Intranasal oxytocin blunts amygdala response to negative affective stimuli in males and females with alcohol use disorder: a randomized controlled cross-over trial.

Vetter S, Schnabel S, Reichl M, Sirignano L, Grinevich V, Koopmann A, Spanagel R, Kiefer F, Sommer W, Bach P

Psychopharmacology31 Mar 2025Cited by 3 (Europe PMC)

PMID40232386PMCIDPMC12380973DOI10.1007/s00213-025-06779-xPepBankPUB-40232386

Summary

RationaleNegative affect plays a prominent role in the maintenance of alcohol use disorder (AUD) and has been identified as a risk factor for relapse to alcohol. To date, however, treatment options that target negative affective states and consecutive relapse risk in AUD are insufficient. Oxytocin (OXY) might be a promising approach for addressing negative affective states and resulting motivation to use alcohol.ObjectivesWe aimed to investigate the acute effects of 24 I.U. OXY, administered intranasally, compared to matched placebo (PLC) on central processing of negative emotional stimuli in the amygdala in individuals with AUD.MethodsWe conducted a randomized double-blind placebo-controlled crossover study in N = 24 individuals with AUD. Amygdala response to emotional stimuli served as primary outcome and was assessed using a validated functional magnetic resonance imaging emotion-processing task. Alcohol craving served as secondary outcome.ResultsOXY versus PLC attenuated right amygdala reactivity to fearful and angry emotional face stimuli during the fMRI task (t(33) = 3.32, p_FWE=0.035), while no effect of OXY on amygdala activation was observed during the presentation of geometric figures. In addition, right amygdala reactivity to fearful and angry emotional face stimuli was positively associated with alcohol craving (r =.332, Bias corrected and accelerated 95% confidence interval [95% BCa CI]=-0.044 to 0.624, p =.042).ConclusionsOXY's effects on the neurocircuitry underlying negative affect and craving in AUD support its potential for dampening alcohol craving induced by negative affective states and implicate OXY as a potential future treatment option for AUD.Clinicaltrials registryDRKS00026218.

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

Results from this study3

2 results from studies that gave the peptide. 2 results from people.

01HumanRandomized controlled trialEfficacy outcome
In adults with alcohol use disorder, intranasal oxytocin attenuated right amygdala reactivity to fearful and angry faces compared with placebo.
In plain wordsIn adults with alcohol use disorder, nasal oxytocin lowered the right amygdala response to fearful and angry faces compared with placebo.
Peptide
Oxytocin
Outcome
DecreaseRight amygdala reactivity to fearful and angry faces
Study
n = 24
Comparator
Placebo
Analysis
Primary
Outcome group
Brain and neuronal activity · Mental health and mood
Studied dose
24 IU · intranasalAs given in this study (human).
Source sentences
Summary
OXY versus PLC attenuated right amygdala reactivity to fearful and angry emotional face stimuli during the fMRI task (t(33) = 3.32, p_FWE=0.035)
1 context sentence(design, population, supporting numbers)
Summary · context
We conducted a randomized double-blind placebo-controlled crossover study in N = 24 individuals with AUD.
Show in the study text Report a problemFND-4023238601
02HumanRandomized controlled trialEfficacy outcome
In adults with alcohol use disorder, intranasal oxytocin had no effect on amygdala activation during the presentation of geometric figures.
In plain wordsIn adults with alcohol use disorder, nasal oxytocin did not change the amygdala response to neutral shapes.
Peptide
Oxytocin
Outcome
No significant changeAmygdala activation to geometric figures
Study
n = 24
Comparator
Placebo
Analysis
Primary
Outcome group
Brain and neuronal activity · Mental health and mood
Studied dose
24 IU · intranasalAs given in this study (human).
Source sentences
Summary
while no effect of OXY on amygdala activation was observed during the presentation of geometric figures.
1 context sentence(design, population, supporting numbers)
Summary · context
We conducted a randomized double-blind placebo-controlled crossover study in N = 24 individuals with AUD.
Show in the study text Report a problemFND-4023238602

Studies that did not test the peptide alone1

In this study, Oxytocin was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Oxytocin.

03HumanNot a test of Oxytocin aloneRandomized controlled trialMechanism
In adults with alcohol use disorder, right amygdala reactivity to fearful and angry faces was positively associated with alcohol craving.
In plain wordsIn adults with alcohol use disorder, a stronger amygdala response to fearful and angry faces was linked to more alcohol craving.
Peptide
Oxytocin
Outcome
Not applicableAssociation of amygdala reactivity with alcohol craving
Study
n = 24
Comparator
Placebo
Outcome group
Brain and neuronal activity · Mental health and mood
Source sentences
Summary
In addition, right amygdala reactivity to fearful and angry emotional face stimuli was positively associated with alcohol craving (r =.332, Bias corrected and accelerated 95% confidence interval [95% BCa CI]=-0.044 to 0.624, p =.042).
1 context sentence(design, population, supporting numbers)
Summary · context
We conducted a randomized double-blind placebo-controlled crossover study in N = 24 individuals with AUD.
In this study, Oxytocin was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Oxytocin.
Show in the study text Report a problemFND-4023238603

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

Subjects

Terms as the source lists them.

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