Emmanuelle A. D. Schindler

Emmanuelle A. D. Schindler

Yale School of Medicine

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


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.


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 [1-3].  Methods—In an ongoing double-blind, placebo-controlled exploratory study, patients with migraine headache receive oral placebo and psilocybin two weeks apart under an enhanced blinding procedure. Headache diaries are maintained by subjects; physiological and psychological effects are monitored during sessions and several follow-up contacts are carried out. Results—Data from 9 subjects who received placebo and 0.143mg/kg psilocybin are presented. In the two weeks after psilocybin administration, migraine attack frequency (p=0.0148), pain severity (p=0.0006), and associated functional impairment (p=0.0069) were significantly reduced from baseline. Psychotropic drug effects were produced acutely with both placebo and psilocybin and did not correlate with changes in migraine burden. Subjects tolerated study procedures without unexpected or serious adverse events.  Conclusion—Within the limits of this exploratory study, preliminary analysis showed that a single low oral dose of psilocybin reduced migraine burden over 2 weeks. These findings support anecdotal reports in headache disorders, as well as clinical research in neuropsychiatric disease [4], that psilocybin has sustained therapeutic effects after limited dosing. The mechanism by which lasting effects are achieved in migraine headache remains unknown, though there are several known neurobiological effects of psychedelics relevant to headache disorders [5].  There are no conflicts of interest to disclose. This study was funded by institutional departmental funds, Heffter Research Institute, and Cluster Headache-Trigeminal Autonomic Cephalalgia.



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