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Vigilance state dissociation induced by 5-MeO-DMT in mice.

Benjamin J. B. Bréant, José Prius Mengual, Alexander Andrews, Anna Hoerder-Suabedissen, Jasmin Patel, David M. Bannerman, Trevor Sharp, Vladyslav V. Vyazovskiy

Commun Biol January 5, 2026 DOI: 10.1038/s42003-025-09412-x via PubMed Central

Summary

AI-generated from the abstract

Psychedelics like 5-MeO-DMT induce a dissociated brain state that combines features of waking and sleep, rather than a purely psychological change. In freely moving adult male mice, chronic neocortical recordings and pupillometry showed that the drug produces prominent slow oscillations in the cortex and marked pupil dilation while animals remain awake and moving. REM sleep was initially suppressed but overcompensated in the following 48 hours. When given immediately after sleep deprivation, 5-MeO-DMT reduced the subsequent rebound of slow-wave activity. This dissociated state may underlie psychedelic effects such as dream-like hallucinations and reopening of critical periods for plasticity.

Study at a glance

Characteristics Observational cohort Peer reviewed
Population Adult male mice
Intervention 5-MeO-DMT
Dose a short-acting psychedelic 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT)
Duration 48 hours post-injection
Citations 1
Key finding 5-MeO-DMT induces a dissociated state in awake, moving mice characterized by cortical slow oscillations and pupil dilation, with initial REM sleep suppression followed by overcompensation and attenuation of sleep deprivation-induced slow-wave rebound.

Abstract

Psychedelics lead to profound changes in subjective experience and behaviour, which are typically conceptualised in psychological terms rather than corresponding to an altered brain state or a distinct state of vigilance. Here, we performed chronic electrophysiological recordings from the neocortex concomitant with pupillometry in freely moving adult male mice following an injection of a short-acting psychedelic 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT). We report an acute induction of a dissociated state, characterised by prominent slow oscillations in the cortex and marked pupil dilation in behaviourally awake, moving animals. REM sleep was initially markedly suppressed, but was overcompensated in the subsequent 48 hours, while administration of 5-MeO-DMT immediately after sleep deprivation attenuated the subsequent rebound of sleep slow-wave activity. We argue that the occurrence of a dissociated state combining features of waking and sleep may fundamentally underpin the known and hypothesised effects of psychedelics - from dream-like hallucinations to reopening of the critical period for plasticity.

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