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Study · Randomized controlled trial · 2025

6 results

Effects of intranasal oxytocin on fear extinction learning.

Rashidi M, Simon JJ, Bertsch K, Wegen GV, Ditzen B, Flor H, Grinevich V, Wolf RC, Herpertz SC

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology24 Sept 2024Cited by 8 (Europe PMC)

PMID39313675 (opens in a new tab)PMCIDPMC11735929 (opens in a new tab)DOI10.1038/s41386-024-01996-y (opens in a new tab)PepBankPUB-39313675
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Summary

Once a threat no longer exists, extinction of conditioned fear becomes adaptive in order to reduce allotted resources towards cues that no longer predict the threat. In anxiety and stress disorders, fear extinction learning may be affected. Animal findings suggest that the administration of oxytocin (OT) modulates extinction learning in a timepoint-dependent manner, facilitating extinction when administered prior to fear conditioning, but impairing it when administered prior to extinction learning. The aim of the present study was to examine if these findings translate into human research. Using a randomized, double-blind, placebo-controlled, 2-day fear conditioning and extinction learning design, behavioral (self-reported anxiety), physiological (skin conductance response), neuronal (task-based and resting-state functional magnetic resonance imaging), and hormonal (cortisol) data were collected from 124 naturally cycling (taking no hormonal contraceptives) healthy females. When administered prior to conditioning (Day 1), OT, similar to rodent findings, did not affect fear conditioning, but modulated the intrinsic functional connectivity of the anterior insula immediately after fear conditioning. In contrast to animal findings, OT impaired, not facilitated, extinction learning on the next day and increased anterior insula activity. When administered prior to extinction learning (day 2), OT increased the activity in the bilateral middle temporal gyrus, and similar to animal findings, reduced extinction learning. The current findings suggest that intranasal OT impedes fear extinction learning in humans regardless of the timepoint of administration, providing new insights and directions for future translational research and clinical applications.
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.

  1. 01HumanRandomized controlled trialEfficacy outcome

    In healthy women, intranasal oxytocin given before conditioning did not affect fear conditioning.

    In plain wordsIn healthy women, oxytocin given before fear conditioning did not change fear conditioning compared with placebo.

    Peptide
    Oxytocin
    Outcome
    No significant changeFear conditioning when given before conditioning
    Study

    n: not reported in source

    Comparator
    Placebo
    Outcome group
    Anxiety and mood · Nervous system and cognition
    Studied dose
    Dose not stated · intranasalAs given in this study (human).

    Source sentences

    Summary
    When administered prior to conditioning (Day 1), OT, similar to rodent findings, did not affect fear conditioning, but modulated the intrinsic functional connectivity of the anterior insula immediately after fear conditioning.
    1 context sentence
    Summary · context
    Using a randomized, double-blind, placebo-controlled, 2-day fear conditioning and extinction learning design, behavioral (self-reported anxiety), physiological (skin conductance response), neuronal (task-based and resting-state functional magnetic resonance imaging), and hormonal (cortisol) data were collected from 124 naturally cycling (taking no hormonal contraceptives) healthy females.
  2. 02HumanRandomized controlled trialMechanism

    In healthy women, intranasal oxytocin given before conditioning modulated intrinsic functional connectivity of the anterior insula immediately after fear conditioning.

    In plain wordsIn healthy women, oxytocin given before fear conditioning changed brain connectivity in a region called the anterior insula.

    Peptide
    Oxytocin
    Outcome
    Direction not reportedAnterior insula intrinsic functional connectivity after fear conditioning
    Study

    n: not reported in source

    Comparator
    Placebo
    Outcome group
    Anxiety and mood · Nervous system and cognition
    Studied dose
    Dose not stated · intranasalAs given in this study (human).

    Source sentences

    Summary
    When administered prior to conditioning (Day 1), OT, similar to rodent findings, did not affect fear conditioning, but modulated the intrinsic functional connectivity of the anterior insula immediately after fear conditioning.
    1 context sentence
    Summary · context
    Using a randomized, double-blind, placebo-controlled, 2-day fear conditioning and extinction learning design, behavioral (self-reported anxiety), physiological (skin conductance response), neuronal (task-based and resting-state functional magnetic resonance imaging), and hormonal (cortisol) data were collected from 124 naturally cycling (taking no hormonal contraceptives) healthy females.
  3. 03HumanRandomized controlled trialEfficacy outcome

    In healthy women, intranasal oxytocin given before conditioning impaired extinction learning on the next day.

