A single dose of DMT reverses depression-like symptoms in mice by repairing brain circuitry

DMT shows antidepressant-like effects in a mouse model of chronic stress, with a single dose reversing depression-relevant behaviors. Mice exposed to 56 days of unpredictable mild stress were treated with DMT at 30 mg/kg either after the stress ended or during the protocol. DMT given after stress fully restored sugar-water preference (anhedonia readout) and improved performance on a radial arm maze task measuring cognitive function, while generally outperforming a 30-day fluoxetine condition across many tests. The study ties behavioral recovery to hippocampal circuitry repair: DMT increased dentate gyrus neurogenesis and reduced abnormal ectopic integration of newborn neurons. Benefits were also observed when DMT was administered under isoflurane anesthesia, suggesting a subjective psychedelic experience might not be strictly required, although effects were attenuated. Overall, the findings support a hypothesis that DMT reopens a brain plasticity window where timing and context determine whether stress-related symptoms translate into functional recovery.