RecruitingEarly Phase 1NCT06464367

Mechanistic Studies of Psilocybin in Headache Disorders


Sponsor

Yale University

Enrollment

50 participants

Start Date

May 19, 2025

Study Type

INTERVENTIONAL

Conditions

Summary

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.


Eligibility

Min Age: 21 YearsMax Age: 70 Years

Inclusion Criteria15

  • 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.

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Interventions

DRUGPsilocybin

synthetic psilocybin 10 mg (oral)

DRUGPlacebo

synthetic THC 2.5 mg (oral)


Locations(1)

VA Connecticut Healthcare System

West Haven, Connecticut, United States

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NCT06464367


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