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Transient destabilization of whole brain dynamics induced by N,N-Dimethyltryptamine (DMT).

Juan Ignacio Piccinini, Yonatan Sanz Perl, Carla Pallavicini, Gustavo Deco, Morten L. Kringelbach, David Nutt, Robin Carhart-Harris, Christopher Timmermann, Enzo Tagliazucchi

Communications Biology March 11, 2025 DOI: 10.1038/s42003-025-07576-0 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Experimental study with computational modeling Peer reviewed
Sample size 15
Population Human volunteers under intravenous DMT
Interventions N N-Dimethyltryptamine (DMT)
Dose 20 mg intravenous
Topics DMT 5-MeO-DMT
Keywords Brain chemistry Consciousness research Psychedelics
Citations 6
Key findings A transient of heightened reactivity in fronto-parietal and visual regions correlates with serotonin 5HT2a receptor density, suggesting minimal perturbations can achieve maximal effects during the psychedelic state.

Abstract

The transition towards the brain state induced by psychedelic drugs is frequently neglected in favor of a static description of their acute effects. We use a time-dependent whole-brain model to reproduce large-scale brain dynamics measured with fMRI from 15 volunteers under 20 mg intravenous N,N-Dimethyltryptamine (DMT), a short-acting psychedelic. To capture its transient effects, we parametrize the proximity to a global bifurcation using a pharmacokinetic equation. Simulated perturbations reveal a transient of heightened reactivity concentrated in fronto-parietal regions and visual cortices, correlated with serotonin 5HT2a receptor density, the primary target of psychedelics. These advances suggest a mechanism to explain key features of the psychedelic state and also predicts that the temporal evolution of these features aligns with pharmacokinetics. Our results contribute to understanding how psychedelics introduce a transient where minimal perturbations can achieve a maximal effect, shedding light on how short psychedelic episodes may extend an overarching influence over time.

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