In the nose or on the tongue? Contrasting motivational effects of oral and intranasal oxytocin on arousal and reward during social processing.

Kou J, Lan C, Zhang Y, Wang Q, Zhou F, Zhao Z, Montag C, Yao S, Becker B, Kendrick KM

Translational psychiatry4 Feb 2021Cited by 33 (Europe PMC)

PMID33542175PMCIDPMC7862637DOI10.1038/s41398-021-01241-wPepBankPUB-33542175

Summary

Intranasal oxytocin exerts wide-ranging effects on socioemotional behavior and is proposed as a potential therapeutic intervention in psychiatric disorders. However, following intranasal administration, oxytocin could penetrate directly into the brain or influence its activity via increased peripheral concentrations crossing the blood-brain barrier or influencing vagal projections. In the current randomized, placebo-controlled, pharmaco-imaging clinical trial we investigated effects of 24IU oral (lingual) oxytocin spray, restricting it to peripherally mediated blood-borne and vagal effects, on responses to face emotions in 80 male subjects and compared them with 138 subjects treated intranasally with 24IU. Oral, but not intranasal oxytocin administration increased both arousal ratings for faces and associated brain reward responses, the latter being partially mediated by blood concentration changes. Furthermore, while oral oxytocin increased amygdala and arousal responses to face emotions, after intranasal administration they were decreased. Thus, oxytocin can produce markedly contrasting motivational effects in relation to socioemotional cues when it influences brain function via different routes. These findings have important implications for future therapeutic use since administering oxytocin orally may be both easier and have potentially stronger beneficial effects by enhancing responses to emotional cues and increasing their associated reward.

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

Results from this study8

8 results from studies that gave the peptide. 8 results from people.

