Oxytocin receptor antagonism in migraine: a randomized, double-blind, placebo-controlled provocation study.

Fitzek MP, Kleist P, Handtmann C, Overeem LH, Hoehne CL, Lange KS, Angerhöfer C, Salim Y, Ebert AD, Mattern N, Reuter U, Raffaelli B

The journal of headache and pain16 Feb 2026Cited by 1 (Europe PMC)

PMID41699456PMCIDPMC12927216DOI10.1186/s10194-026-02297-zPepBankPUB-41699456

Download PDF PubMedAsk about this study

Jump to 6 results

Summary

Background and objectivesOxytocin has been implicated in migraine pathophysiology through its roles in pain modulation and vascular regulation. Its receptors are present in migraine-related brain regions and cerebral vessels and interact with key migraine mediators such as calcitonin gene-related peptide (CGRP). Declining oxytocin levels coincide with increased migraine frequency, but a causal role in humans remains unclear. This study examined whether acute oxytocin receptor blockade provokes migraine attacks or alters cerebrovascular function.MethodsIn this randomized, double-blind, placebo-controlled, cross-over study, women with episodic migraine (WM), healthy women (HC), and men with episodic migraine (MM) aged 18-45 years received the oxytocin receptor antagonist atosiban (6.75 mg bolus followed by 54 mg over 3 h) or placebo on two separate visits. Women used continuous hormonal contraception to ensure stable hormone levels. The primary endpoint was the incidence of migraine-like attacks in WM within 12 h post-infusion. Secondary endpoints included the incidence and intensity of any headache and vascular responses.ResultsA total of 20 WM (27.1 ± 5.6 years), 20 HC (25.7 ± 6.8 years) and 20 MM (29.3 ± 6.1 years) completed both provocations visits. During the 12-hour observation period, the incidence of migraine-like attacks in WM did not differ between atosiban and placebo (atosiban: 6 (30%) vs. placebo: 4 (20%; p = 0.75)). Headache of any kind were reported in 15 (75%) vs. 11 (55%) (p = 0.34). HC did not experience migraine-like attacks, though nine (45%) participants reported headache of any kind after atosiban vs. six (30%) after placebo (p = 0.25). Among MM, migraine attacks occurred in two (10%) participants after atosiban vs. three (15%) after placebo (p > 0.999). While HC showed significantly increased temporal artery diameter and middle cerebral artery flow velocity during atosiban administration, no significant vascular changes were observed in participants with migraine.DiscussionShort-acting oxytocin receptor antagonism did not trigger migraine attacks, suggesting that acute suppression of oxytocin signaling alone is unlikely to trigger migraine under stable hormonal conditions. Instead, oxytocin may act as a modulatory factor within neurovascular networks. Future studies using longer-lasting or brain-penetrant antagonists are needed to further clarify oxytocin's role in migraine susceptibility.Trial registration informationDRKS - Deutsches Register Klinischer Studien: DRKS00033341. Registered: 08.01.2024. First patient enrolled: 08.07.2024.

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

Results from this study6

No result from this study comes from a test of the peptide.

Studies that did not test the peptide alone6

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.

