{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:02:46Z","timestamp":1785420166155,"version":"3.56.0"},"reference-count":105,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T00:00:00Z","timestamp":1778284800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005888","name":"Medical University of Lodz","doi-asserted-by":"publisher","award":["503\/1-108-01\/503-11-001"],"award-info":[{"award-number":["503\/1-108-01\/503-11-001"]}],"id":[{"id":"10.13039\/501100005888","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005888","name":"Medical University of Lodz","doi-asserted-by":"publisher","award":["503\/1-156-06\/503-11-01"],"award-info":[{"award-number":["503\/1-156-06\/503-11-01"]}],"id":[{"id":"10.13039\/501100005888","id-type":"DOI","asserted-by":"publisher"}]},{"award":["503\/1-108-01\/503-11-001"],"award-info":[{"award-number":["503\/1-108-01\/503-11-001"]}],"id":[{"id":"https:\/\/ror.org\/02t4ekc95","id-type":"ROR","asserted-by":"publisher"}]},{"award":["503\/1-156-06\/503-11-01"],"award-info":[{"award-number":["503\/1-156-06\/503-11-01"]}],"id":[{"id":"https:\/\/ror.org\/02t4ekc95","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Aging is associated with chronic, low-grade inflammation (\u201cinflammaging\u201d), which contributes to neuropsychiatric and neurodegenerative disorders such as depression, Alzheimer\u2019s disease, and Parkinson\u2019s disease. Conventional pharmacotherapies often provide limited benefit in older adults and are further complicated by polypharmacy and drug\u2013drug interactions. Psilocybin, a serotonergic psychedelic acting primarily as a partial agonist at the 5-HT2A receptor and currently undergoing accelerated clinical development, has emerged as a potential multimodal therapeutic agent addressing these challenges. Acting via its active metabolite psilocin, 5-HT2A receptor-mediated signaling modulates cortical glutamatergic transmission, enhances tropomyosin receptor kinase B\/brain-derived neurotrophic factor (TrkB\/BDNF) pathways, and modulates neuroimmune cascades (includingnuclear factor kappa B (NF-\u03baB), with convergent systems-level effects such as reorganization of the default mode network. Human studies report acute reductions in TNF-\u03b1 with variable effects on IL-6 and CRP, consistent with an immunomodulatory profile. Pharmacokinetically, psilocybin shows properties advantageous in geriatric care: rapid onset, short half-life, and predominant phase-II glucuronidation, reducing interaction risk. Controlled studies demonstrate rapid antidepressant and anxiolytic effects in major depressive disorder, treatment-resistant depression, and existential distress, with emerging feasibility signals in neurodegeneration. Together, these findings support the hypothesis that a time-limited, mechanism-based intervention may improve mood and cognition while attenuating inflammation. This review integrates current evidence on psilocybin\u2019s neuroimmune and pharmacokinetic mechanisms relevant to aging, outlining its potential role in inflammation-related disorders and highlighting the need for targeted studies in older adults, who remain underrepresented in psychedelic research.<\/jats:p>","DOI":"10.3390\/ijms27104229","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T07:49:09Z","timestamp":1778572149000},"page":"4229","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Psilocybin in Older Adults: Therapeutic Opportunities in Inflammation-Driven Disorders of Aging\u2014From Depression to Neurodegeneration"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9032-1438","authenticated-orcid":false,"given":"Marta","family":"J\u00f3\u017awiak-B\u0119benista","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Medical University of Lodz, Zeligowskiego 7\/9, 90-752 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2225-7312","authenticated-orcid":false,"given":"Anna","family":"Stasiak","sequence":"additional","affiliation":[{"name":"Department of Hormone Biochemistry, Medical University of Lodz, Zeligowskiego 7\/9, 90-752 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9823-4176","authenticated-orcid":false,"given":"Monika","family":"Sienkiewicz","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Microbiology and Microbiological Diagnostic, Medical University of Lodz, Muszynskiego 1, 90-151 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0016-0541","authenticated-orcid":false,"given":"Pawe\u0142","family":"Kwiatkowski","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Immunology, Pomeranian Medical University in Szczecin, Powsta\u0144c\u00f3w Wielkopolskich 72, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2250-6040","authenticated-orcid":false,"given":"Edward","family":"Kowalczyk","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Medical University of Lodz, Zeligowskiego 7\/9, 90-752 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,9]]},"reference":[{"key":"ref_1","unstructured":"(2025, August 27). 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