{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T14:53:19Z","timestamp":1785768799715,"version":"3.56.0"},"reference-count":320,"publisher":"Cambridge University Press (CUP)","license":[{"start":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T00:00:00Z","timestamp":1753401600000},"content-version":"unspecified","delay-in-days":205,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["cambridge.org"],"crossmark-restriction":true},"short-container-title":["Acta Neuropsychiatr."],"published-print":{"date-parts":[[2025]]},"abstract":"<jats:title>Abstract<\/jats:title>\n\t  <jats:sec id=\"S0924270825100306_as1\">\n\t    <jats:title>Objective:<\/jats:title>\n\t    <jats:p>By synthesising findings from both clinical and preclinical research, this review aims to provide an understanding of the interplay between 5-HT2A receptor psychedelics and the immune system and considers how their immunomodulatory effects associate with neuronal and behavioural changes.<\/jats:p>\n\t  <\/jats:sec>\n\t  <jats:sec id=\"S0924270825100306_as2\">\n\t    <jats:title>Methods:<\/jats:title>\n\t    <jats:p>A PubMed literature search covering the past 30 years was conducted using keywords such as \u20185-HT2A receptor\u2019, \u2018psychedelics\u2019, \u2018immune system\u2019, and \u2018HPA axis\u2019. Studies were included if they addressed the effects of 5-HT2AR psychedelics on immune function, neuroimmune interactions, or HPA axis involvement. This narrative review synthesises evidence highlighting the bi-directional effects of 5-HT2AR psychedelics between the immune and nervous systems, identified through this search process.<\/jats:p>\n\t  <\/jats:sec>\n\t  <jats:sec id=\"S0924270825100306_as3\">\n\t    <jats:title>Results:<\/jats:title>\n\t    <jats:p>Preclinical and clinical studies report that 5-HT2AR psychedelics have some direct immunomodulatory properties with downregulation of gene regulators like NF-\u03baB, and reduced cytokine expression such as TNF-\u03b1, IL-6, and IL-1\u03b2 at a central and peripheral level, accompanied by modulation of corticotrophin releasing hormone (CRH), adrenocorticotrophic hormone (ACTH), and cortisol. Direct immunomodulatory effects are mediated by pathways involving serotonin receptors, the Sigma-1 receptor, and the TrkB receptor. Immunomodulation is further mediated indirectly via the HPA axis.<\/jats:p>\n\t  <\/jats:sec>\n\t  <jats:sec id=\"S0924270825100306_as4\">\n\t    <jats:title>Conclusion:<\/jats:title>\n\t    <jats:p>Further studies will determine the molecular and cellular mechanisms underlying these immunomodulatory effects. There is growing interest in the potential of 5-HT2AR psychedelics for treating a range of mental health and brain disorders. In keeping with their immunomodulatory actions, the likely modulation of brain glia and glial-neuronal interaction remains to be determined, representing a promising direction of further research on the therapeutic potential of 5-HT2AR psychedelics.<\/jats:p>\n\t  <\/jats:sec>","DOI":"10.1017\/neu.2025.10030","type":"journal-article","created":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T09:30:24Z","timestamp":1753435824000},"update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":7,"title":["Narrating the psychoneuroimmunomodulatory properties of serotonin 5-HT<sub>2A<\/sub> receptor psychedelics from a transdiagnostic perspective"],"prefix":"10.1017","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3391-5293","authenticated-orcid":false,"given":"Guillaume","family":"Thuery","sequence":"first","affiliation":[{"name":"Tallaght University Hospital and Trinity College Dublin"},{"name":"Trinity College 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