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Psilocin, the active metabolite of psilocybin, a well\u2010known psychedelic compound, has recently gained attention for its potential antidepressant and anxiolytic properties. This study aims to investigate the anticonvulsant effects of psilocin. The study utilizes behavioral seizure models and electrophysiological recordings in mice to assess the anticonvulsant efficacy of psilocin. The pentylenetetrazole (PTZ) test for clonic seizures and the maximal electroshock (<jats:styled-content style=\"fixed-case\">MES<\/jats:styled-content>) test for generalized tonic\u2013clonic seizures are employed. Cortical electrical activity is monitored to provide insights into the compound's effects on neuronal activity. The involvement of kynurenine pathway, opioidergic and nitrergic systems, as well as cannabinoid receptors using agonist\/antagonist paradigms. Western blotting was employed to evaluate the expression levels of key receptors and enzymes implicated in psilocin's anticonvulsant effects. The findings indicate a possible modulation of seizure activity by psilocin, with modest doses (3\u2009mg\/kg, i.p.) demonstrating potential anticonvulsant effects. Remarkably, the administration of 1\u2010<jats:styled-content style=\"fixed-case\">MT<\/jats:styled-content>, L\u2010<jats:styled-content style=\"fixed-case\">NAME<\/jats:styled-content>, naltrexone, sildenafil, and <jats:styled-content style=\"fixed-case\">AM<\/jats:styled-content>\u2010251 led to a diminishment of the anticonvulsant effects of psilocin, underscoring the involvement of the kynurenine pathway, nitrergic and opioidergic systems, <jats:styled-content style=\"fixed-case\">cGMP<\/jats:styled-content>, and the <jats:styled-content style=\"fixed-case\">CB1<\/jats:styled-content> receptor in mediating the anticonvulsant effects of psilocin, respectively. Based on western blotting analysis, the upregulation of 5\u2010<jats:styled-content style=\"fixed-case\">HT1A<\/jats:styled-content> but not 5\u2010<jats:styled-content style=\"fixed-case\">HT2A<\/jats:styled-content> and the downregulation of <jats:styled-content style=\"fixed-case\">IDO<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">CB1<\/jats:styled-content> expression following psilocin administration were observed. Acute administration of psilocin exerts anticonvulsant effects that might be mediated at least in part through the kynurenine pathway, opioidergic, serotonergic, and nitrergic systems.<\/jats:p>","DOI":"10.1002\/prp2.70079","type":"journal-article","created":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T07:14:02Z","timestamp":1741590842000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Psilocin, A Psychedelic Drug, Exerts Anticonvulsant Effects Against PTZ\u2010 and MES\u2010Induced Seizures in Mice via 5\u2010HT1A and CB1 Receptors: Involvement of Nitrergic, Opioidergic, and Kynurenine Pathways"],"prefix":"10.1002","volume":"13","author":[{"given":"Mohammad","family":"Balabandian","sequence":"first","affiliation":[{"name":"Experimental Medicine Research Center Tehran University of Medical Sciences  Tehran Iran"},{"name":"School of Medicine Iran University of Medical Sciences  Tehran 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