• Robert H Dworkin, Brian T Anderson, Nick Andrews, Robert R Edwards, Charles S Grob, Stephen Ross, Theodore D Satterthwaite, and Eric C Strain.
• Departments of Anesthesiology and Perioperative Medicine, Neurology, and Psychiatry, and Center for Health + Technology, University of Rochester School of Medicine and Dentistry, Rochester, New York. Electronic address: robert_dworkin@urmc.rochester.edu.
• J Pain. 2022 Oct 1; 23 (10): 166616791666-1679.

AbstractPsychedelic substances have played important roles in diverse cultures, and ingesting various plant preparations to evoke altered states of consciousness has been described throughout recorded history. Accounts of the subjective effects of psychedelics typically focus on spiritual and mystical-type experiences, including feelings of unity, sacredness, and transcendence. Over the past 2 decades, there has been increasing interest in psychedelics as treatments for various medical disorders, including chronic pain. Although concerns about adverse medical and psychological effects contributed to their controlled status, contemporary knowledge of psychedelics suggests that risks are relatively rare when patients are carefully screened, prepared, and supervised. Clinical trial results have provided support for the effectiveness of psychedelics in different psychiatric conditions. However, there are only a small number of generally uncontrolled studies of psychedelics in patients with chronic pain (eg, cancer pain, phantom limb pain, migraine, and cluster headache). Challenges in evaluating psychedelics as treatments for chronic pain include identifying neurobiologic and psychosocial mechanisms of action and determining which pain conditions to investigate. Truly informative proof-of-concept and confirmatory randomized clinical trials will require careful selection of control groups, efforts to minimize bias from unblinding, and attention to the roles of patient mental set and treatment setting. PERSPECTIVE: There is considerable promise for the use of psychedelic therapy for pain, but evidence-based recommendations for the design of future studies are needed to ensure that the results of this research are truly informative.Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

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