{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T03:02:22Z","timestamp":1792119742283,"version":"4.4.0"},"reference-count":91,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T00:00:00Z","timestamp":1730073600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Jack Brown and Family Alzheimer\u2019s Disease Research Foundation"},{"name":"Natural Sciences and Engineering Research Council of Canada"},{"name":"University of British Columbia Okanagan Campus"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Neuroinflammation that is caused by microglia, the main immune cells of the brain, contributes to neurodegenerative diseases. Psychedelics, including psilocybin and lysergic acid diethylamide (LSD), possess certain anti-inflammatory properties and, therefore, should be considered as drug candidates for treating neuroinflammatory pathologies. When ingested, psilocybin is rapidly dephosphorylated to yield psilocin, which crosses the blood\u2013brain barrier and exerts psychotropic activity by interacting with the 5-hydroxytryptamine 2A receptors (5-HT2ARs) on neurons. Since microglia express all three 5-HT2R isoforms, we hypothesized that, by interacting with these receptors, psilocin beneficially modulates select neuroimmune functions of microglia. We used microglia-like cell lines to demonstrate that psilocin, at non-toxic concentrations, did not affect the secretion of tumor necrosis factor (TNF) by immune-stimulated microglial cells, but significantly inhibited their phagocytic activity, the release of reactive oxygen species (ROS), and nitric oxide (NO) production. The inhibitory activity of psilocin on the latter two functions was similar to that of two selective 5-HT2R agonists, namely, 25I-NBOH and Ro60-0175. The role of this subfamily of receptors was further demonstrated by the application of 5-HT2R antagonists cyproheptadine and risperidone. Psilocin should be considered a novel drug candidate that might be effective in treating neuroimmune disorders, such as neurodegenerative diseases, where reactive microglia are significant contributors.<\/jats:p>","DOI":"10.3390\/molecules29215084","type":"journal-article","created":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T07:47:18Z","timestamp":1730101638000},"page":"5084","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Psilocin, the Psychoactive Metabolite of Psilocybin, Modulates Select Neuroimmune Functions of Microglial Cells in a 5-HT2 Receptor-Dependent Manner"],"prefix":"10.3390","volume":"29","author":[{"given":"Kennedy R.","family":"Wiens","sequence":"first","affiliation":[{"name":"Laboratory of Cellular and Molecular Pharmacology, Department of Biology, University of British Columbia Okanagan Campus, Kelowna, BC V1V 1V7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noah A. H.","family":"Brooks","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Pharmacology, Department of Biology, University of British Columbia Okanagan Campus, Kelowna, BC V1V 1V7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ishvin","family":"Riar","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Pharmacology, Department of Biology, University of British Columbia Okanagan Campus, Kelowna, BC V1V 1V7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8303-7743","authenticated-orcid":false,"given":"Bridget K.","family":"Greuel","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Pharmacology, Department of Biology, University of British Columbia Okanagan Campus, Kelowna, BC V1V 1V7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan A.","family":"Lindhout","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Pharmacology, Department of Biology, University of British Columbia Okanagan Campus, Kelowna, BC V1V 1V7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6587-6458","authenticated-orcid":false,"given":"Andis","family":"Klegeris","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Pharmacology, Department of Biology, University of British Columbia Okanagan Campus, Kelowna, BC V1V 1V7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1038\/s41593-020-0687-6","article-title":"Synergy between amyloid-\u03b2 and tau in Alzheimer\u2019s disease","volume":"23","author":"Busche","year":"2020","journal-title":"Nat. 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