Psilocybin induces sex- and context-specific recruitment of the stress axis

ABSTRACT Psychedelics have reemerged as potential treatments for mental health disorders, yet their impact on stress-related brain regions remains poorly understood. Here, we provide the first real-time, in vivo evidence of psilocybin-induced neuronal activation, specifically in hypothalamic corticotropin-releasing hormone neurons. Notably, psilocybin elicited more pronounced responses in female mice and produced context-related alterations in threat assessment. Our findings provide valuable insight into the impact of psychedelics on a key stress center in the brain.