Mechanistic Studies of Psilocybin in Headache Disorders

Early Phase 1RecruitingNCT06464367

Yale University50 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

OTHER

Masking

QUADRUPLE

Enrollment

Conditions

Migraine

Interventions

PsilocybinDRUG

synthetic psilocybin 10 mg (oral)

PlaceboDRUG

synthetic THC 2.5 mg (oral)

Eligibility

Sex: ALLMin age: 21 YearsMax age: 70 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (1)

VA Connecticut Healthcare System

West Haven, Connecticut, United States

RECRUITING

Outcomes

Primary Outcomes

Baseline SV2A PET

Comparing initial SV2A PET between migraine and HC

Time frame: from date of randomization until the date of first PET scan, assessed up to 6 months

Baseline RSFC

Comparing initial RSFC between migraine and HC

Time frame: from date of randomization until the date of first MRI, assessed up to 6 months

Change in SV2A PET after drug administration

Comparing change in SV2A PET after drug between psilocybin/THC and migraine/HC

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

Comparing change in RSFC after drug between psilocybin/THC and migraine/HC

Time frame: from date of first MRI to the date of second MRI, assessed up to 6 months

Secondary Outcomes

Change in TNF-alpha

Comparing change in TNF-alpha levels after drug between psilocybin/THC and migraine/HC

Time frame: from screening to 7 days after drug administration

Change in IL-1beta

Comparing change in IL-1beta levels after drug between psilocybin/THC and migraine/HC

Time frame: from screening to 7 days after drug administration

Change in IL-6

Comparing change in IL-6 levels after drug between psilocybin/THC and migraine/HC

Time frame: from screening to 7 days after drug administration

Central Contacts

Sarah Anthony, MSc

CONTACT

203-932-5711 sarah.anthony@yale.edu

Emmanuelle Schindler, MD, PhD

CONTACT

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

Data from ClinicalTrials.gov

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