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

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 intravenou...

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Bibliographic Details
Main Authors: Juan Ignacio Piccinini, Yonatan Sanz Perl, Carla Pallavicini, Gustavo Deco, Morten Kringelbach, David Nutt, Robin Carhart-Harris, Christopher Timmermann, Enzo Tagliazucchi
Format: Article
Language:English
Published: Nature Portfolio 2025-03-01
Series:Communications Biology
Online Access:https://doi.org/10.1038/s42003-025-07576-0
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Summary: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.
ISSN:2399-3642