This interventional trial (n=50) will explore mechanisms of psilocybin in migraine and healthy controls using a randomized, parallel, quadruple-blind design with oral psilocybin 10 mg versus 2.5 mg THC control.
Randomized, parallel-group study comparing a single oral 10 mg dose of psilocybin with a 2.5 mg THC control in migraine patients and healthy controls to probe mechanisms underlying reduced headache burden observed in prior work.
Outcomes include resting-state fMRI, SV2A PET for synaptic density, peripheral inflammatory markers, actigraphy for circadian rhythms, and sleep EEG measured before and one week after dosing.
Migraine participants randomized to receive 10 mg psilocybin (oral).
Synthetic psilocybin 10 mg (oral).
Migraine participants randomized to receive 2.5 mg THC (oral) as placebo comparator.
Synthetic THC 2.5 mg (active placebo described as 'Placebo').
Healthy control participants randomized to receive 10 mg psilocybin (oral).
Synthetic psilocybin 10 mg (oral).
Healthy control participants randomized to receive 2.5 mg THC (oral) as placebo comparator.
Synthetic THC 2.5 mg (active placebo described as 'Placebo').