Scientists discover psychedelic drug 5-MeO-DMT induces a state of "paradoxical wake"

5-MeO-DMT can induce a paradoxical wake state in mice, where animals stay behaviorally awake and moving while their brains generate slow-wave activity typical of deep non-REM sleep. In experiments with 42 adult male mice, 5-MeO-DMT caused slow-wave EEG patterns and even neuronal OFF-periods to occur during wakeful behaviors like exploring, grooming, and running. Pupils were highly dilated at the same time, and theta rhythms linked to movement and environmental exploration were suppressed, suggesting a dissociation between physical arousal and normal wake-associated brain rhythms. The effects depended on serotonin receptor pathways, since blocking specific serotonin receptors eliminated 5-MeO-DMT-linked pupil dilation and theta suppression. The authors also report that the drug reduced the usual rebound of slow waves after sleep deprivation and produced delayed compensatory REM changes over 48 hours, raising the possibility that psychedelic-induced slow-wave states could relate to plasticity and learning processes relevant to mental health.