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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 possible role of psychedelics in the management of chronic pain and opioid use disorder (OUD), 2 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\u2010term opioid therapy who develop marked tolerance to opioid\u2010induced 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 OUD, potentially reversing pain\u2010 and opioid\u2010induced 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\u2010related 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.<\/jats:p>","DOI":"10.1111\/bcp.16045","type":"journal-article","created":{"date-parts":[[2024,4,17]],"date-time":"2024-04-17T04:30:40Z","timestamp":1713328240000},"page":"3036-3053","source":"Crossref","is-referenced-by-count":11,"title":["From taboo to treatment: The emergence of psychedelics in the management of pain and opioid use disorder"],"prefix":"10.1111","volume":"90","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8071-7412","authenticated-orcid":false,"given":"Jeremy","family":"Weleff","sequence":"first","affiliation":[{"name":"Department of Psychiatry Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9622-3361","authenticated-orcid":false,"given":"Julio C.","family":"Nunes","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8702-5436","authenticated-orcid":false,"given":"Gabriel P. 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