Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics
January 1, 2021
Emmanuelle A. D. Schindler, R Andrew Sewell, Christopher Gottschalk et al.
138 citations
In a small exploratory double-blind, placebo-controlled, cross-over study, ten adults with migraine received a single oral dose of psilocybin (0.143 mg/kg) or placebo, with sessions two weeks apart. Over the two weeks following administration, psilocybin reduced weekly migraine days by an average of 1.65 days (95% CI: -2.53 to -0.77), significantly more than placebo, which reduced them by 0.15 days (95% CI: -1.13 to 0.83). The reduction in migraine frequency was not linked to the intensity of acute psychedelic effects. Psilocybin was well-tolerated with no serious adverse events. The findings suggest a lasting therapeutic benefit from a single dose, independent of acute psychological effects.
Journal of Psychoactive Drugs
October 20, 2015
Emmanuelle A. D. Schindler, Christopher Gottschalk, Marsha J. Weil et al.
104 citations
Cluster headache is one of the most debilitating pain syndromes, and many patients do not respond to standard treatments. A survey of 496 people with cluster headache, recruited from websites and clinics, found that the indoleamine hallucinogens psilocybin, lysergic acid diethylamide, and lysergic acid amide were rated as comparable to or more effective than most conventional medications for aborting attacks and preventing them. These substances were also perceived to shorten or abort a cluster period and bring chronic cluster headache into remission more often than conventional medications. Even infrequent, non-hallucinogenic doses were reported as effective. The findings reinforce the need for further controlled studies of these compounds.
Headache The Journal of Head and Face Pain
November 1, 2022
Christina Luddy, Yutong Zhu, Hayley Lindsey et al.
75 citations
In an exploratory randomized, double-blind, placebo-controlled trial, a pulse regimen of three doses of psilocybin (0.143 mg/kg) given about five days apart did not significantly reduce cluster headache attack frequency compared to placebo. Over three weeks, attack frequency changed by −3.2 attacks per week with psilocybin (baseline 9.6) and 0.03 attacks per week with placebo (baseline 8.9), a difference that was not statistically significant. The overall effect size was moderate (d = 0.69), but large in chronic participants (d = 1.25) and small in episodic participants (d = 0.35). Changes in attack frequency were not linked to the intensity of acute psychedelic effects. Psilocybin was well-tolerated with no serious adverse events.
Journal of the Neurological Sciences
May 15, 2024
Emmanuelle A. D. Schindler, R Andrew Sewell, Christopher Gottschalk et al.
37 citations
In a blinded extension of a prior randomized trial, ten people with cluster headache received a second round of three doses of psilocybin (10 mg/70 kg, five days apart) at least six months after their first round. Attack frequency dropped significantly from a baseline of 18.4 attacks per week to 9.8 attacks per week in the three weeks after the first dose, a reduction of about 50%. This benefit occurred regardless of whether the participant had responded to psilocybin in the first round. No serious or unexpected adverse events occurred. The findings suggest that repeating a pulse of psilocybin can substantially reduce cluster headache attacks and that prior response does not predict the effect of retreatment.
Neurology
April 7, 2025
Emmanuelle A. D. Schindler, Christopher Gottschalk, Deepak Cyril D’souza
2 citations
In clinical trials of psilocybin for migraine and cluster headache, the strength of acute psychedelic effects did not predict reductions in headache frequency. Improvements in mental health measures were also not consistently linked to headache relief. The findings suggest that the therapeutic benefits of psilocybin on headache disorders may operate through mechanisms separate from its psychedelic or mood-altering properties.
Headache The Journal of Head and Face Pain
December 29, 2025
Emmanuelle A. D. Schindler, Christopher Gottschalk, Brian Pittman et al.
1 citation
In an exploratory randomized, double-blind, placebo-controlled trial, adults with migraine received either two doses of diphenhydramine placebo, one dose of psilocybin (10 mg) plus one dose of diphenhydramine, or two doses of psilocybin, each separated by 7 days. Over the two weeks after the sessions, the reduction in migraine days per week did not differ significantly among groups, though large effect sizes were seen for those receiving psilocybin. Over eight weeks, all groups showed similar reductions in migraine frequency of about 50%. Diphenhydramine partially mimicked psilocybin's acute effects, but blinding was incomplete. No serious adverse events occurred.