Clinical TrialHeadache Disorders (Cluster & Migraine)PsilocybinPlaceboPsilocybinPlaceboRecruiting

Mechanistic Studies of Psilocybin in Headache Disorders

This interventional trial (n=50) will explore mechanisms of psilocybin in migraine and healthy controls using a randomized, parallel, quadruple-blind design with oral psilocybin 10 mg versus 2.5 mg THC control.

Target Enrollment
50 participants
Study Type
Phase I interventional
Design
Randomized, quadruple Blind

Detailed Description

Randomized, parallel-group study comparing a single oral 10 mg dose of psilocybin with a 2.5 mg THC control in migraine patients and healthy controls to probe mechanisms underlying reduced headache burden observed in prior work.

Outcomes include resting-state fMRI, SV2A PET for synaptic density, peripheral inflammatory markers, actigraphy for circadian rhythms, and sleep EEG measured before and one week after dosing.

Study Protocol

Preparation

sessions

Dosing

1 sessions

Integration

sessions

Study Arms & Interventions

Migraine psilocybin

experimental

Migraine participants randomized to receive 10 mg psilocybin (oral).

Interventions

  • Psilocybin10 mg
    via Oral• single dose

    Synthetic psilocybin 10 mg (oral).

Migraine placebo (THC)

inactive

Migraine participants randomized to receive 2.5 mg THC (oral) as placebo comparator.

Interventions

  • Placebo2.5 mg
    via Oral• single dose

    Synthetic THC 2.5 mg (active placebo described as 'Placebo').

Healthy psilocybin

experimental

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

Interventions

  • Psilocybin10 mg
    via Oral• single dose

    Synthetic psilocybin 10 mg (oral).

Healthy placebo (THC)

inactive

Healthy control participants randomized to receive 2.5 mg THC (oral) as placebo comparator.

Interventions

  • Placebo2.5 mg
    via Oral• single dose

    Synthetic THC 2.5 mg (active placebo described as 'Placebo').

Participants

Ages
21 – 70
Sexes
Male & Female

Inclusion Criteria

  • Inclusion criteria:
  • Age 21 to 70 (inclusive)
  • Migraine disease per ICHD-3 criteria (for migraine participants) OR Healthy control participant

Exclusion Criteria

  • Exclusion criteria:
  • 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
  • Use of triptans or ditans more than twice weekly on average
  • Use of chronic serotonergic preventive therapies in the past 6 weeks
  • Use of preventive or transitional treatments that produce spikes and waning of symptom relief (e.g., botulinum toxin, CGRP antibodies, peripheral nerve/ganglion blocks, chiropractic manipulation)
  • History of a bleeding disorder or current anticoagulant use
  • Use of NSAIDs in the 7 days before PET scan and 7 days after PET scan

Study Details

Locations

VA Connecticut Healthcare System — West Haven, Connecticut, United States

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