Yale School of Medicine

Emmanuelle A. D. Schindler

Preventive Effects of a Single Low Oral Dose of Psilocybin in Migraine Headache

Background—Patients with headache disorders have identified therapeutic effects from psychedelics, which in contrast to conventional therapies are anecdotally reported to produce lasting reductions in headache burden after a single or few doses. This study sought to formally investigate this effect.

Methods—In an ongoing double-blind, placebo-controlled pilot study, patients with migraine headache received oral placebo (microcrystalline cellulose) followed two weeks later by psilocybin (either 0.0143mg/kg or 0.143mg/kg). Migraine attacks were documented in a diary; vital signs, general drug effects, and psychedelic effects were measured during experimental sessions.

Results—At the time of this submission, data from 9 subjects who received placebo and 0.143mg/kg psilocybin are presented. This single psilocybin administration reduced migraine burden in the two weeks following experimental sessions, including attack frequency (P=0.007), pain severity (P=0.001), photophobia (P=0.046), and nausea (P=0.031). Psilocybin tended to delay the time to the next two migraine attacks (1st, P=0.189; 2nd, P=0.055). Neither psychedelic nor general drug effects were correlated with reductions in migraine burden. Subjects tolerated experimental procedures without unexpected or serious adverse events.

Conclusion—Within the limits of this pilot investigation, these findings suggest that a single, low dose of oral psilocybin effects a reduction in migraine burden over a 2-week period. These findings support anecdotal reports that psychedelics have sustained therapeutic effects in headache disorders after limited dosing. There are several known neurobiological effects of psilocybin and related compounds relevant to headache disorders. Additional study of these processes is warranted to understand the source of psilocybin’s unique effects.


Dr. Schindler is a board-certified Neurologist at Yale School of Medicine in New Haven, Connecticut. She has expertise in headache medicine and among her efforts to optimize the management of headache disorders, she has ongoing studies seeking to understand the effects and mechanisms of action of psilocybin in cluster, migraine, and post-traumatic headache. Previously, she studied the neuropharmacology of psychedelics and other serotonergic compounds in the context of receptor binding and intracellular signaling at Drexel University College of Medicine, where she received her Ph.D. (2010) and M.D. (2012). She has published and presented on the biochemical, behavioral, neuropharmacological, and neuroendocrinological effects of psychedelics. Dr. Schindler has also won several awards for academic excellence, has a number of publications and invited book chapters, and remains at the forefront of headache medicine.



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