Psilocin, A Psychedelic Drug, Exerts Anticonvulsant Effects Against PTZ‐ and MES‐Induced Seizures in Mice via 5‐HT1A and CB1 Receptors: Involvement of Nitrergic, Opioidergic, and Kynurenine Pathways
Mohammad Balabandian, Mohammad Amin Manavi, Ali Lesani, Hamed Shafaroodi, Alireza Foroumadi, Arya Afrooghe, Ahmad-Reza Dehpour, Razieh Mohammad Jafari, Neda Heidari, Javad Mirnajafi‐zadeh
Pharmacology Research & Perspectives February 25, 2025 DOI: 10.1002/prp2.70079 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Mice |
| Intervention | Psilocin |
| Dose | 3 mg/kg i.p. |
| Topics | Psilocybin |
| Keywords | Epilepsy Pharmacology Opioidergic Anticonvulsant Drug Hallucinogen Tiagabine Kynurenine Cannabinoid receptor |
| Citations | 4 |
| Key findings | Acute psilocin administration exerts anticonvulsant effects in mice, mediated through the kynurenine pathway, opioidergic, serotonergic, and nitrergic systems. |
Abstract
ABSTRACT Epilepsy, a chronic neurological disorder affecting around 65 million people globally, is characterized by recurrent, unprovoked epileptic seizures. Psilocin, 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 clonic seizures 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.
Comparable studies
Other preclinical and animal studies on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice | 2021 | Observational cohort | |
| Harnessing psilocybin: antidepressant-like behavioral and synaptic actions of psilocybin are independent of 5-HT2R activation in mice Mice | 2021 | Experimental study | |
| Psychedelics reopen the social reward learning critical period Mice | 2023 | Experimental study in mice | |
| Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species. C57BL/6J mice | 2020 | Experimental study with dose-response experiments | |
| Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning Mice | 2013 | Experimental study |
Citations in the library
Cited by 3
- Pathway-selective signaling of serotonergic psychedelics at 5-HT receptors: Implications for psychoactivity, safety, and therapeutic potential European Neuropsychopharmacology April 10, 2026
- Psilocybin, From Ancestral Use to Therapeutic Potential: A Multidimensional Review of Its Pharmacological Basis and Current Perspectives Human Psychopharmacology: Clinical and Experimental September 1, 2026
- Psilocybin as serotonergic therapy in epilepsy: Narrative review of potentials and limitations. British Journal of Clinical Pharmacology July 21, 2026
Cites 22
- Psilocybin with psychological support for treatment-resistant depression: six-month follow-up. Psychopharmacology November 8, 2017
- Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels Neuropsychopharmacology January 26, 2019
- Long-term effects of psychedelic drugs: A systematic review Neuroscience & Biobehavioral Reviews March 16, 2020
- Serotonin toxicity of serotonergic psychedelics Psychopharmacology July 12, 2021
- Classic Psychedelic Coadministration with Lithium, but Not Lamotrigine, is Associated with Seizures: An Analysis of Online Psychedelic Experience Reports Pharmacopsychiatry August 4, 2021
and 17 more in the library