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.
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.