278 | DMT Pharmacokinetics and Brain Dynamics: Insights from Whole Brain Modeling

Theoretical and Computational Neuroscience

Author: Juan Ignacio Piccinini | Email: piccijuan@gmail.com

Juan Ignacio Piccinini , Yonatan Sanz Pearl , Enzo Tagliazucchi 1

1° Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Departamento de Física, Instituto de Física Interdisciplinaria y Aplicada (INFINA). Buenos Aires, Argentina.
2° Center for Brain and Cognition, Computational Neuroscience Group, Universitat Pompeu Fabra, Barcelona.

DMT, a powerful psychedelic, holds promise for therapeutic applications ranging from addressing mental health conditions to understanding consciousness itself. However, uncovering the precise mechanisms underlying DMT’s effects on the human brain remains a complex challenge. In this context, the utilization of Whole Brain models emerges as a valuable tool for dissecting the intricate mechanics of the brain. Whole Brain models provide a comprehensive framework that allows us to simulate and study the collective behavior of brain regions, enabling a bottom-up understanding of brain dynamics.

Using computational models that combine local dynamics with in vivo measurements of anatomical and dynamical functional connectivity of subjects under DMT and Placebo we were able to replicate the effects of the pharmacokinetics of the drug on the dynamic regime of the brain, showing that the onset of the drug results in a shift towards an increasingly unstable state, with oscillations exhibiting a complex envelope, followed by a gradual recovery of the baseline state as the effects of the drug wear off.

Furthermore, by introducing perturbations to different brain areas and observing ensuing effects under the influence of DMT and placebo, we characterize this transient unstable state in terms of its susceptibility to external stimuli, with implications to the understanding of large-scale information transfer during the psychedelic state.