This study examined how psilocybin works to reduce anxiety in mice by investigating the role of stress hormones, particularly corticosterone. Researchers found that psilocybin causes a temporary spike in corticosterone levels that is essential for its anxiety-reducing effects hours after administration. Interestingly, other interventions that increase corticosterone levels also produced similar anxiety-reducing effects, suggesting the stress hormone response itself drives the therapeutic benefit rather than psilocybin’s psychedelic properties alone. These findings suggest that measuring cortisol levels in human patients receiving psilocybin therapy could help explain and optimize therapeutic outcomes.