01HumanRandomized controlled trialEfficacy outcome
In healthy men, intranasal oxytocin did not increase arousal ratings for faces.
In plain wordsIn healthy men, nasal oxytocin did not increase arousal ratings for faces.
Peptide
Oxytocin
Outcome
No significant changeArousal ratings for faces after intranasal oxytocin
Study
n = 138
Comparator
Placebo
Outcome group
Anxiety and mood · Nervous system and cognition
Studied dose
24 IU · intranasalAs given in this study (human).
Source sentences
Summary
Oral, but not intranasal oxytocin administration increased both arousal ratings for faces and associated brain reward responses, the latter being partially mediated by blood concentration changes.
1 context sentence(design, population, supporting numbers)
Summary · context
In the current randomized, placebo-controlled, pharmaco-imaging clinical trial we investigated effects of 24IU oral (lingual) oxytocin spray, restricting it to peripherally mediated blood-borne and vagal effects, on responses to face emotions in 80 male subjects and compared them with 138 subjects treated intranasally with 24IU.
Show in the study text Report a problemFND-3354217503
02HumanRandomized controlled trialMechanism
In healthy men, intranasal oxytocin did not increase brain reward responses to faces.
In plain wordsIn healthy men, nasal oxytocin did not increase brain reward responses to faces.
Peptide
Oxytocin
Outcome
No significant changeBrain reward responses to faces after intranasal oxytocin
Study
n = 138
Comparator
Placebo
Outcome group
Brain and neuronal activity · Nervous system and cognition
Studied dose
24 IU · intranasalAs given in this study (human).
Source sentences
Summary
Oral, but not intranasal oxytocin administration increased both arousal ratings for faces and associated brain reward responses, the latter being partially mediated by blood concentration changes.
1 context sentence(design, population, supporting numbers)
Summary · context
In the current randomized, placebo-controlled, pharmaco-imaging clinical trial we investigated effects of 24IU oral (lingual) oxytocin spray, restricting it to peripherally mediated blood-borne and vagal effects, on responses to face emotions in 80 male subjects and compared them with 138 subjects treated intranasally with 24IU.
Show in the study text Report a problemFND-3354217504
03HumanRandomized controlled trialMechanism
In healthy men, intranasal oxytocin decreased amygdala responses to face emotions.
In plain wordsIn healthy men, nasal oxytocin decreased amygdala responses to emotional faces.
Peptide
Oxytocin
Outcome
DecreaseAmygdala response to face emotions after intranasal oxytocin
Study
n = 138
Comparator
Placebo
Outcome group
Brain and neuronal activity · Nervous system and cognition
Studied dose
24 IU · intranasalAs given in this study (human).
Source sentences
Summary
Furthermore, while oral oxytocin increased amygdala and arousal responses to face emotions, after intranasal administration they were decreased.
1 context sentence(design, population, supporting numbers)
Summary · context
In the current randomized, placebo-controlled, pharmaco-imaging clinical trial we investigated effects of 24IU oral (lingual) oxytocin spray, restricting it to peripherally mediated blood-borne and vagal effects, on responses to face emotions in 80 male subjects and compared them with 138 subjects treated intranasally with 24IU.
Show in the study text Report a problemFND-3354217506
04HumanRandomized controlled trialEfficacy outcome
In healthy men, intranasal oxytocin decreased arousal responses to face emotions.
In plain wordsIn healthy men, nasal oxytocin decreased arousal responses to emotional faces.
Peptide
Oxytocin
Outcome
DecreaseArousal responses to face emotions after intranasal oxytocin
Study
n = 138
Comparator
Placebo
Outcome group
Anxiety and mood · Nervous system and cognition
Studied dose
24 IU · intranasalAs given in this study (human).
Source sentences
Summary
Furthermore, while oral oxytocin increased amygdala and arousal responses to face emotions, after intranasal administration they were decreased.
1 context sentence(design, population, supporting numbers)
Summary · context
In the current randomized, placebo-controlled, pharmaco-imaging clinical trial we investigated effects of 24IU oral (lingual) oxytocin spray, restricting it to peripherally mediated blood-borne and vagal effects, on responses to face emotions in 80 male subjects and compared them with 138 subjects treated intranasally with 24IU.
Show in the study text Report a problemFND-3354217507
05HumanRandomized controlled trialEfficacy outcome
In healthy men, oral oxytocin increased arousal ratings for faces.
In plain wordsIn healthy men, oxytocin sprayed on the tongue increased arousal ratings for faces.
Peptide
Oxytocin
Outcome
IncreaseArousal ratings for faces after oral oxytocin
Study
n = 80
Comparator
Placebo
Outcome group
Anxiety and mood · Nervous system and cognition
Studied dose
24 IU · oral (lingual) sprayAs given in this study (human).
Source sentences
Summary
Oral, but not intranasal oxytocin administration increased both arousal ratings for faces
1 context sentence(design, population, supporting numbers)
Summary · context
In the current randomized, placebo-controlled, pharmaco-imaging clinical trial we investigated effects of 24IU oral (lingual) oxytocin spray, restricting it to peripherally mediated blood-borne and vagal effects, on responses to face emotions in 80 male subjects and compared them with 138 subjects treated intranasally with 24IU.
Show in the study text Report a problemFND-3354217501
06HumanRandomized controlled trialMechanism
In healthy men, oral oxytocin increased brain reward responses to faces, partly mediated by blood concentration changes.
In plain wordsIn healthy men, oxytocin sprayed on the tongue increased brain reward responses to faces.
Peptide
Oxytocin
Outcome
IncreaseBrain reward responses to faces after oral oxytocin
Study
n = 80
Comparator
Placebo
Outcome group
Brain and neuronal activity · Nervous system and cognition
Studied dose
24 IU · oral (lingual) sprayAs given in this study (human).
Source sentences
Summary
Oral, but not intranasal oxytocin administration increased both arousal ratings for faces and associated brain reward responses, the latter being partially mediated by blood concentration changes.
1 context sentence(design, population, supporting numbers)
Summary · context
In the current randomized, placebo-controlled, pharmaco-imaging clinical trial we investigated effects of 24IU oral (lingual) oxytocin spray, restricting it to peripherally mediated blood-borne and vagal effects, on responses to face emotions in 80 male subjects and compared them with 138 subjects treated intranasally with 24IU.
Show in the study text Report a problemFND-3354217502
07HumanRandomized controlled trialMechanism
In healthy men, oral oxytocin increased amygdala responses to face emotions.
In plain wordsIn healthy men, oxytocin sprayed on the tongue increased amygdala responses to emotional faces.
Peptide
Oxytocin
Outcome
IncreaseAmygdala response to face emotions after oral oxytocin
Study
n = 80
Comparator
Placebo
Outcome group
Brain and neuronal activity · Nervous system and cognition
Studied dose
24 IU · oral (lingual) sprayAs given in this study (human).
Source sentences
Summary
Furthermore, while oral oxytocin increased amygdala and arousal responses to face emotions, after intranasal administration they were decreased.
1 context sentence(design, population, supporting numbers)
Summary · context
In the current randomized, placebo-controlled, pharmaco-imaging clinical trial we investigated effects of 24IU oral (lingual) oxytocin spray, restricting it to peripherally mediated blood-borne and vagal effects, on responses to face emotions in 80 male subjects and compared them with 138 subjects treated intranasally with 24IU.
Show in the study text Report a problemFND-3354217505
08HumanRandomized controlled trialEfficacy outcome
In healthy men, oral oxytocin increased arousal responses to face emotions.
In plain wordsIn healthy men, oxytocin sprayed on the tongue increased arousal responses to emotional faces.
Peptide
Oxytocin
Outcome
IncreaseArousal responses to face emotions after oral oxytocin
Study
n = 80
Comparator
Placebo
Outcome group
Anxiety and mood · Nervous system and cognition
Studied dose
24 IU · oral (lingual) sprayAs given in this study (human).
Source sentences
Summary
Furthermore, while oral oxytocin increased amygdala and arousal responses to face emotions, after intranasal administration they were decreased.
1 context sentence(design, population, supporting numbers)
Summary · context
In the current randomized, placebo-controlled, pharmaco-imaging clinical trial we investigated effects of 24IU oral (lingual) oxytocin spray, restricting it to peripherally mediated blood-borne and vagal effects, on responses to face emotions in 80 male subjects and compared them with 138 subjects treated intranasally with 24IU.
Show in the study text Report a problemFND-3354217508

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, 02:48 UTC
First added · source update from Europe PMC

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