A single dose of the psychedelic DMT reversed depression-like behavior and restored cognitive performance in male mice exposed to chronic stress, outperforming chronic fluoxetine across most measures. When given during the stress period, DMT reduced anhedonia but did not rescue cognitive deficits, indicating domain-specific long-lasting effects. All DMT regimens increased the integration of adult-born granule cells and reduced abnormally integrated cells in the brain, suggesting structural circuit repair. The role of the psychedelic experience remains uncertain because isoflurane anesthesia may have confounded results.
A single dose of the psychedelic DMT reversed depression-like behaviors and cognitive impairments in mice exposed to chronic stress, outperforming the standard antidepressant fluoxetine. When given during stress, DMT prevented anhedonia but not cognitive deficits. DMT remained effective even under anesthesia, suggesting its therapeutic action does not require the psychedelic experience. All DMT regimens increased the integration of adult-born granule cells in the brain and reduced abnormal cell integration. The findings position DMT as a promising rapid-acting antidepressant that works through structural brain repair.