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Peer-reviewed articleOpen access

N,N-dimethyltryptamine effects on connectome harmonics, subjective experience and comparative psychedelic experiences.

Vohryzek JiD, Luppi AIiD, Atasoy S, Deco GiD, Carhart-Harris RLiD, Timmermann CiD, Kringelbach MLiD

Neuropsychopharmacology : official publication of the American College of NeuropsychopharmacologySep 12, 2025License: open accessUnited Kingdom, Spain, Denmark, United States1 citationsDOI: 10.1038/s41386-025-02190-4

Abstract

Exploring the intricate relationship between brain's structure and function, and how this affects subjective experience is a fundamental pursuit in neuroscience. Psychedelic substances offer a unique insight into the influences of specific neurotransmitter systems on perception, cognition and consciousness. Specifically, their impact on brain function propagates across the structural connectome - a network of white matter pathways linking different regions. To comprehensively grasp the effects of psychedelic compounds on brain function, we used a theoretically rigorous framework known as connectome harmonic decomposition. This framework provides a robust method to characterize how brain function intricately depends on the organized network structure of the human connectome. We show that the connectome harmonic repertoire under N,N-dimethyltryptamine (DMT) is reshaped in line with other reported psychedelic compounds - psilocybin, lysergic acid diethylamide (LSD) and ketamine. Furthermore, we show that the repertoire entropy of connectome harmonics increases under DMT, as with those other psychedelics. Importantly, we demonstrate for the first time that measures of energy spectrum difference and repertoire entropy of connectome harmonics index the intensity of subjective experience of the participants in a time-resolved manner reflecting close coupling between connectome harmonics and subjective experience.

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PsilocybinKetamineLSDDMT

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