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This critical review evaluates current evidence on psilocybin\u2019s efficacy, juxtaposing potential benefits with the practical aspects of psychedelic-assisted psychotherapy (PAP) and the methodological constraints of existing research.<\/jats:p><jats:p>An electronic literature search was conducted using PubMed\/MEDLINE, selecting studies published up to December 2023 that explored the clinical use of psilocybin in mood and anxiety disorders, obsessive-compulsive disorder, post-traumatic stress disorder, and substance use disorder. Despite promising preliminary results suggesting psilocybin\u2019s efficacy in alleviating depression and anxiety, as well as obsessions, compulsions, and addictive behaviors, significant evidence gaps persist. These include evaluating the efficacy of psilocybin compared to standard antidepressants or anxiolytic molecules and identifying patient subpopulations that might benefit most from PAP. Concerns about psilocybin\u2019s safety, long-term efficacy, and optimal dosage remain unclear due to previous trials\u2019 limitations. Real-world implementation faces challenges, including infrastructural requirements, personnel training, and unresolved legal and ethical issues. This paper argues for further research to substantiate the evidence base, emphasizing the need for larger studies that overcome current methodological limitations and explore psilocybin\u2019s full therapeutic potential. While psilocybin holds promise for psychiatry, its successful translation from research to clinical practice demands more robust evidence on efficacy, safety, and methodological rigor. In addition, other factors, such as cultural stigma and legal\/ethical issues, need to be successfully addressed to facilitate psilocybin\u2019s implementation in healthcare systems.<\/jats:p>","DOI":"10.1017\/s1092852924002268","type":"journal-article","created":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T10:16:48Z","timestamp":1733825808000},"page":"570-584","source":"Crossref","is-referenced-by-count":8,"title":["The revival of psilocybin between scientific excitement, evidence of efficacy, and real-world challenges"],"prefix":"10.1017","volume":"29","author":[{"given":"Mauro","family":"Scala","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Fabbri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Fusar-Poli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Di Lorenzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Ferrara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Amerio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Fusar-Poli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Pichiecchio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Asteggiano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Menchetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"De Ronchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"MNESYS - Mood and Psychosis Sub-Project (Spoke 5)","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7930-563X","authenticated-orcid":false,"given":"Giuseppe","family":"Fanelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4363-3759","authenticated-orcid":false,"given":"Alessandro","family":"Serretti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"56","published-online":{"date-parts":[[2024,12,10]]},"reference":[{"key":"S1092852924002268_r82","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychires.2023.03.031"},{"key":"S1092852924002268_r84","doi-asserted-by":"publisher","DOI":"10.1177\/0269881114548296"},{"key":"S1092852924002268_r35","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0229067"},{"key":"S1092852924002268_r79","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-017-4771-x"},{"key":"S1092852924002268_r1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2021.20101429"},{"key":"S1092852924002268_r68","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaclp.2020.12.011"},{"key":"S1092852924002268_r56","volume-title":"Dark Persuasion: A History of Brainwashing from Pavlov to Social Media","author":"Dimsdale","year":"2021"},{"key":"S1092852924002268_r23","doi-asserted-by":"publisher","DOI":"10.1177\/0269881119895520"},{"key":"S1092852924002268_r18","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.2.735"},{"key":"S1092852924002268_r65","doi-asserted-by":"publisher","DOI":"10.1037\/0033-2909.132.1.1"},{"key":"S1092852924002268_r31","doi-asserted-by":"publisher","DOI":"10.1001\/archgenpsychiatry.2010.116"},{"key":"S1092852924002268_r71","first-page":"CD005652","article-title":"Psychological therapies for people with borderline personality disorder","author":"Stoffers-Winterling","year":"2012","journal-title":"Cochrane Database Syst. 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