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However, both ketamine and psychedelics are known to induce acute mystical experiences; ketamine can cause dissociative symptoms such as out-of-body experience, while psychedelics typically bring about hallucinogenic experiences, like a profound sense of unity with the universe or nature. The role of these mystical experiences in enhancing the antidepressant outcomes for patients with depression is currently an area of ongoing investigation and debate. Clinical studies have shown that the dissociative symptoms following the administration of ketamine or (<jats:italic>S<\/jats:italic>)-ketamine (esketamine) are not directly linked to their antidepressant properties. In contrast, the antidepressant potential of (<jats:italic>R<\/jats:italic>)-ketamine (arketamine), thought to lack dissociative side effects, has yet to be conclusively proven in large-scale clinical trials. Moreover, although the activation of the serotonin 5-HT<jats:sub>2A<\/jats:sub> receptor is crucial for the hallucinogenic effects of psychedelics in humans, its precise role in their antidepressant action is still under discussion. This article explores the importance of mystical experiences in enhancing the antidepressant efficacy of both ketamine and classic psychedelics.<\/jats:p>","DOI":"10.1007\/s00406-024-01770-7","type":"journal-article","created":{"date-parts":[[2024,2,27]],"date-time":"2024-02-27T05:02:13Z","timestamp":1709010133000},"page":"1333-1346","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Are \u201cmystical experiences\u201d essential for antidepressant actions of ketamine and the classic psychedelics?"],"prefix":"10.1007","volume":"275","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8892-0439","authenticated-orcid":false,"given":"Kenji","family":"Hashimoto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,2,27]]},"reference":[{"issue":"8","key":"1770_CR1","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1016\/s0006-3223(03)00231-2","volume":"53","author":"M Fava","year":"2003","unstructured":"Fava M (2003) Diagnosis and definition of treatment-resistant depression. 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Dr. Hashimoto is the inventor of filed patent applications on \u201cThe use of R-Ketamine in the treatment of psychiatric diseases,\u201d \u201c(S)-norketamine and salt thereof as pharmaceutical,\u201d \u201cR-Ketamine and derivative thereof as prophylactic or therapeutic agent for neurodegeneration disease or recognition function disorder,\u201d \u201cPreventive or therapeutic agent and pharmaceutical composition for inflammatory diseases or bone diseases,\u201d and \u201cR-Ketamine and its derivatives as a preventive or therapeutic agent for a neurodevelopmental disorder\u201d by the Chiba University. Dr. Hashimoto has also received speakers\u2019 honoraria, consultant fee, or research support from Abbott, Boehringer-Ingelheim, Daiichi-Sankyo, Meiji Seika Pharma, Seikagaku Corporation, Dainippon-Sumitomo, Taisho, Otsuka, Murakami Farm, and Perception Neuroscience.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interest"}}]}}