Investigating the effects of psilocybin on migraine headaches
Official title: Mechanistic Studies of Psilocybin in Headache Disorders
Run by Yale University · NCT06464367 · Data updated 2026-11-12
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
| Phase | Early Phase 1 |
|---|---|
| Study type | Interventional |
| Ages | 21 Years to 70 Years |
| Sex | All |
| Enrollment | 50 (estimated) |
| Sponsor | Yale University Academic / other |
| Locations | 1 site (West Haven, Connecticut) |
| Status | Recruiting |
| Started | May 19, 2025 |
| Main results expected | December 31, 2027 |
| Study ends | December 31, 2027 |
| Registry record updated | July 13, 2026 |
| Trial ID | NCT06464367 on ClinicalTrials.gov |
Is this trial a fit for you?
✓Likely a good fit
Ideal candidates include adults aged 21 to 70 with a diagnosis of migraine or healthy individuals for comparison.
✕Probably 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.
A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.
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.
Why it matters
Potential benefit: If successful, this study could lead to new treatment options for patients suffering from migraines.
How similar studies have gone: Previous studies have shown promising results with psilocybin in reducing headache burden, suggesting potential for success in this approach.
Who can join: the full rules
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 it's running
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VA Connecticut Healthcare System
West Haven, Connecticut, United States Recruiting
Study contacts
- Study coordinator: Erik Zorrilla, PhD
- Email: erik.zorrilla@yale.edu
- Phone: 203-932-5711
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How to take part
- Review the eligibility criteria above with your treating physician.
- Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
- Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.