Transient destabilization of whole brain dynamics induced by N,N-Dimethyltryptamine (DMT)
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.
Authors
- Carla Pallavicini (ORCID: https://orcid.org/0000-0001-9589-7735)
- Juan Piccinini
- David Nutt (ORCID: https://orcid.org/0000-0002-1286-1401)
- Robin Lester Carhart-Harris (ORCID: https://orcid.org/0000-0002-6062-7150)
- Morten L. Kringelbach (ORCID: https://orcid.org/0000-0002-3908-6898)
- Gustavo Deco (ORCID: https://orcid.org/0000-0002-8995-7583)
- Christopher Timmermann (ORCID: https://orcid.org/0000-0002-2281-377X)
- Enzo Tagliazucchi (ORCID: https://orcid.org/0000-0003-0421-9993)
- Yonatan Sanz Perl (ORCID: https://orcid.org/0000-0002-1270-5564)
Institutions
- Institució Catalana de Recerca i Estudis Avançats (ES)
- Centre National de la Recherche Scientifique (FR)
- Consejo Nacional de Investigaciones Científicas y Técnicas (AR)
- Universitat Pompeu Fabra (ES)
- University of California, San Francisco (US)
- Aarhus University (DK)
- Université Paris Cité (FR)
- Adolfo Ibáñez University (CL)
- Universidad de Buenos Aires (AR)
- University of Oxford (GB)
- Royal Academy of Music (DK)
- Centre de recherche cerveau et cognition (FR)
- Imperial College London (GB)
- Fundación Ciencias Exactas y Naturales (AR)
Publication Details
- Journal
- Communications Biology
- Published
- 2025-03-11
- DOI
- https://doi.org/10.1038/s42003-025-07576-0
- Citations
- 5
- Primary Topic
- Psychedelics and Drug Studies
- Type
- article
- Field-Weighted Citation Impact
- 11.53
Funders
- Consejo Nacional de Investigaciones Científicas y Técnicas
- Agencia Nacional de Investigación y Desarrollo