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Cited by 177Psychedelics and Drug StudiesNeurotransmitter Receptor Influence on BehaviorHallucinations in medical conditions

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N, N-Dimethyltryptamine (DMT), an Endogenous Hallucinogen: Past, Present, and Future Research to Determine Its Role and Function

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Barker, Steven A.·2018·Frontiers in Neuroscience
DOI 10.3389/fnins.2018.00536PMC PMC6088236
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Abstract

This report provides a historical overview of research concerning the endogenous hallucinogen N, N-dimethyltryptamine (DMT), focusing on data regarding its biosynthesis and metabolism in the brain and peripheral tissues, methods and results for DMT detection in body fluids and brain, new sites of action for DMT, and new data regarding its possible physiological and therapeutic roles. Research that further elaborates its consideration as a putative neurotransmitter is also addressed. Taking these studies together, the report proposes several new directions and experiments to ascertain the role of DMT in the brain, including brain mapping of enzymes responsible for the biosynthesis of DMT, further studies to elaborate its presence and role in the pineal gland, a reconsideration of binding site data, and new administration and imaging studies. The need to resolve the "natural" role of an endogenous hallucinogen from the effects observed from peripheral administration are also emphasized.

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Crossref · 10.3389/fnins.2018.00536

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Figures

Figure 1 Structure of N, N-dimethyltryptamine (DMT, 1).
Figure 1 Structure of N, N-dimethyltryptamine (DMT, 1).CC BY · PubMed Central
Figure 2 Pathways for the biosynthesis and metabolism of DMT, 1. Biosynthesis: Tryptophan (2) is converted to tryptamine (TA, 3) by aromatic amino acid decarboxylase (AADC). TA is dimethylated to first yield N-methyltryptamine (NMT, 4) and then DMT (1) by indole-N-methyltransferase (INMT), using S-adenosyl-methionine (SAM) as the methyl source. Metabolism: TA, NMT and DMT are all substrates for monoamine oxidase, yielding indole-3-acetic acid (5, IAA) as both a common precursor metabolite and the most abundant metabolite of DMT itself. DMT is also converted to DMT-N-oxide (6) as the second-most abundant metabolite. Two 1,2,3,4-tetrahydro-beta-carbolines (THBCs) have also been identified as metabolites; 2-methyl-THBC (7, MTHBC) and THBC (8).
Figure 2 Pathways for the biosynthesis and metabolism of DMT, 1. Biosynthesis: Tryptophan (2) is converted to tryptamine (TA, 3) by aromatic amino acid decarboxylase (AADC). TA is dimethylated to first yield N-methyltryptamine (NMT, 4) and then DMT (1) by indole-N-methyltransferase (INMT), using S-adenosyl-methionine (SAM) as the methyl source. Metabolism: TA, NMT and DMT are all substrates for monoamine oxidase, yielding indole-3-acetic acid (5, IAA) as both a common precursor metabolite and the most abundant metabolite of DMT itself. DMT is also converted to DMT-N-oxide (6) as the second-most abundant metabolite. Two 1,2,3,4-tetrahydro-beta-carbolines (THBCs) have also been identified as metabolites; 2-methyl-THBC (7, MTHBC) and THBC (8).CC BY · PubMed Central
Figure 3 Structure of α, α, β, β-teradeutero-DMT (9). D = deuterium.
Figure 3 Structure of α, α, β, β-teradeutero-DMT (9). D = deuterium.CC BY · PubMed Central

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Citations

Cites

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Research works printed but not linked: 7

  1. Cozzi, 2011, Indolethylamine-N-methyltransferase expression in primate nervous tissue, Abstr. Soc. Neurosci., 37, 840
  2. Goncalves de Lima, 1946, Observacio es sobre o “vinho de Jurema” utilizado pelos indios Pancaru' de Tacaratu' (Pernambuco) [Observations on the “vinho de Jurema” used by the Pancaru' Indians of Tacaratu' (Pernambuco)], Ariquivos do Instituto de Pesquisas Agronomicas, 4, 45
  3. Lu, 1974, Correlation between brain N,N-dimethyltryptamine (DMT) levels and bar pressing behavior in rats: effect of MAO inhibition, Pharmacologist, 16, 237
  4. McKenna, 1998, The scientific investigation of ayahuasca: a review of past and current research, Heffter Rev. Psychedelic Res., 1, 65
  5. Mishor, 2011, Chapter 5: DMT and Human Consciousness, 85
  6. Shulgin, 1997, Tihkal: The Continuation
  7. Szára, 1961, Hallucinogenic effects and metabolism of tryptamine derivatives in man, Fed. Proc., 20, 885

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Metadata

Authors
Barker, S. A.
Affiliations
Louisiana State University (US)
Corresponding author
Barker, Steven A.
ORCID
Barker, Steven A.
Venue
Frontiers in Neuroscience
Publisher
Frontiers Media SA
Published
2018-08-06
Volume
12
Pages
536-536
ISSN
1662-453X (ISSN-L)
DOI
10.3389/fnins.2018.00536
PMC
PMC6088236
OpenAlex
W2885412565
Cited by
177
References
135
Citations by year
2026: 14 · 2025: 29 · 2024: 29 · 2023: 38 · 2022: 26 · 2021: 16 · 2020: 16 · 2019: 7 · 2018: 1
FWCI
1.68
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Neuroscience (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Topics
  • Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Hallucinations in medical conditions
Keywords
N,N-dimethyltryptamine, DMT, pineal gland

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