Exploring DMT: Endogenous role and therapeutic potential.
Jakub Schimmelpfennig, Kamila Jankowiak-Siuda
Neuropharmacology May 1, 2025 DOI: 10.1016/j.neuropharm.2025.110314 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | DMT Neuroplasticity |
| Keywords | Psychedelics DMT Entheogens Hallucinogens Neuroprotection brain protection Neural defense Neuroprotective agents Neuroplasticity neural plasticity Anti-inflammation Hypoxia Inmt |
| Citations | 47 |
| Key findings | DMT may act as an endogenous ligand for intracellular receptors and play roles in neuroplasticity, neurogenesis, mitochondrial homeostasis, immunomodulation, and protection against hypoxia and oxidative stress. |
Abstract
N,N-Dimethyltryptamine (DMT) is a naturally occurring amine and psychedelic compound, found in plants, animals, and humans. While initial studies reported only trace amounts of DMT in mammalian brains, recent findings have identified alternative methylation pathways and DMT levels comparable to classical neurotransmitters in rodent brains, calling for a re-evaluation of its biological role and exploration of this inconsistency. This study evaluated DMT's biosynthetic pathways, focusing on indolethylamine N-methyltransferase (INMT) and its isoforms, and possible regulatory mechanisms, including alternative routes of synthesis and how physiological conditions, such as stress and hypoxia influence DMT levels. This review considers the impact of endogenous regulatory factors on DMT synthesis and degradation, particularly under conditions affecting monoamine oxidase (MAO) efficiency and activity. We also examined DMT's potential roles in various physiological processes, including neuroplasticity and neurogenesis, mitochondrial homeostasis, immunomodulation, and protection against hypoxia and oxidative stress. DMT's lipophilic properties allow it to cross cell membranes and activate intracellular 5-HT2A receptors, contributing to its role in neuroplasticity. This suggests DMT may act as an endogenous ligand for intracellular receptors, highlighting its broader biological significance beyond traditional receptor pathways. The widespread evolutionary presence of DMT's biosynthetic pathways across diverse species suggests it may play essential roles in various developmental stages and cellular adaptation to environmental challenges, highlighting the neurobiological significance of DMT and its potential clinical applications. We propose further research to explore the role of endogenous DMT, particularly as a potential neurotransmitter.
Comparable studies
Other narrative reviews on 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 | |
| Pharmahuasca: Human Pharmacology of Oral DMT Plus Harmine Human self-experimenters | 1999 | Review | n = 8 |
| The psychedelic model of schizophrenia: the case of N,N- dimethyltryptamine | 1976 | Review |
Citations in the library
Cited by 24
- Novel Indole Derivatives as Serotonergic Psychedelic Agents for Treating Psychosis, Mental Illness, and CNS Disorders. ACS Medicinal Chemistry Letters June 12, 2025
- Extraction and Characterization of N,N-Dimethyltryptamine from Mimosa tenuiflora: A Multivariate Approach ACS Omega September 16, 2025
- Optimized Parenteral and Intranasal Formulations of Tryptamine Psychedelics for Rapid-Acting Antidepressant Therapy. ACS Medicinal Chemistry Letters June 12, 2025
- Reducing Cardiovascular Side Effects of DMT Using Beta-Blockers. ACS Medicinal Chemistry Letters May 8, 2025
- Direct anti-inflammatory actions of N,N -dimethyltryptamine on microglia are revealed by proteomic profiling and receptor pharmacology bioRxiv (Cold Spring Harbor Laboratory) August 11, 2026
and 19 more in the library
Cites 114
- 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
- The Hallucinogen N,N -Dimethyltryptamine (DMT) Is an Endogenous Sigma-1 Receptor Regulator Science February 13, 2009
- Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors Science February 16, 2023
- Psychedelics promote plasticity by directly binding to BDNF receptor TrkB Nature Neuroscience June 1, 2023
and 109 more in the library