlled trialEfficacy outcome
In young adults with high-functioning autism spectrum disorder, no outcome improved with intranasal oxytocin in the intention-to-treat population.
In plain wordsIn young adults with high-functioning autism, no outcome improved with oxytocin overall in the main analysis.
Peptide
Oxytocin
Outcome
No significant changeAutism symptom outcomes, intention-to-treat population
Study
n = 60
Comparator
Placebo
Outcome group
Autism core symptoms · Mental health and mood
Studied dose
16 or 32 IU per day · intranasal · 12 weeksAs given in this study (human).
Source sentences
Summary
In the intention-to-treat population, no outcomes were improved after oxytocin administration.
2 context sentences(design, population, supporting numbers)
Summary · context
We conducted a single-center phase 2, pilot, randomized, double-blind, placebo-controlled, parallel-group, clinical trial in young adults with high-functioning ASD, to determine whether oxytocin dosage and genetic background of the oxytocin receptor affects oxytocin efficacy.
Summary · context
To examine dose dependency, 60 participants were randomly assigned to high-dose (32 IU per day) or low-dose intranasal oxytocin (16 IU per day), or placebo groups during the double-blind phase.
Show in the study text Report a problemFND-2755258501
02HumanRandomized controlled trialSafety outcome
In young adults with high-functioning autism, no severe adverse events occurred with intranasal oxytocin.
In plain wordsIn young adults with autism, no severe side effects occurred with oxytocin.
Peptide
Oxytocin
Outcome
No significant changeSevere adverse events
Study
n = 60
Outcome group
Adverse events · Whole body
Studied dose
16 or 32 IU per day · intranasalAs given in this study (human).
Source sentences
Summary
No severe adverse events occurred.
2 context sentences(design, population, supporting numbers)
Summary · context
We conducted a single-center phase 2, pilot, randomized, double-blind, placebo-controlled, parallel-group, clinical trial in young adults with high-functioning ASD, to determine whether oxytocin dosage and genetic background of the oxytocin receptor affects oxytocin efficacy.
Summary · context
To examine dose dependency, 60 participants were randomly assigned to high-dose (32 IU per day) or low-dose intranasal oxytocin (16 IU per day), or placebo groups during the double-blind phase.
Show in the study text Report a problemFND-2755258506
03HumanRandomized controlled trialEfficacy outcome
In young men with high-functioning autism, CGI-I scores were significantly higher with high-dose oxytocin than with placebo.
In plain wordsIn young men with autism, high-dose oxytocin gave higher global improvement scores than placebo.
Peptide
Oxytocin
Outcome
IncreaseCGI-I score, high-dose oxytocin versus placebo, male participants
Study
n: not reported in source
Comparator
Placebo
Outcome group
Anxiety and mood · Mental health and mood
Studied dose
32 IU per day · intranasal · 12 weeksAs given in this study (human).
Source sentences
Summary
in male participants, Clinical Global Impression-Improvement (CGI-I) scores in the high-dose group, but not the low-dose group, were significantly higher than in the placebo group.
2 context sentences(design, population, supporting numbers)
Summary · context
We conducted a single-center phase 2, pilot, randomized, double-blind, placebo-controlled, parallel-group, clinical trial in young adults with high-functioning ASD, to determine whether oxytocin dosage and genetic background of the oxytocin receptor affects oxytocin efficacy.
Summary · context
To examine dose dependency, 60 participants were randomly assigned to high-dose (32 IU per day) or low-dose intranasal oxytocin (16 IU per day), or placebo groups during the double-blind phase.
Show in the study text Report a problemFND-2755258502
04HumanRandomized controlled trialEfficacy outcome
In young men with high-functioning autism, CGI-I scores with low-dose oxytocin did not differ significantly from placebo.
In plain wordsIn young men with autism, low-dose oxytocin did not give higher global improvement scores than placebo.
Peptide
Oxytocin
Outcome
No significant changeCGI-I score, low-dose oxytocin versus placebo, male participants
Study
n: not reported in source
Comparator
Placebo
Outcome group
Anxiety and mood · Mental health and mood
Studied dose
16 IU per day · intranasal · 12 weeksAs given in this study (human).
Source sentences
Summary
However, in male participants, Clinical Global Impression-Improvement (CGI-I) scores in the high-dose group, but not the low-dose group, were significantly higher than in the placebo group.
2 context sentences(design, population, supporting numbers)
Summary · context
We conducted a single-center phase 2, pilot, randomized, double-blind, placebo-controlled, parallel-group, clinical trial in young adults with high-functioning ASD, to determine whether oxytocin dosage and genetic background of the oxytocin receptor affects oxytocin efficacy.
Summary · context
To examine dose dependency, 60 participants were randomly assigned to high-dose (32 IU per day) or low-dose intranasal oxytocin (16 IU per day), or placebo groups during the double-blind phase.
Show in the study text Report a problemFND-2755258503
05HumanRandomized controlled trialEfficacy outcome
In young men with high-functioning autism, oxytocin above 21 IU per day was more effective on CGI-I than 21 IU per day or less.
In plain wordsIn young men with autism, oxytocin above 21 IU per day worked better than 21 IU per day or less.
Peptide
Oxytocin
Outcome
IncreaseCGI-I score by estimated daily oxytocin dose, male participants
Study
n: not reported in source
Comparator
Oxytocin 21 IU per day or less
Outcome group
Anxiety and mood · Mental health and mood
Studied dose
more than 21 IU per day · intranasalAs given in this study (human).
Source sentences
Summary
We found that >21 IU per day oxytocin was more effective than ⩽21 IU per day, and that a SNP in OXTR (rs6791619) predicted CGI-I scores for ⩽21 IU per day oxytocin treatment.
1 context sentence(design, population, supporting numbers)
Summary · context
Furthermore, we examined whether oxytocin efficacy, reflected in the CGI-I scores, is influenced by estimated daily dosage and OXTR polymorphisms in male participants.
Show in the study text Report a problemFND-2755258504
06HumanRandomized controlled trialOther
In young men with high-functioning autism given 21 IU per day oxytocin or less, an OXTR SNP (rs6791619) predicted CGI-I scores.
In plain wordsIn young men with autism on lower oxytocin doses, a variant in the oxytocin receptor gene predicted how much they improved.
Peptide
Oxytocin
Outcome
Not applicableOXTR SNP rs6791619 as predictor of CGI-I at 21 IU per day or less
Study
n: not reported in source
Outcome group
Anxiety and mood · Mental health and mood
Studied dose
21 IU per day or less · intranasalAs given in this study (human).
Source sentences
Summary
and that a SNP in OXTR (rs6791619) predicted CGI-I scores for ⩽21 IU per day oxytocin treatment.
2 context sentences(design, population, supporting numbers)
Summary · context
We conducted a single-center phase 2, pilot, randomized, double-blind, placebo-controlled, parallel-group, clinical trial in young adults with high-functioning ASD, to determine whether oxytocin dosage and genetic background of the oxytocin receptor affects oxytocin efficacy.
Summary · context
To examine dose dependency, 60 participants were randomly assigned to high-dose (32 IU per day) or low-dose intranasal oxytocin (16 IU per day), or placebo groups during the double-blind phase.
Show in the study text Report a problemFND-2755258505

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, 01:30 UTC
Study results updated
Version 1
9 Oct 2026, 02:49 UTC
First added · source update from Europe PMC

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