Comparing single‐ and repeat‐dose psilocybin with active placebo for migraine prevention in an exploratory randomized controlled clinical trial
Headache The Journal of Head and Face Pain December 29, 2025 Emmanuelle A. D. Schindler, Christopher Gottschalk, Brian P. 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.