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This review primarily explores the utility of preclinical animal models in investigating the potential of psilocybin as an anti\u2010nociceptive agent. Initial studies involving psilocybin in animal models of neuropathic and inflammatory pain are summarised, alongside areas where further research is needed. The potential mechanisms of action, including targeting serotonergic pathways through the activation of 5\u2010HT\n                      <jats:sub>2A<\/jats:sub>\n                      receptors at both spinal and central levels, as well as neuroplastic actions that improve functional connectivity in brain regions involved in chronic pain, are considered. Current clinical aspects and the translational potential of psilocybin from animal models to chronic pain patients are reviewed. Also discussed is psilocybin's profile as an ideal anti\u2010nociceptive agent, with a wide range of effects against chronic pain and its associated inflammatory or emotional components.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>LINKED ARTICLES<\/jats:title>\n                    <jats:p>\n                      This article is part of a themed issue Emerging Therapeutic Opportunities for Psychedelic and Related Drugs. To view the other articles in this section visit\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v183.14\/issuetoc\">http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v183.14\/issuetoc<\/jats:ext-link>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.17420","type":"journal-article","created":{"date-parts":[[2024,11,29]],"date-time":"2024-11-29T23:39:32Z","timestamp":1732923572000},"page":"3992-4005","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Psilocybin as a novel treatment for chronic pain"],"prefix":"10.1111","volume":"183","author":[{"given":"Tate","family":"Askey","sequence":"first","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy University of Reading  Reading RG6 6UB UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reena","family":"Lasrado","sequence":"additional","affiliation":[{"name":"Compass Pathways  London W1F 0DQ UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0927-6567","authenticated-orcid":false,"given":"Maria","family":"Maiar\u00fa","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy University of Reading  Reading RG6 6UB UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8966-4238","authenticated-orcid":false,"given":"Gary J.","family":"Stephens","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy University of Reading  Reading RG6 6UB UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,29]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2008.12.021"},{"issue":"6","key":"e_1_2_11_3_1","first-page":"619","article-title":"Hallucinogenic indoleamines: Preferential action upon presynaptic serotonin receptors","volume":"1","author":"Aghajanian G. 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