    In plain wordsIn healthy women, oxytocin given before fear conditioning made fear extinction learning worse the next day compared with placebo.

    Peptide
    Oxytocin
    Outcome
    DecreaseExtinction learning on day 2 after oxytocin before conditioning
    Study

    n: not reported in source

    Comparator
    Placebo
    Outcome group
    Anxiety and mood · Nervous system and cognition
    Studied dose
    Dose not stated · intranasalAs given in this study (human).

    Source sentences

    Summary
    In contrast to animal findings, OT impaired, not facilitated, extinction learning on the next day and increased anterior insula activity.
    1 context sentence
    Summary · context
    Using a randomized, double-blind, placebo-controlled, 2-day fear conditioning and extinction learning design, behavioral (self-reported anxiety), physiological (skin conductance response), neuronal (task-based and resting-state functional magnetic resonance imaging), and hormonal (cortisol) data were collected from 124 naturally cycling (taking no hormonal contraceptives) healthy females.
  4. 04HumanRandomized controlled trialMechanism

    In healthy women, intranasal oxytocin given before conditioning increased anterior insula activity.

    In plain wordsIn healthy women, oxytocin given before fear conditioning raised activity in the anterior insula compared with placebo.

    Peptide
    Oxytocin
    Outcome
    IncreaseAnterior insula activity during extinction
    Study

    n: not reported in source

    Comparator
    Placebo
    Outcome group
    Brain and neuronal activity · Nervous system and cognition
    Studied dose
    Dose not stated · intranasalAs given in this study (human).

    Source sentences

    Summary
    In contrast to animal findings, OT impaired, not facilitated, extinction learning on the next day and increased anterior insula activity.
    1 context sentence
    Summary · context
    Using a randomized, double-blind, placebo-controlled, 2-day fear conditioning and extinction learning design, behavioral (self-reported anxiety), physiological (skin conductance response), neuronal (task-based and resting-state functional magnetic resonance imaging), and hormonal (cortisol) data were collected from 124 naturally cycling (taking no hormonal contraceptives) healthy females.
  5. 05HumanRandomized controlled trialMechanism

    In healthy women, intranasal oxytocin given before extinction learning increased activity in the bilateral middle temporal gyrus.

    In plain wordsIn healthy women, oxytocin given before extinction learning raised activity in a temporal brain region compared with placebo.

    Peptide
    Oxytocin
    Outcome
    IncreaseBilateral middle temporal gyrus activity
    Study

    n: not reported in source

    Comparator
    Placebo
    Outcome group
    Brain and neuronal activity · Nervous system and cognition
    Studied dose
    Dose not stated · intranasalAs given in this study (human).

    Source sentences

    Summary
    When administered prior to extinction learning (day 2), OT increased the activity in the bilateral middle temporal gyrus, and similar to animal findings, reduced extinction learning.
    1 context sentence
    Summary · context
    Using a randomized, double-blind, placebo-controlled, 2-day fear conditioning and extinction learning design, behavioral (self-reported anxiety), physiological (skin conductance response), neuronal (task-based and resting-state functional magnetic resonance imaging), and hormonal (cortisol) data were collected from 124 naturally cycling (taking no hormonal contraceptives) healthy females.
  6. 06HumanRandomized controlled trialEfficacy outcome

    In healthy women, intranasal oxytocin given before extinction learning reduced extinction learning.

    In plain wordsIn healthy women, oxytocin given before extinction learning reduced fear extinction learning compared with placebo.

    Peptide
    Oxytocin
    Outcome
    DecreaseExtinction learning when given before extinction
    Study

    n: not reported in source

    Comparator
    Placebo
    Outcome group
    Anxiety and mood · Nervous system and cognition
    Studied dose
    Dose not stated · intranasalAs given in this study (human).

    Source sentences

    Summary
    When administered prior to extinction learning (day 2), OT increased the activity in the bilateral middle temporal gyrus, and similar to animal findings, reduced extinction learning.
    1 context sentence
    Summary · context
    Using a randomized, double-blind, placebo-controlled, 2-day fear conditioning and extinction learning design, behavioral (self-reported anxiety), physiological (skin conductance response), neuronal (task-based and resting-state functional magnetic resonance imaging), and hormonal (cortisol) data were collected from 124 naturally cycling (taking no hormonal contraceptives) healthy females.

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, 02:48 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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