Researchers find DMT provides longer-lasting antidepressant effects than S-ketamine in animal models

N,N-dimethyltryptamine (DMT) produced rapid antidepressant-like and anxiolytic-like effects in mice that lasted longer than those from S-ketamine in the same learned helplessness model. In male Swiss mice, researchers induced learned helplessness with unpredictable foot shocks. A single injection of either saline, S-ketamine, or DMT was given, followed by behavioral testing across days. Both DMT and S-ketamine reversed escape-related despair at 24 hours in group-housed mice, and both prevented anhedonia, measured as maintained preference for sucrose water, for at least five days. Over time, S-ketamine effects on behavioral despair were shorter, while DMT continued to show despair-related benefit for up to eight days. In anxiety-like testing, DMT increased exploration of open arms in the elevated plus-maze after five days, whereas S-ketamine did not. The study also reports brief short-term sedation after dosing and notes limitations such as use of only male mice and missing head-twitch measurement for hallucination intensity.