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Review
. 2018 Aug 6:12:536.
doi: 10.3389/fnins.2018.00536. eCollection 2018.

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

Steven A Barker  1
Affiliations
Review

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

Steven A Barker. Front Neurosci. .

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.

Keywords: N; N-dimethyltryptamine; brain; hallucinogen; neurotransmitter; psychedelic.

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Figures

Figure 1
Figure 1
Structure of N, N-dimethyltryptamine (DMT, 1).
Figure 2
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 3
Figure 3
Structure of α, α, β, β-teradeutero-DMT (9). D = deuterium.
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