Psilocybin reduces anxiety-like behavior in male mice four hours after treatment, an effect that depends on a temporary spike in the stress hormone corticosterone. Blocking the corticosterone rise or the glucocorticoid receptor eliminated the short-term anxiolytic effect. A nonpsychedelic drug that also raised corticosterone produced similar anxiety reduction, as did stress-induced hormone release alone. The anxiolytic effect lasted seven days after a single psilocybin dose, but this long-term benefit was lost in mice with chronically elevated corticosterone. The findings suggest that an acute, resolvable glucocorticoid surge is necessary for psilocybin's postacute anxiety relief, while chronic stress hormone elevation undermines its lasting effects.
Psilocybin, a serotonergic psychedelic, enhanced fear extinction and improved extinction recall 24 hours later in male mice, regardless of whether they were stress-naïve or had been exposed to acute or chronic stress beforehand. Psilocybin transiently increased the stress hormone corticosterone in stress-naïve mice but not in previously stressed animals. The findings suggest psilocybin can promote fear extinction across different stress backgrounds, supporting its potential therapeutic relevance for disorders like PTSD where prior stress is a key factor.