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

Summary

This study used computer models of brain activity to understand how the psychedelic drug DMT rapidly changes how the brain works during an acute experience. Researchers found that DMT pushes brain dynamics into a special state where the brain becomes hypersensitive to small changes or stimuli. This heightened sensitivity is strongest in brain regions rich in serotonin receptors and matches the expected timing of the drug’s effects, suggesting that brief psychedelic experiences may create lasting changes in the brain through this temporary destabilization window.

Background

Psychedelic drugs induce profound alterations in consciousness and brain dynamics, but most research focuses on steady-state effects rather than the dynamic transition to the psychedelic state. Previous whole-brain models have investigated static effects of psychedelics like LSD and psilocybin, but the temporal evolution of brain state changes during the acute psychedelic experience remains poorly understood.

Objective

To develop a time-dependent whole-brain model that captures the transient effects of intravenous DMT administration and explains how the drug destabilizes brain dynamics by bringing them closer to a global bifurcation point, correlating with drug pharmacokinetics and 5HT2a receptor density.

Results

DMT induced a rapid decrease in the bifurcation parameter with peak effects around 5 minutes, while placebo showed minimal temporal changes. DMT produced heightened reactivity to external perturbations concentrated in fronto-parietal and visual cortices, with peak differential reactivity strongly correlating with local 5HT2a receptor density (ρ = 0.91).

Conclusion

DMT transiently destabilizes whole-brain dynamics toward dynamic criticality, creating a window of heightened sensitivity to perturbations that aligns with known pharmacokinetics. This mechanism explains how brief psychedelic episodes can have prolonged effects and provides a computational framework for understanding the transition to altered states of consciousness.
  • Published in:Communications Biology,
  • Study Type:Computational Modeling Study with fMRI data,
  • Source: PMID: 40069397, DOI: 10.1038/s42003-025-07576-0
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