Randomised, Phase I parallel study (n=18) testing single and repeated oral psilocybin (10 mg) vs diphenhydramine placebo across two sessions ~7 days apart to assess effects on migraine headache burden and mechanisms.
This randomised, parallel-design study evaluates up to two oral doses of psilocybin (10 mg) compared with diphenhydramine placebo in adults with migraine to assess clinical efficacy and biological mechanisms.
Neuroinflammatory markers relevant to migraine will be measured to explore potential anti-inflammatory mechanisms that may underlie clinical effects; outcomes will inform larger future trials.
Placebo at both sessions (placebo then placebo ~7 days apart).
25 mg diphenhydramine per session (placebo)
Placebo first, psilocybin second (~7 days apart).
Placebo (diphenhydramine) at session 1
10 mg psilocybin at session 2
Psilocybin first, placebo second (~7 days apart).
10 mg psilocybin at session 1
25 mg diphenhydramine at session 2
Psilocybin at both sessions (~7 days apart).
10 mg psilocybin per session