Investigating the effects of psilocybin on migraine headaches

Mechanistic Studies of Psilocybin in Headache Disorders

Early Phase 1 Interventional Yale University · NCT06464367

This study is testing if psilocybin can help reduce migraine headaches by looking at how it affects brain activity and other factors in people with migraines and healthy individuals.

Quick facts

PhaseEarly Phase 1
Study typeInterventional
Enrollment50 (estimated)
Ages21 Years to 70 Years
SexAll
SponsorYale University Academic / other
Locations1 site (West Haven, Connecticut)
Trial IDNCT06464367 on ClinicalTrials.gov

What this trial studies

This study aims to explore the mechanisms behind the observed reductions in headache burden following psilocybin administration. It will involve measuring brain activity through fMRI, assessing synaptic density using SV2A PET imaging, and evaluating peripheral inflammation markers, circadian rhythms, and sleep patterns in both migraine patients and healthy controls. Participants will receive either psilocybin or a placebo, with assessments conducted before and one week after treatment. The goal is to better understand how psilocybin may influence headache disorders.

Who should consider this trial

Good fit: Ideal candidates include adults aged 21 to 70 with a diagnosis of migraine or healthy individuals for comparison.

Not a fit: Patients with unstable medical conditions, serious nervous system pathologies, or those with a history of substance abuse may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to new treatment options for patients suffering from migraines.

How similar studies have performed: Previous studies have shown promising results with psilocybin in reducing headache burden, suggesting potential for success in this approach.

Eligibility criteria

Show full inclusion / exclusion criteria
Inclusion criteria:

* Age 21 to 70 (inclusive)
* Migraine disease per ICHD-3 criteria (for migraine participants) OR Healthy control patient

Exclusion criterion

* Unstable medical condition or serious nervous system pathology
* Pregnant, breastfeeding, lack of adequate birth control
* Psychotic or manic disorder
* Substance abuse in the prior 3 months
* Use of classic psychedelics (e.g., psilocybin, LSD, mescaline) in the past 6 months
* Use of cannabis or other THC products in the prior 2 weeks
* Urine toxicology positive to drugs of abuse
* The use of triptans (e.g., sumatriptan) or ditans (e.g., lasmiditan) more than twice weekly on average
* Use of serotonergic preventive therapies (i.e., taken chronically; amitriptyline, fluoxetine, imipramine, cyproheptadine) in the past 6 weeks
* Use of preventive or transitional treatments that produce spikes and waning of symptom relief (e.g., botulinum toxin, calcitonin gene-related peptide system targeting antibodies, peripheral nerve or ganglion blocks, chiropractic manipulation)
* History of a bleeding disorder or are currently taking anticoagulants (e.g., warfarin, enoxaparin, dabigatran, apixaban).
* Use of non-steroidal anti-inflammatory drugs (NSAIDs; e.g., ibuprofen, naproxen) in the 7 days before PET scan and 7 days after PET scan.

Where this trial is running

West Haven, Connecticut

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Migrainepsilocybinresting state functional connectivitysynaptic densitysynaptic vessel glycoprotein 2Acircadian rhythmsleepinflammation
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.