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
- Author: mycolabadmin
- 2/25/2025
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Summary
Researchers tested psilocin, the active ingredient in magic mushrooms, and found it could reduce seizures in mice at low doses (3-5 mg/kg) without causing psychedelic effects. The anticonvulsant benefits were mediated through several brain pathways including serotonin, cannabinoid, opioid, and nitric oxide signaling systems. The effects persisted for at least 9 days after a single dose, suggesting psilocin may have potential as a new treatment for epilepsy, though human clinical trials are needed to confirm these findings.
Background
Epilepsy affects approximately 65 million people globally, with 30-40% developing refractory epilepsy unresponsive to current medications. Psilocin, the active metabolite of psilocybin, has demonstrated antidepressant and anxiolytic properties in recent studies. This research investigates psilocin’s potential anticonvulsant effects through multiple neurobiological pathways.
Objective
To investigate the anticonvulsant efficacy of psilocin and elucidate the underlying mechanisms of action involving serotonergic, cannabinoid, opioidergic, nitrergic, and kynurenine pathways in mouse seizure models.
Results
Psilocin at 3-5 mg/kg demonstrated significant anticonvulsant effects in both PTZ and MES models, with effects persisting for at least 9 days post-administration. Co-administration of CB1 antagonist (AM-251), IDO inhibitor (1-MT), phosphodiesterase-5 inhibitor (sildenafil), and opioid antagonist (naltrexone) attenuated psilocin’s anticonvulsant effects. Western blotting revealed upregulation of 5-HT1A receptors and downregulation of IDO and CB1 expression following psilocin treatment.
Conclusion
Acute psilocin administration exhibits significant anticonvulsant properties mediated through modulation of 5-HT1A and CB1 receptors, the nitric oxide/cGMP pathway, and the kynurenine pathway via IDO. These findings suggest psilocin has therapeutic potential for epilepsy treatment, with anticonvulsant effects dissociated from psychoactive effects at low doses, though further clinical validation is required.
- Published in:Pharmacology Research & Perspectives,
- Study Type:Experimental Animal Study,
- Source: PMID: 39996441, DOI: 10.1002/prp2.70079