Network control energy reductions under DMT relate to serotonin receptors, signal diversity, and subjective experience
This re-analysis (n=14) applies a receptor-informed network control theory framework to investigate the effects of DMT on the brain's control energy landscape. It reveals that DMT, like LSD and psilocybin, reduces global control energy, with these trajectories correlating with EEG signal diversity and subjective intensity ratings. Furthermore, the regional effects of DMT correlate with serotonin 2a receptor density, demonstrating a potential proof-of-concept for predicting pharmacological intervention effects on brain dynamics using control models.
Authors
- Robin Carhart-Harris
- Christopher Timmermann
- Leor Roseman
Published
Abstract
Psychedelics offer a profound window into the human brain through their robust effects on perception, subjective experience, and brain activity patterns. The serotonergic psychedelic N,N-dimethyltryptamine (DMT) induces a profoundly immersive altered state of consciousness lasting under 20 min, allowing the entire experience to be captured during a single functional magnetic resonance imaging (fMRI) scan. Using network control theory, we map energy trajectories of 14 individuals undergoing fMRI during DMT and placebo. We find that global control energy is reduced after DMT injection compared to placebo. Longitudinal trajectories of global control energy correlate with longitudinal trajectories of electroencephalography (EEG) signal diversity (a measure of entropy) and subjective drug intensity ratings. At the regional level, spatial patterns of DMT's effects on these metrics correlate with serotonin 2a receptor density from positron emission tomography (PET) data. Using receptor distribution and pharmacokinetic information, we recapitulate DMT's effects on global control energy trajectories, demonstrating control models can predict pharmacological effects on brain dynamics.
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Study Details
- Study Typeindividual
- Journal
- Compounds
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- APA Citation
Singleton, S. P., Timmermann, C., Luppi, A. I., Eckernäs, E., Roseman, L., Carhart-Harris, R. L., & Kuceyeski, A. (2025). Network control energy reductions under DMT relate to serotonin receptors, signal diversity, and subjective experience. Communications Biology, 8(1). https://doi.org/10.1038/s42003-025-08078-9
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