Psilocybin for Headache Disorders (Cluster & Migraine)

1 paper and 7 clinical trials exploring psilocybin as a treatment for headache disorders (cluster & migraine).

CompoundClassic Psychedelic

Psilocybin

Psilocybin is a naturally occurring tryptamine psychedelic that acts as a prodrug to psilocin, a potent 5-HT2A receptor agonist. It is the furthest advanced psychedelic in clinical development, with two positive Phase III trials in treatment-resistant depression and expanding regulated access in Australia, Germany, and US states.

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IndicationOver 3 billion people globally.

Headache Disorders (Cluster & Migraine)

Psychedelics are being researched as potential treatments for headache disorders, including migraines and cluster headaches, which affect a significant portion of the global population. Early findings indicate that psychedelics may modulate pain perception and offer novel therapeutic pathways for those suffering from these debilitating conditions.

Full Headache Disorders (Cluster & Migraine) profile

Academic Research

1 paper

Open Accessindividual

Comparing single- and repeat-dose psilocybin with active placebo for migraine prevention in an exploratory randomized controlled clinical trial

In an exploratory randomised, double‑blind trial in adults with frequent migraine, single or two‑dose psilocybin produced reductions in migraine frequency similar to an active diphenhydramine placebo and no serious adverse events were observed. Incomplete blinding and nonsignificant between‑group differences despite large effect sizes in psilocybin arms indicate the need for larger, better‑controlled trials with headache‑specialist input to separate drug and non‑drug effects.

Published: December 29, 2025
Journal: Headache
Authors: Schindler, E. A. D., Gottschalk, C. H., Pittman, B. P., D'Souza, D. C.

Clinical Trials

7 trials

RecruitingPhase I

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.

Started: September 1, 2024
Type: interventional
Blinding: quadruple
Randomized: Yes
Registry ID: NCT06464367

CompletedPhase I

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.

Started: July 15, 2021
Type: interventional
Blinding: quadruple
Randomized: Yes
Registry ID: NCT04218539

TerminatedPhase I

Phase 1b Study in Patients With Short-Lasting Unilateral Neuralgiform Headache Attacks (SUNHA)

This exploratory open-label Phase Ib, ascending dose study evaluates the effects of psilocybin on cognition in patients with chronic SUNHA.

Started: May 21, 2021
Type: interventional
Blinding: none
Randomized: No
Registry ID: NCT04905121

TerminatedPhase I/II

Prophylactic Effects of Psilocybin on Chronic Cluster Headache

Open-label, single-group pilot study (n=10) assessing prophylactic effects of low-dose psilocybin (0.14 mg/kg oral) given in three weekly sessions for chronic cluster headache with fMRI and psilocin sampling.

Started: January 21, 2020
Type: interventional
Blinding: none
Randomized: No
Registry ID: NCT04280055

TerminatedPhase I

Effects of Psilocybin in Concussion Headache

Double-blind crossover trial (n=12) investigating repeated oral psilocybin (two sessions; low 0.0143 mg/kg or 1 mg and high 0.143 mg/kg or 10 mg) versus placebo for post-traumatic headache.

Started: March 28, 2019
Type: interventional
Blinding: double
Randomized: Yes
Registry ID: NCT03806985

CompletedPhase I

Psilocybin for the Treatment of Migraine Headache

Randomised, double-blind, crossover study (n=14) comparing low (0.0143 mg/kg) and high (0.143 mg/kg) oral psilocybin versus placebo in adults with migraine.

Started: January 11, 2017
Type: interventional
Blinding: double
Randomized: Yes
Registry ID: NCT03341689

Explore further

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