Brain substates induced by DMT relate to sympathetic output and meaningfulness of the experience

This pre-print re-analysis of data from a single-blind study (n=14) used multimodal neuroimaging techniques (fMRI + EKG) to investigate brain activity and autonomic physiology during DMT (20mg) altered state of consciousness. Results reveal unique brain activity substates, with increased superior temporal lobe activity and hippocampal deactivation under DMT, correlating with auditory distortions and meaningfulness of the experience, respectively. Moreover, increased heart rate under DMT correlates with hippocampal and medial parietal deactivation, suggesting a potential link between sympathetic regulation and positive mental health outcomes following psychedelic administration.

Abstract of Brain substates induced by DMT relate to sympathetic output and meaningfulness of the experience

“N,N-Dimethyltryptamine (DMT) is a serotonergic psychedelic, known to rapidly induce short-lasting alterations in conscious experience, characterized by a profound and immersive sense of physical transcendence alongside rich and vivid auditory distortions and visual imagery. Multimodal neuroimaging data paired with dynamic analysis techniques offer a valuable approach for identifying unique signatures of brain activity – and linked autonomic physiology – naturally unfolding during the altered state of consciousness induced by DMT. We leveraged simultaneous fMRI and EKG data acquired in 14 healthy volunteers prior to, during, and after intravenous administration of DMT, and, separately, placebo. EKG data was used to derive continuous heart rate; fMRI data was preprocessed to derive individual dynamic activity matrices, reflecting the similarity of brain activity in time, and community detection algorithms were applied on these matrices to identify brain activity substates. We identified a brain substate occurring immediately after DMT injection, characterized by increased superior temporal lobe activity, and hippocampal and medial parietal deactivations under DMT. Superior temporal lobe hyperactivity correlated with the intensity of the auditory distortions, while hippocampus and medial parietal cortex hypoactivity correlated with scores of meaningfulness of the experience. During this first post-injection substate, increased heart rate under DMT correlated negatively with the meaningfulness of the experience and positively with hippocampus/medial parietal deactivation. These results suggest a chain of influence linking sympathetic regulation to hippocampal and medial parietal deactivations under DMT, which combined may contribute to positive mental health outcomes related to self-referential processing following psychedelic administration.”

Authors: Lorenzo Pasquini, Alexander J. Simon, Courtney L. Gallen, Hannes Kettner, Leor Roseman, Adam Gazzaley, Robin L. Carhart-Harris & Christopher Timmermann

Summary of Brain substates induced by DMT relate to sympathetic output and meaningfulness of the experience


Bodily self-awareness is thought to result from the integration of visceral and autonomic bodily functions into a distributed brain network supporting homeostasis, interoception, and emotions, and the narrative self is thought to rely on a large-scale brain system associated with self-referential processes. DMT is a serotonergic psychedelic that rapidly induces an intense altered state of consciousness characterized by deep and profound immersion. This state typically lasts several minutes and gradually attenuates as participants regain normal waking consciousness approximately 20 min following the injection. DMT can cause changes in autonomic and central nervous system physiology, such as increased sympathetic tone and altered heart rate, which normalize as the effects of the drug dissipate. Studies using resting-state functional magnetic resonance imaging (rsfMRI) have shown that DMT results in global hyperconnectivity, collapsed hierarchical organization, and reduced intra-network integrity, particularly among core regions of the DMN. Further, dynamic analysis methods can be used to identify distinguishable physiological substates occurring during an entire scan.

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Brain substates induced by DMT relate to sympathetic output and meaningfulness of the experience

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Pasquini, L., Simon, A., Gallen, C., Kettner, H., Roseman, L., Gazzaley, A., ... & Timmermann, C. (2024). Brain substates induced by DMT relate to sympathetic output and meaningfulness of the experience. bioRxiv, 2024-02.

Study details

Compounds studied

Topics studied
Healthy Subjects Neuroscience

Study characteristics
Original Re-analysis Placebo-Controlled Single-Blind Within-Subject Randomized Re-analysis Bio/Neuro

14 Humans


Institutes associated with this publication

Imperial College London
The Centre for Psychedelic Research studies the action (in the brain) and clinical use of psychedelics, with a focus on depression.

Compound Details

The psychedelics given at which dose and how many times

DMT 20 mg | 1x

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