Network control energy reductions under DMT relate to serotonin receptors, signal diversity, and subjective experience

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 ...

Full description

Saved in:
Bibliographic Details
Main Authors: S. Parker Singleton, Christopher Timmermann, Andrea I. Luppi, Emma Eckernäs, Leor Roseman, Robin L. Carhart-Harris, Amy Kuceyeski
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:Communications Biology
Online Access:https://doi.org/10.1038/s42003-025-08078-9
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850145150577147904
author S. Parker Singleton
Christopher Timmermann
Andrea I. Luppi
Emma Eckernäs
Leor Roseman
Robin L. Carhart-Harris
Amy Kuceyeski
author_facet S. Parker Singleton
Christopher Timmermann
Andrea I. Luppi
Emma Eckernäs
Leor Roseman
Robin L. Carhart-Harris
Amy Kuceyeski
author_sort S. Parker Singleton
collection DOAJ
description 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.
format Article
id doaj-art-da2ff8dbe9bd408fb80fd4577289501e
institution OA Journals
issn 2399-3642
language English
publishDate 2025-04-01
publisher Nature Portfolio
record_format Article
series Communications Biology
spelling doaj-art-da2ff8dbe9bd408fb80fd4577289501e2025-08-20T02:28:10ZengNature PortfolioCommunications Biology2399-36422025-04-018111310.1038/s42003-025-08078-9Network control energy reductions under DMT relate to serotonin receptors, signal diversity, and subjective experienceS. Parker Singleton0Christopher Timmermann1Andrea I. Luppi2Emma Eckernäs3Leor Roseman4Robin L. Carhart-Harris5Amy Kuceyeski6Department of Computational Biology, Cornell UniversityCenter for Psychedelic Research, Department of Brain Science, Imperial College LondonMontreal Neurological InstituteUnit for Pharmacokinetics and Drug Metabolism, Department of Pharmacology, Sahlgrenska Academy at University of GothenburgCenter for Psychedelic Research, Department of Brain Science, Imperial College LondonCenter for Psychedelic Research, Department of Brain Science, Imperial College LondonDepartment of Computational Biology, Cornell UniversityAbstract 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.https://doi.org/10.1038/s42003-025-08078-9
spellingShingle S. Parker Singleton
Christopher Timmermann
Andrea I. Luppi
Emma Eckernäs
Leor Roseman
Robin L. Carhart-Harris
Amy Kuceyeski
Network control energy reductions under DMT relate to serotonin receptors, signal diversity, and subjective experience
Communications Biology
title Network control energy reductions under DMT relate to serotonin receptors, signal diversity, and subjective experience
title_full Network control energy reductions under DMT relate to serotonin receptors, signal diversity, and subjective experience
title_fullStr Network control energy reductions under DMT relate to serotonin receptors, signal diversity, and subjective experience
title_full_unstemmed Network control energy reductions under DMT relate to serotonin receptors, signal diversity, and subjective experience
title_short Network control energy reductions under DMT relate to serotonin receptors, signal diversity, and subjective experience
title_sort network control energy reductions under dmt relate to serotonin receptors signal diversity and subjective experience
url https://doi.org/10.1038/s42003-025-08078-9
work_keys_str_mv AT sparkersingleton networkcontrolenergyreductionsunderdmtrelatetoserotoninreceptorssignaldiversityandsubjectiveexperience
AT christophertimmermann networkcontrolenergyreductionsunderdmtrelatetoserotoninreceptorssignaldiversityandsubjectiveexperience
AT andreailuppi networkcontrolenergyreductionsunderdmtrelatetoserotoninreceptorssignaldiversityandsubjectiveexperience
AT emmaeckernas networkcontrolenergyreductionsunderdmtrelatetoserotoninreceptorssignaldiversityandsubjectiveexperience
AT leorroseman networkcontrolenergyreductionsunderdmtrelatetoserotoninreceptorssignaldiversityandsubjectiveexperience
AT robinlcarhartharris networkcontrolenergyreductionsunderdmtrelatetoserotoninreceptorssignaldiversityandsubjectiveexperience
AT amykuceyeski networkcontrolenergyreductionsunderdmtrelatetoserotoninreceptorssignaldiversityandsubjectiveexperience