Exploratory Controlled Study of the Migraine-Suppressing Effects of Psilocybin
This double-blind, placebo-controlled, cross-over study (n=10) finds that a medium dose of psilocybin (10mg/70kg) significantly reduced migraines (headaches) in the two weeks after dosing.
Authors
- Nicholas Cozzi
- Deepak Cyril D’Souza
- Emmanuelle Schindler
Published
Abstract
While anecdotal evidence suggests that select 5-hydroxytryptamine 2A (5-HT2A) receptor ligands, including psilocybin, may have long-lasting therapeutic effects after limited dosing in headache disorders, controlled investigations are lacking. In an exploratory double-blind, placebo-controlled, cross-over study, adults with migraine received oral placebo and psilocybin (0.143 mg/kg) in 2 test sessions spaced 2 weeks apart. Subjects maintained headache diaries starting 2 weeks before the first session until 2 weeks after the second session. Physiological and psychological drug effects were monitored during sessions and several follow-up contacts with subjects were carried out to assure safety of study procedures. Ten subjects were included in the final analysis. Over the 2-week period measured after single administration, the reduction in weekly migraine days from baseline was significantly greater after psilocybin (mean, - 1.65 (95% CI: - 2.53 to - 0.77) days/week) than after placebo (- 0.15 (- 1.13 to 0.83) days/week; p = 0.003, t(9) = 4.11). Changes in migraine frequency in the 2 weeks after psilocybin were not correlated with the intensity of acute psychotropic effects during drug administration. Psilocybin was well-tolerated; there were no unexpected or serious adverse events or withdrawals due to adverse events. This exploratory study suggests there is an enduring therapeutic effect in migraine headache after a single administration of psilocybin. The separation of acute psychotropic and lasting therapeutic effects is an important finding, urging further investigation into the mechanism underlying the clinical effects of select 5-HT2A receptor compounds in migraine and other neuropsychiatric conditions.
Research Summary of 'Exploratory Controlled Study of the Migraine-Suppressing Effects of Psilocybin'
Introduction
Migraine is a highly prevalent and disabling neurological disorder for which existing treatments often have limited efficacy or undesirable side effects. Earlier anecdotal and some clinical reports have suggested that agonists at the 5-hydroxytryptamine 2A (5-HT2A) receptor, including psilocybin and LSD, can produce long-lasting reductions in headache burden after a single or a few oral doses, a pattern distinct from most conventional migraine preventives. However, controlled investigations of psilocybin in headache disorders have been lacking. Schindler and colleagues undertook an exploratory, proof-of-concept study to test whether a single low oral dose of psilocybin would suppress migraine frequency over the subsequent two-week period and to assess safety in a controlled setting. The study used a double-blind, placebo-controlled, cross-over framework, with the aim of informing future, larger trials and mechanistic work if signals of efficacy were observed.
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Study Details
- Study Typeindividual
- Journal
- Compound
- Topics
- Authors
- APA Citation
Schindler, E. A., Sewell, R. A., Gottschalk, C. H., Luddy, C., Flynn, L. T., Lindsey, H., Pittman, B. P., Cozzi, N. V., & D'Souza, D. C. (2021). Exploratory Controlled Study of the Migraine-Suppressing Effects of Psilocybin. Neurotherapeutics, 18(1), 534-543. https://doi.org/10.1007/s13311-020-00962-y
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