Mechanistic Studies of Psilocybin in Headache Disorders

NCT ID: NCT06464367

Last Updated: 2025-07-24

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-05-19
• Study Completion Date: 2026-12-31

Brief 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.

Conditions

Migraine

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: QUADRUPLE

Study Groups

Migraine psilocybin

Migraine participants randomized to receive 10 mg psilocybin (oral)

Group Type: EXPERIMENTAL

Psilocybin

Intervention Type: DRUG

synthetic psilocybin 10 mg (oral)

Migraine placebo

Migraine participants randomized to receive 2.5 mg THC (oral)

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

synthetic THC 2.5 mg (oral)

Healthy control psilocybin

Healthy control participants randomized to receive 10 mg psilocybin (oral)

Group Type: EXPERIMENTAL

Psilocybin

Intervention Type: DRUG

synthetic psilocybin 10 mg (oral)

Healthy control placebo

Healthy control participants randomized to receive 2.5 mg THC

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

synthetic THC 2.5 mg (oral)

Interventions

Psilocybin

synthetic psilocybin 10 mg (oral)

Intervention Type: DRUG

Placebo

synthetic THC 2.5 mg (oral)

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

The Wallace Foundation

OTHER

Sponsor Role: collaborator

Yale University

OTHER

Sponsor Role: lead

Responsible Party

Emmanuelle Schindler

Assistant Professor of Neurology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

VA Connecticut Healthcare System

West Haven, Connecticut, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Sarah Anthony, MSc

Role: CONTACT

sarah.anthony@yale.edu

203-932-5711 ext. 14335

Emmanuelle Schindler, MD, PhD

Role: CONTACT

emmanuelle.schindler@yale.edu

203-932-5711 ext. 14335

Facility Contacts

Sarah Anthony, MSc

Role: primary

sarah.anthony@yale.edu

203-932-5711 ext. 14335

Emmanuelle Schindler, MD, PhD

Role: backup

emmanuelle.schindler@yale.edu

203-932-5711 ext. 14335

Other Identifiers

ES0006

Identifier Type: OTHER

Identifier Source: secondary_id

2000034634

Identifier Type: -

Identifier Source: org_study_id