{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:24:03Z","timestamp":1785425043956,"version":"3.56.0"},"reference-count":195,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Brain Science and Brain-like Intelligence Technology-National Science and Technology Major Project","award":["2025ZD0214904"],"award-info":[{"award-number":["2025ZD0214904"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82571390"],"award-info":[{"award-number":["82571390"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82271249"],"award-info":[{"award-number":["82271249"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"award":["82571390"],"award-info":[{"award-number":["82571390"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"award":["82271249"],"award-info":[{"award-number":["82271249"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Chronic pain is a complex disorder of central nervous system maladaptation, perpetuated not only by ascending nociceptive transmission but also by entrenched prior expectations. Conventional analgesics typically fail to reverse this cognitive rigidity and the ensuing pathological cycles. Classic psychedelics, however, are emerging as a promising avenue to help address this therapeutic impasse. This narrative review provides a comprehensive overview of the emerging science of psychedelics, encompassing their biological binding targets, potential neural mechanisms and clinical applications, in the context of chronic pain. We synthesize the therapeutic potential of classic psychedelics and critically examine the discrepancies between clinical outcomes and foundational mechanistic research. Furthermore, we evaluate key translational barriers, particularly compromised blinding and expectancy bias, and highlight the necessity for developing novel validation strategies. Ultimately, these new insights compel a fundamental rethinking of how biological neuroplasticity and subjective psychological experiences independently or synergistically drive analgesia, thereby offering a paradigm-shifting perspective for the translation of psychedelics into evidence-based analgesic therapeutics.<\/jats:p>","DOI":"10.3390\/molecules31152611","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T09:47:41Z","timestamp":1785145661000},"page":"2611","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Classic Psychedelics for Treating Chronic Pain: Mechanism and Clinical Translation"],"prefix":"10.3390","volume":"31","author":[{"given":"Hongyu","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu 610000, China"},{"name":"Laboratory of Anesthesia and Critical Care Medicine, National-Local Joint Engineering Research Center of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University, Chengdu 610000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bowen","family":"Ke","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu 610000, China"},{"name":"Laboratory of Anesthesia and Critical Care Medicine, National-Local Joint Engineering Research Center of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University, Chengdu 610000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5322-6802","authenticated-orcid":false,"given":"Ruotian","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu 610000, China"},{"name":"Laboratory of Anesthesia and Critical Care Medicine, National-Local Joint Engineering Research Center of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University, Chengdu 610000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1097\/j.pain.0000000000001384","article-title":"Chronic pain as a symptom or a disease: The IASP Classification of Chronic Pain for the International Classification of Diseases (ICD-11)","volume":"160","author":"Treede","year":"2019","journal-title":"Pain"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1038\/nrn3516","article-title":"Cognitive and emotional control of pain and its disruption in chronic pain","volume":"14","author":"Bushnell","year":"2013","journal-title":"Nat. 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