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 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.