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Study · Randomized controlled trial · n = 67 · 2025

7 results

Oxytocin Reduces Subjective Fear in Naturalistic Social Contexts via Enhancing Top-Down Middle Cingulate Amygdala Regulation and Brain-Wide Fear Representations.

Fu K, Xu S, Zhang Z, Liu D, Xu T, Zhang Y, Zhou F, Zhang X, Lan C, Wang J, Wang L, He J and 6 more

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Kendrick KM, Biswal B, Yao D, Liang Z, Zhao W, Becker B

Advanced science (Weinheim, Baden-Wurttemberg, Germany)18 Jul 2025Cited by 7 (Europe PMC)

PMID40679087 (opens in a new tab)PMCIDPMC12520527 (opens in a new tab)DOI10.1002/advs.202503251 (opens in a new tab)PepBankPUB-40679087
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Summary

Accumulating evidence from animal and human studies suggests a fear-regulating potential of the neuropeptide oxytocin (OT), yet the clinical translation into novel interventions for pathological fear requires a behavioral and neurofunctional characterization under close-to-real-life conditions. Here, we combined a naturalistic fMRI-design that elicited strong and immersive fear experience in social and non-social contexts with a preregistered between-subjects randomized double-blind placebo-controlled intranasal OT trial (24 IU, n  =  67 healthy men). OT selectively reduced subjective fear in social contexts but not in non-social contexts. On the neural level OT enhanced left middle cingulate cortex (lMCC) activation and its functional connectivity with the contralateral amygdala, with both neural indices significantly and inversely associated with subjective fear following OT. On the network level, OT enhanced communication between the dorsal attention network (DAN) with the fronto-parietal (FPN) and the default-mode network (DMN), and modulated brain-wide communication patterns. Utilizing an independent activity-connectivity neuromarker for fear in naturalistic contexts (CAFE) confirmed that OT attenuated brain-wide fear expressions. Findings indicate an ecologically valid and socially specific fear-reducing effect of OT, highlighting its promise as a treatment option for disorders characterized by excessive fear in social situations.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study7

7 results from studies that gave the peptide. 7 results from people.

  1. 01HumanRandomized controlled trialEfficacy outcome

    In healthy men, intranasal oxytocin reduced subjective fear in social contexts versus placebo.

    In plain wordsIn healthy men, nasal oxytocin reduced felt fear in social settings more than placebo.

    Peptide
    Oxytocin
    Outcome
    DecreaseSubjective fear in social contexts
    Study

    n = 67

    Comparator
    Placebo
    Outcome group
    Anxiety and mood · Mental health and mood
    Studied dose
    24 IU · intranasalAs given in this study (human).

    Source sentences

    Summary
    OT selectively reduced subjective fear in social contexts but not
    1 context sentence
    Summary · context
    Here, we combined a naturalistic fMRI-design that elicited strong and immersive fear experience in social and non-social contexts with a preregistered between-subjects randomized double-blind placebo-controlled intranasal OT trial (24 IU, n  =  67 healthy men).
  2. 02HumanRandomized controlled trialEfficacy outcome

    In healthy men, intranasal oxytocin did not reduce subjective fear in non-social contexts.

    In plain wordsIn healthy men, nasal oxytocin did not reduce felt fear in non-social settings compared with placebo.

    Peptide
    Oxytocin
    Outcome
    No significant changeSubjective fear in non-social contexts
    Study

    n = 67

    Comparator
    Placebo
    Outcome group
    Anxiety and mood · Mental health and mood
    Studied dose
    24 IU · intranasalAs given in this study (human).

    Source sentences

    Summary
    OT selectively reduced subjective fear in social contexts but not in non-social contexts.
    1 context sentence
    Summary · context
    Here, we combined a naturalistic fMRI-design that elicited strong and immersive fear experience in social and non-social contexts with a preregistered between-subjects randomized double-blind placebo-controlled intranasal OT trial (24 IU, n  =  67 healthy men).
  3. 03HumanRandomized controlled trialMechanism

    In healthy men, intranasal oxytocin enhanced left middle cingulate cortex activation during naturalistic fear.

    In plain wordsIn healthy men, nasal oxytocin increased activity in a brain area involved in fear control, compared with placebo.

    Peptide
    Oxytocin
    Outcome
    IncreaseLeft middle cingulate cortex activation
    Study

    n = 67

    Comparator
    Placebo
    Outcome group
    Receptor activity and mechanism · Nervous system and cognition
    Studied dose
    24 IU · intranasalAs given in this study (human).

