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From Taboo to Treatment: The Emergence of Psychedelics in the Management of Pain and Opioid Use Disorder
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  • Jeremy Weleff,
  • Julio Nunes,
  • Gabriel Costa,
  • Mehmet Sofuoglu,
  • R. Ross Maclean,
  • Joao P. De Aquino
Jeremy Weleff
Yale University

Corresponding Author:jeremy.weleff@yale.edu

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Julio Nunes
Yale University
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Gabriel Costa
Universidade de Ribeirao Preto
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Mehmet Sofuoglu
Yale University
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R. Ross Maclean
Yale University
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Joao P. De Aquino
Yale University
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Abstract

The rise of psychedelics in contemporary medicine has sparked interest in their potential therapeutic applications. While traditionally associated with countercultural movements and recreational use, recent research has shed light on the potential benefits of psychedelics in various mental health conditions. In this review, we explore the emerging role of psychedelics in the management of chronic pain and opioid use disorder (OUD), two critical areas in need of innovative treatment options. Pain control remains a significant clinical challenge, particularly for individuals with OUD and those who receive long-term opioid therapy (LTOT) who develop marked tolerance to opioid-induced analgesia. Despite the magnitude of this problem, there is a scarcity of controlled studies investigating pain management alternatives for these populations. Drawing from preclinical and human evidence, we highlight the potential of psychedelics to act on shared neurobiological substrates of chronic pain and opioid use disorder, potentially reversing pain- and opioid-induced neuroadaptations, such as central sensitization. We elaborate on the multifaceted dimensions of the pain experience (sensory, affective, and cognitive) and their intersections that overlap with opioid-related phenomena (opioid craving and withdrawal), hypothesizing how these processes can be modulated by psychedelics. After summarizing the available clinical research, we propose mechanistic insights and methodological considerations for the design of future translational studies and clinical trials, building on a shared clinical and neurobiological understanding of chronic pain and OUD. Our intention is to provide timely perspectives that accelerate the development and exploration of novel therapeutics for chronic pain and OUD amidst the escalating opioid crisis.
30 Oct 2023Submitted to British Journal of Clinical Pharmacology
30 Oct 2023Submission Checks Completed
30 Oct 2023Assigned to Editor
07 Nov 2023Review(s) Completed, Editorial Evaluation Pending
09 Nov 2023Reviewer(s) Assigned
07 Feb 2024Review(s) Completed, Editorial Evaluation Pending