This review (2021) makes the case for using psychedelics to treat pain. Key areas discussed include studies that have directly used psychedelics to treat pain, potential neuro-restorative effects of psychedelics in pain-related states of consciousness, anti-neuroinflammatory and pro-immunomodulatory actions of psychedelics and the safety, legal, and ethical consideration inherent in psychedelics’ pharmacotherapy. Psychedelics could also help to elucidate the mechanism of pain syndromes.

Abstract

“Basic pain research has shed light on key cellular and molecular mechanisms underlying nociceptive and phenomenological aspects of pain. Despite these advances, [we still yearn for] the discovery of novel therapeutic strategies to address the unmet needs of about 70% of chronic neuropathic pain patients whose pain fails to respond to opioids as well as to other conventional analgesic agents. Importantly, a substantial body of clinical observations over the past decade cumulatively suggests that the psychedelic class of drugs may possess heuristic value for understanding and treating chronic pain conditions. The present review presents a theoretical framework for hitherto insufficiently understood neuroscience-based mechanisms of psychedelics’ potential analgesic effects. To that end, searches of PubMed-indexed journals were performed using the following Medical Subject Headings’ terms: pain, analgesia, inflammatory, brain connectivity, ketamine, psilocybin, functional imaging, and dendrites. Recursive sets of scientific and clinical evidence extracted from this literature review were summarized within the following key areas: (1) studies employing psychedelics for alleviation of physical and emotional pain; (2) potential neuro-restorative effects of psychedelics to remediate the impaired connectivity underlying the dissociation between pain-related conscious states/cognitions and the subcortical activity/function leading to the eventual chronicity through immediate and long-term effects on dendritic plasticity; (3) anti-neuroinflammatory and pro-immunomodulatory actions of psychedelics as the may pertain to the role of these factors in the pathogenesis of neuropathic pain; (4) safety, legal, and ethical consideration inherent in psychedelics’ pharmacotherapy. In addition to direct beneficial effects in terms of reduction of pain and suffering, psychedelics’ inclusion in the analgesic armamentarium will contribute to deeper and more sophisticated insights not only into pain syndromes but also into frequently comorbid psychiatric conditions associated with emotional pain, e.g., depressive and anxiety disorders. Further inquiry is clearly warranted into the above areas that have potential to evolve into further elucidate the mechanisms of chronic pain and affective disorders, and lead to the development of innovative, safe, and more efficacious neurobiologically-based therapeutic approaches.”

Authors: Igor Elman, Amanda Pustilnik & David Borsook

Author Highlights:

• There is an unmet need for adequate treatment for chronic pain.

• Psychedelics offer a potential promise for such treatments through neurorestorative effects (dendritic sprouting) and anti-inflammatory effects.

• The utility of psychedelics for chronic pain needs to be rigorously evaluated through appropriate randomized controlled studies