• Isabella Henderson, Ronnie Elsaadany, Gabriel Chan, Vikram Bajaj, Diana Duarte, Sadie Goodman, Michael Grunstein, Nehal P Vadhan, and Robert A Duarte.
• Northwell Health Department of Neurology, New York, NY, USA. ihenderson1@northwell.edu.
• Curr Pain Headache Rep. 2025 Jan 16; 29 (1): 2828.

Purpose Of ReviewExploration of the potential of serotonergic psychedelic drugs, such as psilocybin and LSD, as potential treatments for headache disorders. This review addresses the need for well-informed physician guidelines and discusses mechanisms, safety, and efficacy of these treatments. Further research, including the consideration of combination with psychotherapy, is needed.Recent FindingsPsychedelics demonstrate promising outcomes as treatments for headache disorders. Recent findings indicated that some patients who underwent brief periods of treatment with psychedelics experienced a reduction in headache attack frequency, severity, or duration. When prescription medications are ineffective at treating headache disorders, or are habit-forming, patients often turn to alternative options. There is anecdotal evidence that psychedelic drugs like LSD and psilocybin can effectively treat and prevent pain in patients with headache disorders, such as migraine or cluster headache. It is vital that physicians treating patients who self-treat with psychedelics be well-informed about the mechanisms and their effects to best advise their patients and coordinate their care well. This is a review assessing the literature on the mechanisms, safety, and efficacy of psychedelic drugs as a headache management intervention. We believe there is evidence that may support further investigation into the clinical use of psychedelic medications to treat cluster headache and migraine, including the consideration of use in conjunction with other interventions like cognitive behavioral therapy or acceptance and commitment training.© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

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