Recruiting
Early Phase 1

Psilocybin

Sponsor:

Yale University

Code:

NCT06464367

Conditions

Migraine

Eligibility Criteria

Sex: All

Age: 21 - 70

Healthy Volunteers: Accepted

Interventions

Psilocybin

Placebo

Study Details

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 ID

NCT06464367

Start date

May 19, 2025

Status verified date

Jul, 2026

Completion date

Dec 31, 2027

Anticipated

Primary completion date

Dec 31, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 21 - 70

Healthy Volunteers: Accepted

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.

Study Design

Enrollment

50 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Other

Interventions and Outcome Measures

Arms

experimental: Migraine psilocybin

Migraine participants randomized to receive 10 mg psilocybin (oral)

placebo comparator: Migraine placebo

Migraine participants randomized to receive 2.5 mg THC (oral)

experimental: Healthy control psilocybin

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

placebo comparator: Healthy control placebo

Healthy control participants randomized to receive 2.5 mg THC

Interventions

Psilocybin

synthetic psilocybin 10 mg (oral)

Placebo

synthetic THC 2.5 mg (oral)

Primary outcome measure

  • Baseline SV2A PET [ Time Frame: from date of randomization until the date of first PET scan, assessed up to 6 months ]
  • Baseline RSFC [ Time Frame: from date of randomization until the date of first MRI, assessed up to 6 months ]
  • Change in SV2A PET after drug administration [ Time Frame: from date of first PET scan to the date of second PET scan, assessed up to 6 months ]
  • Change in resting state functional connectivity (RSFC) after drug administration [ Time Frame: from date of first MRI to the date of second MRI, assessed up to 6 months ]

Central Contacts and Locations

Central contacts

Erik Zorrilla, PhD

203-932-5711erik.zorrilla@yale.edu

Emmanuelle Schindler, MD, PhD

203-932-5711emmanuelle.schindler@yale.edu

Locations

VA Connecticut Healthcare System

Recruiting

West Haven, Connecticut, United States, 06516

Contacts

Erik Zorrilla, PhD

203-932-5711erik.zorrilla@yale.edu

Emmanuelle Schindler, MD, PhD

203-932-5711emmanuelle.schindler@yale.edu

More Information

Sponsor

Yale University

Last update posted

Jul 13, 2026

Last verified

Jul, 2026

Keywords

  • psilocybin
  • resting state functional connectivity
  • synaptic density
  • synaptic vessel glycoprotein 2A (SV2A)
  • circadian rhythm
  • sleep
  • inflammation

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-07. This information was provided to ClinicalTrials.gov by Yale University on 2026-07-13. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.