Transient destabilization of whole brain dynamics induced by N,N-Dimethyltryptamine (DMT)
Using a time-dependent whole-brain model parametrised by DMT pharmacokinetics, the authors show that intravenous DMT transiently moves the brain toward a global bifurcation, producing a brief increase in network reactivity concentrated in fronto‑parietal and visual cortices that correlates with 5‑HT2A receptor density. This provides a mechanistic account of the psychedelic state and predicts that its temporal evolution tracks DMT pharmacokinetics.
Authors
- Enzo Tagliazucchi
- Robin Carhart-Harris
- David Nutt
Published
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.
Research Summary of 'Transient destabilization of whole brain dynamics induced by N,N-Dimethyltryptamine (DMT)'
Introduction
Psychedelic drugs modulate brain activity across molecular, cellular and large-scale network levels, yet most neuroimaging work has characterised their effects as static ‘‘steady states’’ rather than as transient processes. Previous computational whole-brain models have reproduced steady-state signatures of classic psychedelics (for example, increased entropy and expanded repertoire of brain states) and have implicated modulation of 5HT2A receptor-mediated synaptic gain. However, it remains unclear whether those mechanisms explain the rapid transitions into and out of altered states produced by fast-acting compounds, and whether the time course of network-level changes follows drug pharmacokinetics. Piccinini and colleagues set out to model the transient whole-brain dynamics induced by intravenous DMT, a short-acting psychedelic whose subjective effects peak and remit within tens of minutes. Their aim was to introduce time dependence into a whole-brain model by parametrising the bifurcation parameter (which governs proximity to a global dynamical critical point) with a simple pharmacokinetic-like gamma function, fit that model to fMRI-derived functional connectivity dynamics (FCD) from participants receiving 20 mg intravenous DMT versus placebo, and then use simulated perturbations to probe how reactivity varies over time and across regions in relation to 5HT2A receptor density. This approach tests whether DMT transiently shifts large-scale dynamics closer to a global bifurcation (dynamic criticality), thereby increasing sensitivity to perturbations, and whether the temporal profile of that shift aligns with the drug’s expected pharmacokinetics. The short duration of intravenous DMT makes it particularly suitable to distinguish time-dependent pharmacological effects from slower non-pharmacological processes such as expectation or mood changes.
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Study Details
- Study Typeindividual
- Journal
- Compound
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- APA Citation
Piccinini, J. I., Sanz Perl, Y., Pallavicini, C., Deco, G., Kringelbach, M., Nutt, D., Carhart-Harris, R., Timmermann, C., & Tagliazucchi, E. (2025). Transient destabilization of whole brain dynamics induced by N,N-Dimethyltryptamine (DMT). Communications Biology, 8(1). https://doi.org/10.1038/s42003-025-07576-0
References (38)
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Kwan, A. C., Olson, D. E., Preller, K. H. et al. · Nature Medicine (2022)
Zamberlan, F., Sanz, C., Pallavicini, C. et al. · Frontiers in Integrative Neuroscience (2018)
Carhart-Harris, R. L., Roseman, L., Haijen, E. C. H. M. et al. · Journal of Psychopharmacology (2018)
Tagliazucchi, E., Roseman, L., Kaelen, M. et al. · Current Biology (2016)
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Timmermann, C., Roseman, L., Haridas, S. et al. · PNAS (2023)
Preller, K. H., Burt, J. B., Adkinson, B. et al. · eLife (2018)
Luppi, A. I., Carhart-Harris, R. L., Roseman, L. et al. · NeuroImage (2021)
Bedford, P., Hauke, D. J., Wang, Z. et al. · Neuropsychopharmacology (2022)
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Show all 38 referencesShow fewer
Schartner, M., Carhart-Harris, R. L., Barrett, A. B. et al. · Scientific Reports (2017)
Viol, A., Palhano-Fontes, F., Onias, H. et al. · Scientific Reports (2017)
Timmermann, C., Roseman, L., Schartner, M. et al. · Scientific Reports (2019)
Lebedev, A. V., Kaelen, M., L€ Ovd En, M. et al. · Human Brain Mapping (2016)
Deco, G., Cruzat, J., Cabral, J. et al. · Current Biology (2018)
Kringelbach, M. L., Cruzat, J., Cabral, J. et al. · PNAS (2020)
Burt, J. B., Preller, K. H., Demirtaş, M. et al. · eLife (2021)
Carhart-Harris, R. L., Leech, R., Shanahan, M. et al. · Frontiers in Human Neuroscience (2014)
Girn, M., Rosas, F. E., Daws, R. E. et al. · Trends in Cognitive Sciences (2023)
Jobst, B. M., Atasoy, S., Ponce-Alvarez, A. et al. · NeuroImage (2021)
Singleton, S. P., Luppi, A. I., Carhart-Harris, R. L. et al. · Nature Communications (2022)
Doss, M. K., Považan, M., Rosenberg, M. D. et al. · Translational Psychiatry (2021)
Perry, C. M., Malina, M. · Psychopharmacology (2021)
Mediano, P. A. M., Rosas, F. E., Timmermann, C. et al. · ACS Chemical Neuroscience (2024)
Dolder, P. C., Schmid, Y., Steuer, A. E. et al. · Clinical Pharmacokinetics (2017)
Holze, F., Becker, A. M., Kolaczynska, K. E. et al. · Clinical Pharmacology and Therapeutics (2022)
Ort, A., Smallridge, J. W., Sarasso, S. et al. · iScience (2023)
Atasoy, S., Leor, R., Kaelen, M. et al. · Scientific Reports (2017)
Varley, T. F., Carhart-Harris, R., Roseman, L. et al. · NeuroImage (2020)
Kaelen, M., Barrett, F. S., Roseman, L. et al. · Psychopharmacology (2015)
Kaelen, M., Roseman, L., Kahan, J. et al. · European Neuropsychopharmacology (2016)
Roseman, L., Leech, R., Feilding, A. et al. · Frontiers in Human Neuroscience (2014)
Aday, J. S., Mitzkovitz, C. M., Bloesch, E. K. et al. · Neuroscience and Biobehavioral Reviews (2020)
Good, M., Joel, Z., Benway, T. et al. · European Journal of Pharmacology (2022)
Mueller, F., Lenz, C., Dolder, P. C. et al. · Translational Psychiatry (2017)
Schmidt, A., Müller, F., Lenz, C. et al. · Psychological Medicine (2017)
Carhart-Harris, R. L., Erritzoe, D., Williams, T. et al. · PNAS (2012)
Grimm, O., Kraehenmann, R., Preller, K. H. et al. · European Neuropsychopharmacology (2018)
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