Adapting psychedelic medicine for headache and chronic pain disorders

ABSTRACT

Introduction

While the majority of current research and development surrounds depression, demoralization, and substance use disorders, there are numerous reports of psychedelics having beneficial effects in other branches of medicine, including for headache disorders and chronic pain.

Areas covered

This perspective reviews conventional forms of treatment for headache and other chronic pain disorders and describes historical, recent, and ongoing investigations of the therapeutic effects of psychedelics in these disorders. The first two clinical trials of psilocybin in headache disorders and recent case reports of psilocybin mushroom self-administration in chronic pain patients are described. This perspective highlights several factors related to the application of psychedelics in chronic pain disorders, comparing this with the standard psychedelic-assisted psychotherapy model of treatment.

Expert opinion

When faced with a more constricted view of psychedelic medicine that features larger doses, underscores subjective effects in the mediation of therapeutic outcomes, and requires adjunctive psychotherapy to ensure safety and efficacy, the application of psychedelics in headache and chronic pain disorders may face challenges. It will be important to allow for flexibility and adaptation in protocols to evaluate different treatment paradigms, mechanisms of action, and the range of pharmacologic and extra-pharmacologic factors that affect psychedelic treatment outcomes.

KEYWORDS:

• headache disorders
• chronic pain
• pain disorders
• lysergic acid diethylamide
• psilocybin
• psychedelics
• transitional treatment

Article highlights

• Psychedelics have a long history of human interaction and are resurging as potential therapeutic agents, including in headache and chronic pain disorders.

• Some pain conditions, like headache disorders, might be especially responsive to smaller doses with subtle subjective effects.

• Acute subjective effects of psychedelics may not be associated with therapeutic outcomes or necessitate concomitant psychotherapy in headache disorders.

• The psychedelic-assisted therapy model commonly used in psychedelic research contains elements that may not be necessary or may even be counterproductive in headache and chronic pain disorders.

• Real-world implementation must be considered in developing protocols for psychedelic treatment of headache and chronic pain disorders.

Declaration of interest

EAD Schindler serves on the scientific advisory boards for Ceruvia Lifesciences and Clusterbusters and serves as a paid consultant for PureTech Health. She is named inventor on the following patents related to psychedelics in headache disorders: 17/168,638 (US); 2021709245 (EP); 3,166,785 (CA); 2022–547896 (JP). EAD Schindler is also an employee of the US Department of Veterans Affairs – any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the US Department of Veterans Affairs. PSH was previously in a paid advisory relationship with Silo Pharma and is currently in paid advisory relationships with the following organizations regarding the development of psychedelics and related compounds: Bright Minds Biosciences Ltd., Eleusis Benefit Corporation, Journey Colab Corporation, and Reset Pharmaceuticals Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

One reviewer was an employee of Lundbeck AS at the time of their review. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

EAD Schindler has received research funding from Ceruvia Lifesciences and the Wallace Research Foundation. She has also previously received research funding from Heffter Research Institute and Clusterbusters. PS Hendricks has received research funding from the National Institutes of Health and Heffter Research Institute.