Psilocin, the Psychoactive Metabolite of Psilocybin, Modulates Select Neuroimmune Functions of Microglial Cells in a 5-HT₂ Receptor-Dependent Manner
department or school: Science, Irving K. Barber Faculty of (Okanagan)
department or school: Biology, Department of (Okanagan)
data provider: DSpace
identifier citation: Molecules 29 (21): 5084 (2024)
creator: Wiens, Kennedy R.
creator: Brooks, Noah A. H.
creator: Riar, Ishvin
creator: Greuel, Bridget K.
creator: Klegeris, Andis
creator: Lindhout, Ivan
issued: 2024-11-22T21:17:32Z
issued: 2024-10-28
description: 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–brain barrier and exerts psychotropic activity by interacting with the 5-hydroxytryptamine 2A receptors (5-HT₂ARs) on neurons. Since microglia express all three 5-HT₂AR 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.
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/89708
note: Citation: Wiens, K.R.; Brooks, N.A.H.;Riar, I.; Greuel, B.K.; Lindhout, I.A.;Klegeris, A. Psilocin, the PsychoactiveMetabolite of Psilocybin, ModulatesSelect Neuroimmune Functions ofMicroglial Cells in a 5-HT2Receptor-Dependent Manner.Molecules 2024, 29, 5084. https://doi.org/10.3390/molecules29215084Academic Editor: JoséMarco-ContellesReceived: 29 August 2024Revised: 16 October 2024Accepted: 17 October 2024Published: 28 October 2024Copyright: © 2024 by the authors.Licensee MDPI, Basel, Switzerland.This article is an open access articledistributed under the terms andconditions of the Creative CommonsAttribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).moleculesArticlePsilocin, the Psychoactive Metabolite of Psilocybin, ModulatesSelect Neuroimmune Functions of Microglial Cells in a 5-HT2Receptor-Dependent MannerKennedy R. Wiens, Noah A. H. Brooks, Ishvin Riar, Bridget K. Greuel , Ivan A. Lindhout and Andis Klegeris *Laboratory of Cellular and Molecular Pharmacology, Department of Biology, University of British ColumbiaOkanagan Campus, Kelowna, BC V1V 1V7, Canada* Correspondence: andis.klegeris@ubc.caAbstract: Neuroinflammation that is caused by microglia, the main immune cells of the brain,contributes to neurodegenerative diseases. Psychedelics, including psilocybin and lysergic acid di-ethylamide (LSD), possess certain anti-inflammatory properties and, therefore, should be consideredas drug candidates for treating neuroinflammatory pathologies. When ingested, psilocybin is rapidlydephosphorylated to yield psilocin, which crosses the blood–brain barrier and exerts psychotropicactivity by interacting with the 5-hydroxytryptamine 2A receptors (5-HT2ARs) on neurons. Sincemicroglia 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-likecell lines to demonstrate that psilocin, at non-toxic concentrations, did not affe…
has type: Article
is shown at: 10.14288/1.0447322
language: eng
peer review status: Reviewed
provider: Vancouver : University of British Columbia Library
publisher: Multidisciplinary Digital Publishing Institute
publisher DOI: 10.3390/molecules29215084
rights: CC BY 4.0
rights URI: https://creativecommons.org/licenses/by/4.0/
scholar level: Faculty
scholar level: Researcher
subject: affective disorders
subject: depression
subject: 5-hydroxytryptamine
subject: neurodegenerative diseases
subject: neuroprotection
subject: phagocytic activity
subject: reactive oxygen species
subject: reactive nitrogen species
subject: serotonin
type: Text
identifier URI: http://hdl.handle.net/2429/89708