Psilocin, the active metabolite of psilocybin, shows anticonvulsant effects in mice at a modest dose of 3 mg/kg. Behavioral seizure models and electrophysiological recordings indicate that psilocin modulates seizure activity. The anticonvulsant effects were diminished by administration of 1-MT, L-NAME, naltrexone, sildenafil, and AM-251, implicating the kynurenine pathway, nitrergic and opioidergic systems, cGMP, and CB1 receptors. Western blotting revealed upregulation of 5-HT1A and downregulation of IDO and CB1 expression. Acute psilocin administration exerts anticonvulsant effects mediated at least partly through these systems.
Psilocin, the active metabolite of psilocybin, reduced scratching in mice by interfering with the kynurenine pathway and interacting with 5-HT2A receptors. In a study with eight mice per group, psilocin at 1 mg/kg produced the strongest antipruritic and hallucinogenic effects, as measured by head-twitch response. Combining psilocin with 1-MT further enhanced itch relief. Psilocin decreased expression of TLR-4, TNF-α, and indoleamine-2,3-dioxygenase (IDO) in skin tissue. This is the first evidence that psychedelics may combat itching, suggesting a potential new use for psilocin in conditions involving pruritus.