The evolution of N, N-Dimethyltryptamine: from metabolic pathways to brain connectivity.
Swanti Gupta, Raj K Bhatnagar, Dinesh Gupta, K Maharaj Kumari, Amla Chopra
Psychopharmacology April 11, 2025 DOI: 10.1007/s00213-025-06777-z (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Intervention | DMT |
| Topics | 5-MeO-DMT DMT |
| Keywords | Cognition Endogenous DMT Exogenous DMT Global neural network Psychedelics Consciousness Brain connectivity Neurotransmitters |
| Citations | 27 |
| Key findings | DMT enhances global functional connectivity in transmodal association cortices and alters brain wave dynamics, correlating with ego dissolution and its psychedelic effects. |
Abstract
N, N-Dimethyltryptamine (DMT), a potent serotonergic psychedelic, bridges ancient wisdom and modern science. The mechanisms underlying its powerful psychedelic effects and out-of-body experiences continue to intrigue scientists. The functional role of DMT remains ambiguous. This paper explores the endogenous presence of DMT in the human body and its diverse neuroregulatory functions, which influence hierarchical brain connectivity, and the mechanisms driving its psychedelic effects. This paper aims to analyze DMT-receptor binding, its effects on neuronal modulation, brain oscillations, and connectivity, and its influence on hallucinations, out-of-body experiences, and cognitive functions. DMT administration induces significant changes in brain wave dynamics, including reduced alpha power, increased delta power, and heightened Lempel-Ziv complexity, reflecting enhanced neural signal diversity. Functional neuroimaging studies reveal that DMT enhances global functional connectivity (GFC), particularly in transmodal association cortices such as the salience network, frontoparietal network, and default mode network, correlating with ego dissolution. The receptor density-dependent effects of DMT were mapped to brain regions rich in serotonin 5-HT2A receptors, supporting its role in modulating consciousness and neuroplasticity. This integrated analysis provides insights into the profound effects of DMT on human cognition, and consciousness, and its role in enhancing natural well-being. As we uncover the endogenous functions of DMT, it becomes clear that the study of its biology reveals a complex interplay between brain chemistry and consciousness.
Comparable studies
Other narrative reviews on 5-MeO-DMT, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Neuropharmacology of N,N-dimethyltryptamine | 2016 | Review | |
| N, N-Dimethyltryptamine (DMT), an Endogenous Hallucinogen: Past, Present, and Future Research to Determine Its Role and Function Humans and animals (general) | 2018 | Review | |
| Psychedelic 5-methoxy-N,N-dimethyltryptamine: metabolism, pharmacokinetics, drug interactions, and pharmacological actions. Humans (pharmacokinetics) | 2010 | Review | |
| Dark Classics in Chemical Neuroscience:N,N-Dimethyltryptamine (DMT) | 2018 | Review | |
| A possibly sigma-1 receptor mediated role of dimethyltryptamine in tissue protection, regeneration, and immunity. | 2013 | Review |
Citations in the library
Cited by 13
- Novel Indole Derivatives as Serotonergic Psychedelic Agents for Treating Psychosis, Mental Illness, and CNS Disorders. ACS Medicinal Chemistry Letters June 12, 2025
- Novel 6,5-Bicyclic Compounds as 5-HT2A Receptor Agonists for Treating Depression, Anxiety, Substance Abuse, and Headaches ACS Medicinal Chemistry Letters July 3, 2026
- Short- and Long-Acting Psychedelics: Structure-Activity Relationships, Pharmacology, and Implications for Neuropsychiatric Therapeutics. ACS Chemical Neuroscience June 17, 2026
- Novel 5,6-Bicyclic Compounds as 5-HT2A Receptor Agonists for Treating Depression, Anxiety, Substance Abuse, and Headaches ACS Medicinal Chemistry Letters June 3, 2026
- Novel Indoline Derivatives Serotonergic Psychedelic Agents as 5‑HT2A Agonists for Treating Psychosis, Mental Illness and CNS Disorders. ACS Medicinal Chemistry Letters April 27, 2026
and 8 more in the library
Cites 80
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- Neural correlates of the LSD experience revealed by multimodal neuroimaging. Proceedings of the National Academy of Sciences April 11, 2016
- Amphetamine, 3,4-Methylenedioxymethamphetamine, Lysergic Acid Diethylamide, and Metabolites of the Catecholamine Neurotransmitters Are Agonists of a Rat Trace Amine Receptor Molecular Pharmacology December 1, 2001
- Increased Global Functional Connectivity Correlates with LSD-Induced Ego Dissolution. Current Biology April 13, 2016
- The Hallucinogen N,N -Dimethyltryptamine (DMT) Is an Endogenous Sigma-1 Receptor Regulator Science February 13, 2009
and 75 more in the library