Human brain effects of DMT assessed via EEG-fMRI.
Christopher Timmermann, Leor Roseman, Sharad Haridas, Fernando E. Rosas, Lisa Luan, Hannes Kettner, Jonny Martell, David Erritzøe, Enzo Tagliazucchi, Carla Pallavicini, Manesh Girn, Andrea Alamia, Robert Leech, David Nutt, Robin Carhart-Harris
Proceedings of the National Academy of Sciences March 28, 2023 DOI: 10.1073/pnas.2218949120 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Within-subjects, placebo-controlled design Peer reviewed |
|---|---|
| Sample size | 20 |
| Population | Healthy volunteers |
| Interventions | N N-Dimethyltryptamine (DMT) |
| Dose | 20 mg |
| Topics | Ayahuasca DMT Serotonin |
| Keywords | Psychedelics hallucinogens Entheogens Psychoactive drugs Neuroscience brain science Neural studies Neurobiology Consciousness awareness Cognition Mental states DMT Dimethylt |
| Citations | 217 |
| Key points | DMT robustly increases global functional connectivity, disintegrates and desegregates brain networks, and compresses the principal cortical gradient, predominantly affecting the transmodal association cortex. |
Abstract
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.
In the evidence
This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.
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State of the evidence: DMT Supports
A 20 mg IV bolus of DMT robustly increased global functional connectivity, disintegrated and desegregated brain networks, and compressed the principal cortical gradient, predominantly affecting transmodal association cortex.
Synthesized
Comparable studies
Other randomized controlled trials on DMT, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Dose-Response Study of N,N-Dimethyltryptamine in Humans Experienced hallucinogen users | 1994 | Double-blind, saline placebo-controlled, randomized study | n = 12 |
| DMT Models the Near-Death Experience Healthy participants | 2018 | Within-subjects placebo-controlled study | n = 13 |
| Psychological Effects of (S)-Ketamine and N,N-Dimethyltryptamine (DMT): A Double-Blind, Cross-Over Study in Healthy Volunteers Healthy volunteers | 2005 | Double-blind crossover study | n = 9 |
| Differential tolerance to biological and subjective effects of four closely spaced doses of N,N-dimethyltryptamine in humans Experienced hallucinogen users | 1996 | Randomized controlled trial | n = 13 |
| DMT alters cortical travelling waves. Participants receiving DMT and placebo (saline) with eyes closed | 2020 | Placebo-controlled crossover trial |
Citations in the library
Cited by 160
- A complex systems perspective on psychedelic brain action. Trends in Cognitive Sciences February 3, 2023
- In vivo mapping of pharmacologically induced functional reorganization onto the human brain’s neurotransmitter landscape Science Advances June 14, 2023
- Serotonin 2A Receptor (5-HT2AR) Agonists: Psychedelics and Non-Hallucinogenic Analogues as Emerging Antidepressants Chemical Reviews November 30, 2023
- A synergistic workspace for human consciousness revealed by Integrated Information Decomposition. Elife July 18, 2024
- Exploring DMT: Endogenous role and therapeutic potential. Neuropharmacology May 1, 2025
and 155 more in the library
Cites 50
- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
- The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs Frontiers in Human Neuroscience 2014
- Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin Proceedings of the National Academy of Sciences January 23, 2012
- REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics Pharmacological Reviews June 20, 2019
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
and 45 more in the library