Pharmacology research & perspectivesFeb 25, 2025

Psilocin’s seizure-reducing effects in mice involve serotonin and cannabinoid receptors and several brain chemical systems

Psychedelic Science Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Apr 6, 2026

Abstract

at a modest dose of 3 mg/kg may modulate seizure activity in mice.

The study suggests that psilocin could have potential anticonvulsant effects.
Administration of certain antagonists diminished the anticonvulsant effects of psilocin, indicating involvement of specific biological pathways.
Upregulation of the 5-HT1A receptor and downregulation of IDO and CB1 expression were observed following psilocin administration.
Psilocin's effects on seizure activity may involve the kynurenine pathway, opioidergic, serotonergic, and nitrergic systems.

Simplified

Epilepsy, a chronic neurological disorder affecting around 65 million people globally, is characterized by recurrent, unprovoked epileptic seizures. , the active metabolite of psilocybin, a well-known 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 and the maximal electroshock (MES) test for generalized tonic-clonic 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 mg/kg, i.p.) demonstrating potential anticonvulsant effects. Remarkably, the administration of 1-MT, L-NAME, naltrexone, sildenafil, and AM-251 led to a diminishment of the anticonvulsant effects of psilocin, underscoring the involvement of the kynurenine pathway, nitrergic and opioidergic systems, cGMP, and the CB1 receptor in mediating the anticonvulsant effects of psilocin, respectively. Based on western blotting analysis, the upregulation of 5-HT1A but not 5-HT2A and the downregulation of IDO and CB1 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.

Key numbers

3 mg/kg

Increase in Clonic Seizure Threshold

administered at this dose showed notable anticonvulsant effects.

30 min

Reduction in Seizure Duration

analysis indicated decreased seizure activity duration.

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Psilocin’s seizure-reducing effects in mice involve serotonin and cannabinoid receptors and several brain chemical systems

Abstract

Key numbers

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