    Source sentences

    Summary
    On the neural level OT enhanced left middle cingulate cortex (lMCC) activation and its functional connectivity with the contralateral amygdala, with both neural indices significantly and inversely associated with subjective fear following OT.
    1 context sentence
    Summary · context
    Here, we combined a naturalistic fMRI-design that elicited strong and immersive fear experience in social and non-social contexts with a preregistered between-subjects randomized double-blind placebo-controlled intranasal OT trial (24 IU, n  =  67 healthy men).
  4. 04HumanRandomized controlled trialMechanism

    In healthy men, intranasal oxytocin enhanced functional connectivity between the left middle cingulate cortex and the contralateral amygdala.

    In plain wordsIn healthy men, nasal oxytocin strengthened the link between two brain areas involved in fear, compared with placebo.

    Peptide
    Oxytocin
    Outcome
    IncreaseLeft middle cingulate cortex to amygdala functional connectivity
    Study

    n = 67

    Comparator
    Placebo
    Outcome group
    Receptor activity and mechanism · Nervous system and cognition
    Studied dose
    24 IU · intranasalAs given in this study (human).

    Source sentences

    Summary
    On the neural level OT enhanced left middle cingulate cortex (lMCC) activation and its functional connectivity with the contralateral amygdala, with both neural indices significantly and inversely associated with subjective fear following OT.
    1 context sentence
    Summary · context
    Here, we combined a naturalistic fMRI-design that elicited strong and immersive fear experience in social and non-social contexts with a preregistered between-subjects randomized double-blind placebo-controlled intranasal OT trial (24 IU, n  =  67 healthy men).
  5. 05HumanRandomized controlled trialMechanism

    After oxytocin, left middle cingulate activation and its amygdala connectivity were each inversely associated with subjective fear.

    In plain wordsAfter oxytocin, stronger activity and connectivity in these brain areas went with lower felt fear.

    Peptide
    Oxytocin
    Outcome
    Not applicableAssociation of neural indices with subjective fear after oxytocin
    Study

    n = 67

    Outcome group
    Receptor activity and mechanism · Nervous system and cognition
    Studied dose
    24 IU · intranasalAs given in this study (human).

    Source sentences

    Summary
    On the neural level OT enhanced left middle cingulate cortex (lMCC) activation and its functional connectivity with the contralateral amygdala, with both neural indices significantly and inversely associated with subjective fear following OT.
    1 context sentence
    Summary · context
    Here, we combined a naturalistic fMRI-design that elicited strong and immersive fear experience in social and non-social contexts with a preregistered between-subjects randomized double-blind placebo-controlled intranasal OT trial (24 IU, n  =  67 healthy men).
  6. 06HumanRandomized controlled trialMechanism

    In healthy men, intranasal oxytocin enhanced communication of the dorsal attention network with the fronto-parietal and default-mode networks.

    In plain wordsIn healthy men, nasal oxytocin increased communication between large brain networks, compared with placebo.

    Peptide
    Oxytocin
    Outcome
    IncreaseCommunication between dorsal attention network and fronto-parietal and default-mode networks
    Study

    n = 67

    Comparator
    Placebo
    Outcome group
    Receptor activity and mechanism · Nervous system and cognition
    Studied dose
    24 IU · intranasalAs given in this study (human).

    Source sentences

    Summary
    On the network level, OT enhanced communication between the dorsal attention network (DAN) with the fronto-parietal (FPN) and the default-mode network (DMN), and modulated brain-wide communication patterns.
    1 context sentence
    Summary · context
    Here, we combined a naturalistic fMRI-design that elicited strong and immersive fear experience in social and non-social contexts with a preregistered between-subjects randomized double-blind placebo-controlled intranasal OT trial (24 IU, n  =  67 healthy men).
  7. 07HumanRandomized controlled trialMechanism

    In healthy men, intranasal oxytocin attenuated brain-wide fear expressions on an independent neuromarker.

    In plain wordsIn healthy men, nasal oxytocin lowered a brain-wide fear signature, compared with placebo.

    Peptide
    Oxytocin
    Outcome
    DecreaseBrain-wide fear expression (CAFE neuromarker)
    Study

    n = 67

    Comparator
    Placebo
    Outcome group
    Receptor activity and mechanism · Nervous system and cognition
    Studied dose
    24 IU · intranasalAs given in this study (human).

    Source sentences

    Summary
    Utilizing an independent activity-connectivity neuromarker for fear in naturalistic contexts (CAFE) confirmed that OT attenuated brain-wide fear expressions.
    1 context sentence
    Summary · context
    Here, we combined a naturalistic fMRI-design that elicited strong and immersive fear experience in social and non-social contexts with a preregistered between-subjects randomized double-blind placebo-controlled intranasal OT trial (24 IU, n  =  67 healthy men).

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.

  1. Version 2Current

    11 Oct 2026, 00:50 UTC

    Study results updated

  2. Version 1

    9 Oct 2026, 02:47 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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