01HumanNot a test of Oxytocin aloneRandomized controlled trialEfficacy outcome
In women with episodic migraine, the oxytocin receptor antagonist atosiban did not change the incidence of migraine-like attacks compared with placebo.
In plain wordsIn women with migraine, the oxytocin blocker atosiban did not trigger more migraine attacks than placebo.
Peptide
Oxytocin
Outcome
No significant changeMigraine-like attacks within 12 h in women with migraine
Study
n = 20
Comparator
Placebo
Analysis
Primary
Outcome group
Pain · Nervous system and cognition
Measurements
Migraine-like attack incidence
30%
atosiban, women with migraine
Migraine-like attack incidence
20%
placebo, women with migraine
Source sentences
Summary
During the 12-hour observation period, the incidence of migraine-like attacks in WM did not differ between atosiban and placebo (atosiban: 6 (30%) vs. placebo: 4 (20%; p = 0.75)).
1 context sentence(design, population, supporting numbers)
Summary · context
In this randomized, double-blind, placebo-controlled, cross-over study, women with episodic migraine (WM), healthy women (HC), and men with episodic migraine (MM) aged 18-45 years received the oxytocin receptor antagonist atosiban (6.75 mg bolus followed by 54 mg over 3 h) or placebo on two separate visits.
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-4169945601
02HumanNot a test of Oxytocin aloneRandomized controlled trialEfficacy outcome
In women with episodic migraine, atosiban did not change the incidence of headache of any kind compared with placebo.
In plain wordsIn women with migraine, the oxytocin blocker atosiban did not cause more headache of any kind than placebo.
Peptide
Oxytocin
Outcome
No significant changeAny headache in women with migraine
Study
n = 20
Comparator
Placebo
Analysis
Secondary
Outcome group
Pain · Nervous system and cognition
Measurements
Headache incidence
75%
atosiban
Headache incidence
55%
placebo
Source sentences
Summary
Headache of any kind were reported in 15 (75%) vs. 11 (55%) (p = 0.34).
1 context sentence(design, population, supporting numbers)
Summary · context
In this randomized, double-blind, placebo-controlled, cross-over study, women with episodic migraine (WM), healthy women (HC), and men with episodic migraine (MM) aged 18-45 years received the oxytocin receptor antagonist atosiban (6.75 mg bolus followed by 54 mg over 3 h) or placebo on two separate visits.
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-4169945602
03HumanNot a test of Oxytocin aloneRandomized controlled trialEfficacy outcome
In healthy women, atosiban did not cause migraine-like attacks, and headache of any kind did not differ significantly from placebo.
In plain wordsIn healthy women, the oxytocin blocker atosiban caused no migraine-like attacks and no significant extra headache compared with placebo.
Peptide
Oxytocin
Outcome
No significant changeAny headache in healthy women
Study
n = 20
Comparator
Placebo
Analysis
Secondary
Outcome group
Pain · Nervous system and cognition
Source sentences
Summary
HC did not experience migraine-like attacks, though nine (45%) participants reported headache of any kind after atosiban vs. six (30%) after placebo (p = 0.25).
1 context sentence(design, population, supporting numbers)
Summary · context
In this randomized, double-blind, placebo-controlled, cross-over study, women with episodic migraine (WM), healthy women (HC), and men with episodic migraine (MM) aged 18-45 years received the oxytocin receptor antagonist atosiban (6.75 mg bolus followed by 54 mg over 3 h) or placebo on two separate visits.
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-4169945603
04HumanNot a test of Oxytocin aloneRandomized controlled trialEfficacy outcome
In healthy women, atosiban significantly increased temporal artery diameter and middle cerebral artery flow velocity.
In plain wordsIn healthy women, the oxytocin blocker atosiban widened a temporal artery and raised blood flow speed in a brain artery.
Peptide
Oxytocin
Outcome
IncreaseTemporal artery diameter and middle cerebral artery flow velocity in healthy women
Study
n = 20
Comparator
Placebo
Analysis
Secondary
Outcome group
Vascular function · Cardiovascular
Source sentences
Summary
HC showed significantly increased temporal artery diameter and middle cerebral artery flow velocity during atosiban administration
1 context sentence(design, population, supporting numbers)
Summary · context
In this randomized, double-blind, placebo-controlled, cross-over study, women with episodic migraine (WM), healthy women (HC), and men with episodic migraine (MM) aged 18-45 years received the oxytocin receptor antagonist atosiban (6.75 mg bolus followed by 54 mg over 3 h) or placebo on two separate visits.
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-4169945605
05HumanNot a test of Oxytocin aloneRandomized controlled trialEfficacy outcome
In participants with migraine, atosiban caused no significant vascular changes.
In plain wordsIn people with migraine, the oxytocin blocker atosiban caused no significant changes in blood vessels.
Peptide
Oxytocin
Outcome
No significant changeVascular responses in participants with migraine
Study
n: not reported in source
Comparator
Placebo
Analysis
Secondary
Outcome group
Vascular function · Cardiovascular
Source sentences
Summary
no significant vascular changes were observed in participants with migraine.
1 context sentence(design, population, supporting numbers)
Summary · context
In this randomized, double-blind, placebo-controlled, cross-over study, women with episodic migraine (WM), healthy women (HC), and men with episodic migraine (MM) aged 18-45 years received the oxytocin receptor antagonist atosiban (6.75 mg bolus followed by 54 mg over 3 h) or placebo on two separate visits.
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-4169945606
06HumanNot a test of Oxytocin aloneRandomized controlled trialEfficacy outcome
In men with episodic migraine, atosiban did not change the incidence of migraine attacks compared with placebo.
In plain wordsIn men with migraine, the oxytocin blocker atosiban did not trigger more migraine attacks than placebo.
Peptide
Oxytocin
Outcome
No significant changeMigraine attacks in men with migraine
Study
n = 20
Comparator
Placebo
Outcome group
Pain · Nervous system and cognition
Source sentences
Summary
Among MM, migraine attacks occurred in two (10%) participants after atosiban vs. three (15%) after placebo (p > 0.999).
1 context sentence(design, population, supporting numbers)
Summary · context
In this randomized, double-blind, placebo-controlled, cross-over study, women with episodic migraine (WM), healthy women (HC), and men with episodic migraine (MM) aged 18-45 years received the oxytocin receptor antagonist atosiban (6.75 mg bolus followed by 54 mg over 3 h) or placebo on two separate visits.
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-4169945604

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, 02:47 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

PepBank is a research reference. Talk to a doctor before you use any peptide.