Mechanistic Studies of Psilocybin in Headache Disorders

Recruiting now · Early Phase 1 · Has a placebo group

Conditions studied: Migraine

In brief

In previous clinical trial work, the investigators observed lasting reductions in headache burden after limited dosing of psilocybin. This purpose of this study is to examine potential sources for this observed effect. This study will measure brain resting state functional connectivity (fMRI), central synaptic density (SV2A PET), peripheral markers of inflammation, circadian rhythm (actigraphy), and sleep (sleep EEG) in both migraine and healthy control participants before and one week after the administration of psilocybin or an active control agent.

Key facts

Study ID

NCT06464367

Run by

Yale University

People needed

50

Starts

2025-05-19

Expected to finish

2027-12-31

Last updated by the study team

2026-07-13

Who can join

Age: 21 and older, up to 70. Sex: any. Healthy volunteers: accepted.

You may qualify if…

• 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 is running

• VA Connecticut Healthcare System — West Haven, Connecticut, United States (enrolling)

Full record on ClinicalTrials.gov

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