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Neuropharmacology of N,N-dimethyltryptamine
Open accessAbstract
N,N-Dimethyltryptamine (DMT) is an indole alkaloid widely found in plants and animals. It is best known for producing brief and intense psychedelic effects when ingested. Increasing evidence suggests that endogenous DMT plays important roles for a number of processes in the periphery and central nervous system, and may act as a neurotransmitter. This paper reviews the current literature of both the recreational use of DMT and its potential roles as an endogenous neurotransmitter. Pharmacokinetics, mechanisms of action in the periphery and central nervous system, clinical uses and adverse effects are also reviewed. DMT appears to have limited neurotoxicity and other adverse effects except for intense cardiovascular effects when administered intravenously in large doses. Because of its role in nervous system signaling, DMT may be a useful experimental tool in exploring how brain works, and may also be a useful clinical tool for treatment of anxiety and psychosis.
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“DMT exhibits, besides the 5-HT2AR, also high affinity for the S1R, which is highly expressed in the hippocampus and is a stimulator of synaptic plasticity (99–101).”
From Psychedelics and Neuroplasticity: A Systematic Review Unraveling the Biological Underpinnings of Psychedelics. (2021) · cites this paper as [100]
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“The latter plant contains DMT (9), a hallucinogenic tryptamine that acts as a 5-HT1A/2A/2C agonist [54,128].”
From Molecular and Functional Imaging Studies of Psychedelic Drug Action in Animals and Humans. (2021) · cites this paper as [54]
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“Tryptamine derivatives function as neurotransmitters.[15]”
From Lipid Nanoparticles Enhance mRNA Delivery to the Central Nervous System Upon Intrathecal Injection (2025) · cites this paper as [15]
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“Tryptamine derivatives are neurotransmitter precursors that cross the BBB by active transport via Mg2+ and ATP-dependent uptake38–40.”
From Blood–brain-barrier-crossing lipid nanoparticles for mRNA delivery to the central nervous system (2025) · cites this paper as [38]
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“For example, dimethyltryptamine and other tryptamine derivatives have been shown to cross the BBB by active transport across the endothelial plasma membrane (21).”
From Neurotransmitter-derived lipidoids (NT-lipidoids) for enhanced brain delivery through intravenous injection (2020) · cites this paper as [21]
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“DMT (9) also showed an interaction with moderate affinity at sigma receptors [54].”
From Molecular and Functional Imaging Studies of Psychedelic Drug Action in Animals and Humans. (2021) · cites this paper as [54]
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“The MAO-Is prevent the degradation of the N,N-dimethyltryptamine (DMT) contained in the Psychotria viridis leaves or other additional plants, thereby DMT becomes orally bioavailable (7–9).”
From Potential therapeutic effects of an ayahuasca-inspired N,N-DMT and harmine formulation: a controlled trial in healthy subjects (2024) · cites this paper as [9]
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“The chemical structure of NT1 is based on the NT dimethyltryptamine, which has been reported to cross the BBB by active transport across the endothelial plasma membrane (21).”
From Neurotransmitter-derived lipidoids (NT-lipidoids) for enhanced brain delivery through intravenous injection (2020) · cites this paper as [21]
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Palhano-Fontes, F., Barreto, D., Onias, H., Andrade, K. C., Novaes, M. M., Pessoa, J. A., Mota-Rolim, S. A., Osório, F. L., Sanches, R., dos Santos, R. G., et al. (2019) · Psychological Medicine · doi:10.1017/s0033291718001356 · Cited by 852
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Metadata
- Authors
- Carbonaro, T. M., & Gatch, M. B.
- Affiliations
- Johns Hopkins University (US)
- University of North Texas Health Science Center (US)
- Corresponding author
- Gatch, Michael B.
- Venue
- Brain Research Bulletin
- Publisher
- Elsevier BV
- Published
- 2016-09
- Volume
- 126
- Issue
- Pt 1
- Pages
- 74-88
- ISSN
- 0361-9230 (ISSN-L)
- PMC
- PMC5048497
- OpenAlex
- W2344956345
- Semantic Scholar
- 4e7595808935387bb23d1835159e3c823766e578
- Cited by
- 268
- References
- 215
- Citations by year
- 2026: 30 · 2025: 49 · 2024: 39 · 2023: 32 · 2022: 34 · 2021: 30 · 2020: 21 · 2019: 14 · 2018: 10 · 2017: 6 · 2016: 2
- FWCI
- 1.58
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Brain Research Bulletin (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Addiction Treatment Discovery Program of the National Institute
- Topics
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Alkaloids: synthesis and pharmacology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- N,N-dimethyltryptamine, DMT, indole alkaloids, endogenous neurotransmitters, psychedelic effects, pharmacokinetics, mechanism of action, neurotoxicity, cardiovascular effects, recreational drug use, anxiety treatment, psychosis treatment
- MeSH terms
- Animals, Brain, N,N-Dimethyltryptamine, Hallucinogens, Humans, Neuropharmacology, Mood Disorders
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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