Clinical TrialHeadache Disorders (Cluster & Migraine)PlaceboPlaceboPsilocybinPsilocybinPlaceboPsilocybinCompleted

Repeat Dosing of Psilocybin in Migraine Headache

Randomised, Phase I parallel study (n=18) testing single and repeated oral psilocybin (10 mg) vs diphenhydramine placebo across two sessions ~7 days apart to assess effects on migraine headache burden and mechanisms.

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

Detailed Description

This randomised, parallel-design study evaluates up to two oral doses of psilocybin (10 mg) compared with diphenhydramine placebo in adults with migraine to assess clinical efficacy and biological mechanisms.

Neuroinflammatory markers relevant to migraine will be measured to explore potential anti-inflammatory mechanisms that may underlie clinical effects; outcomes will inform larger future trials.

Study Protocol

Preparation

sessions

Dosing

2 sessions

Integration

sessions

Study Arms & Interventions

Placebo/Placebo

inactive

Placebo at both sessions (placebo then placebo ~7 days apart).

Interventions

  • Placebo25 mg
    via Oral• two sessions• 2 doses total

    25 mg diphenhydramine per session (placebo)

Placebo/Psilocybin

experimental

Placebo first, psilocybin second (~7 days apart).

Interventions

  • Placebo25 mg
    via Oral• single dose• 1 doses total

    Placebo (diphenhydramine) at session 1

  • Psilocybin10 mg
    via Oral• single dose• 1 doses total

    10 mg psilocybin at session 2

Psilocybin/Placebo

experimental

Psilocybin first, placebo second (~7 days apart).

Interventions

  • Psilocybin10 mg
    via Oral• single dose• 1 doses total

    10 mg psilocybin at session 1

  • Placebo25 mg
    via Oral• single dose• 1 doses total

    25 mg diphenhydramine at session 2

Psilocybin/Psilocybin

experimental

Psilocybin at both sessions (~7 days apart).

Interventions

  • Psilocybin10 mg
    via Oral• two sessions• 2 doses total

    10 mg psilocybin per session

Participants

Ages
21 – 65
Sexes
Male & Female

Inclusion Criteria

  • Diagnosis of migraine headache per ICHD-3 criteria
  • Typical pattern of migraine attacks with approximately two migraines or more weekly
  • Attacks are managed by means involving no more than twice weekly triptan use

Exclusion Criteria

  • Axis I psychotic or manic disorder (e.g., schizophrenia, bipolar I, depression with psychosis)
  • Axis I psychotic or manic disorder in first degree relative
  • Unstable medical condition; severe renal, cardiac, or hepatic disease; pacemaker; or serious central nervous system pathology
  • Pregnant, breastfeeding, lack of adequate birth control
  • History of intolerance to psilocybin, lysergic acid diethylamide (LSD), or related compounds
  • Drug abuse within the past 3 months (excluding tobacco)
  • Urine toxicology positive to drugs of abuse
  • Alcohol use of >21 drinks per week (males); >14 drinks per week (females; NIAAA guidelines)
  • Use of alcohol in the week prior to the first test day
  • Use of vasoconstrictive medications (i.e., sumatriptan, pseudoephedrine, midodrine) within 5 half-lives of test days
  • Use of serotonergic antiemetics (i.e., ondansetron) in the past 2 weeks
  • Use of antidepressant medication (i.e., TCA, MAOI, SSRI) in the past 6 weeks
  • Use of steroids or certain other immunomodulatory agents (i.e., azathioprine) in the past 2 weeks
  • Use of migraine onabotulinum toxin (i.e., Botox) or monoclonal antibodies against CGRP or its receptor (i.e., erenumab) in the past month or while therapeutic effects are still present

Study Details

Locations

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

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