Single-dose DMT reverses anhedonia and cognitive deficits via restoration of neurogenesis in a stress-induced depression model.

ABSTRACT: Major depressive disorder (MDD) remains a leading cause of disability worldwide, with current treatments limited by delayed onset and low efficacy. The serotonergic psychedelic N,N-dimethyltryptamine (DMT) has shown rapid antidepressant effects in early clinical studies, yet its mechanisms and efficacy remain poorly characterized in established models of depression. Here, we evaluated the effects of a single dose of DMT (30 mg/kg, i.p.) in male mice exposed to the Chronic Unpredictable Mild Stress (UCMS) paradigm, a robust mouse model recapitulating key features of MDD, including anhedonia and cognitive impairment. DMT administered after UCMS reversed depressive-like behavior and restored cognitive performance, outperforming chronic fluoxetine across most domains. When administered during

SUBMITTER: Lima da Cruz RV 

PROVIDER: S-EPMC12923610 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature