Scoping Review: The Role of Psychedelics in the Management of Chronic Pain

Abstract

Introduction

Amid a lack of effective chronic pain treatments, psychedelics have gained attention as a potential solution, although their Schedule 1 classification poses challenges. Psychedelics, such as lysergic acid diethylamide (LSD) and psilocybin, have gained popularity as alternatives and adjuncts for chronic pain treatment. Studies suggest that they may modulate pain processing through agonism primarily at the serotonin receptor, 5-HT_2A. One of the first of its nature, we present an artificial intelligence (AI)-powered scoping review primarily focusing on evaluating psychedelics for chronic pain conditions such as cluster headache, phantom limb pain, and fibromyalgia.

Methods

In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, we used an AI-powered comprehensive search strategy utilizing the ChatGPT4.0 Bing chat to search Medline, Embase, Cochrane, and Google Scholar for articles addressing chronic pain. The query was performed on June 1, 2023, focusing on psychedelics for chronic, non-cancer pain including headache disorders. Inclusion criteria were English-only, peer-reviewed articles involving human participants >18 years, focusing on chronic pain conditions (eg, phantom limb pain and cluster headache), using LSD, 2.5-dimethoxy-4-bromophenethylamine (2C-B), N, N-dimethyltryptamine (DMT), psilocybin, or mescaline. Exclusion criteria were reviews, editorials, and opinion articles and studies focusing on tetrahydrocannabinol/cannabis and/or ketamine.

Results

A total of 186 unique database entries were retrieved, of which nine studies were included in the scoping review. These included four case reports/series, an open-label study, a cohort study, two online surveys, and a randomized, double-blind, placebo-controlled trial. They comprised three studies addressing phantom limb pain, four addressing cluster headaches, and two addressing fibromyalgia, spinal cord injury, complex regional pain syndrome, and lumbar radiculopathy.

Conclusion

Psychedelics may have potential in alleviating pain symptoms secondary to a multitude of chronic pain conditions. However, further randomized, double-blind, placebo-controlled trials are needed to further explore and evaluate the role of psychedelics in chronic, non-cancer pain.

Keywords:

• psilocybin
• mescaline
• lysergic acid diethylamide
• headache
• phantom limb pain
• scoping review

Acknowledgment

Michael E Schatman, Vwaire Orhurhu, and Trent Emerick are co-senior authors for this study. We would like to thank Harvard Medical School Countway Librarian, Corey J. Purcell, BA MLIS, for his assistance in designing the initial search strategy for PubMed. The final acknowledgment goes to a special woman who believed when no one else would. Through her sweat and tears, the world is better off. May your sacrifice never be in vain, as we are here to treat pain.

Disclosure

Dr Christopher Robinson reports personal fees from TrueLearn, Doc2Doc, Augmend Health, outside the submitted work. Dr Michael Schatman is a research consultant for Modoscript, scientific steering committee for Collegium Pharma, and advisory committee for Syneos Health, outside the submitted work. Dr Trent Emerick reports stock/equity for Vanish Therapeutics, Inc, outside the submitted work. The authors report no other conflicts of interest in this work.