The Psychedelic Psilocin Suppresses Activity of Central Amygdala Corticotropin-Releasing Factor Receptor 1 Neurons and Decreases Ethanol Drinking in Female Mice
Journal of Neuroscience November 10, 2025 Sarah N. Magee, Allison C. Sereno, Maria Echeveste-Sanchez et al.
Psilocin, the active metabolite of psilocybin, acutely reduced voluntary ethanol consumption in mice exposed to two models of chronic ethanol exposure without altering locomotor behavior. It increased activation of the central amygdala (CeA) and decreased relative activation of corticotropin-releasing factor type 1 (CRF1) receptors in CeA subregions of ethanol-naive female mice, with similar effects observed in chronic ethanol-exposed mice at 24 and 72 hours of withdrawal. Psilocin also elevated corticosterone levels at 24 hours but not at 72 hours of withdrawal. These findings indicate that psilocin engages CeA circuitry and reduces relative CRF1 activation alongside acute reductions in drinking, helping explain potential therapeutic mechanisms for alcohol use disorder.