Human brain effects of DMT assessed via EEG-fMRI

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 120; no. 13; p. e2218949120
• Main Authors: Timmermann, Christopher, Roseman, Leor, Haridas, Sharad, Rosas, Fernando E., Luan, Lisa, Kettner, Hannes, Martell, Jonny, Erritzoe, David, Tagliazucchi, Enzo, Pallavicini, Carla, Girn, Manesh, Alamia, Andrea, Leech, Robert, Nutt, David J., Carhart-Harris, Robin L.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 28.03.2023
• Subjects: Agonists; Biological Sciences; Brain; Brain mapping; Cognitive science; Compression; Disintegration; EEG; Electroencephalography; Emission analysis; Functional magnetic resonance imaging; Hallucinogens - pharmacology; Humans; Magnetic Resonance Imaging; Medical imaging; N,N-Dimethyltryptamine - pharmacology; Neural networks; Neuroimaging; Placebos; Positron emission; Positron emission tomography; Psychedelic drugs; Receptors; Serotonin; Serotonin S2 receptors; psychedelics; ayahuasca; serotonin; consciousness; dimethyltryptamine
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.2218949120

Psychedelics have attracted medical interest, but their effects on human brain function are incompletely understood. In a comprehensive, within-subjects, placebo-controlled design, we acquired multimodal neuroimaging [i.e., EEG-fMRI (electroencephalography-functional MRI)] data to assess the effects of intravenous (IV) N,N-Dimethyltryptamine (DMT) on brain function in 20 healthy volunteers. Simultaneous EEG-fMRI was acquired prior to, during, and after a bolus IV administration of 20 mg DMT, and, separately, placebo. At dosages consistent with the present study, DMT, a serotonin 2A receptor (5-HT2AR) agonist, induces a deeply immersive and radically altered state of consciousness. DMT is thus a useful research tool for probing the neural correlates of conscious experience. Here, fMRI results revealed robust increases in global functional connectivity (GFC), network disintegration and desegregation, and a compression of the principal cortical gradient under DMT. GFC × subjective intensity maps correlated with independent positron emission tomography (PET)-derived 5-HT2AR maps, and both overlapped with meta-analytical data implying human-specific psychological functions. Changes in major EEG-measured neurophysiological properties correlated with specific changes in various fMRI metrics, enriching our understanding of the neural basis of DMT’s effects. The present findings advance on previous work by confirming a predominant action of DMT—and likely other 5-HT2AR agonist psychedelics—on the brain’s transmodal association pole, i.e., the neurodevelopmentally and evolutionarily recent cortex that is associated with species-specific psychological advancements, and high expression of 5-HT2A receptors.