Neuropharmacology of N,N-dimethyltryptamine

Carbonaro, Theresa M.; Gatch, Michael B.

doi:10.1016/j.brainresbull.2016.04.016

Cited by 268Psychedelics and Drug StudiesAlkaloids: synthesis and pharmacologyNeurotransmitter Receptor Influence on Behavior

Neuropharmacology of N,N-dimethyltryptamine

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Carbonaro, Theresa M., Gatch, Michael B.·2016·Brain Research Bulletin

DOI 10.1016/j.brainresbull.2016.04.016PMC PMC5048497

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Abstract

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.
“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]
Section 3.2 reports DMT binding to both 5-HT2A and sigma-1 receptors and discusses sigma-1-dependent plasticity changes. It does not say sigma-1 receptors are highly expressed in the hippocampus, and it describes DMT’s sigma-1 activity as requiring micromolar concentrations, in contrast to the nanomolar affinities of selective sigma-1 agonists. The claim of high sigma-1 affinity is therefore not supported. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Psychotria viridis contains DMT, a hallucinogenic tryptamine that acts as a 5-HT1A/2A/2C agonist.
“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]
The Introduction identifies Psychotria as a genus containing DMT and describes DMT’s hallucinogenic effects. Section 3.2.1 describes DMT as a partial agonist at 5-HT1A, 5-HT2A and 5-HT2C receptors. Our copy does not explicitly establish that the particular species Psychotria viridis contains DMT. (LLM, conf=0.85)
Experimental — accuracy not yet measured
Tryptamine derivatives function as neurotransmitters.
“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]
Section 1.2, “Endogenous roles of DMT” (page unavailable), says DMT may act as a neurotransmitter, but describes its biological role as unestablished. The claim presents neurotransmitter function as established for tryptamine derivatives generally, which this discussion of DMT does not support. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Tryptamine derivatives cross the blood-brain barrier by active transport via Mg2+ and ATP-dependent uptake.
“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]
Section 2.2, “Accumulation and storage,” says that DMT crosses the blood–brain barrier by active transport involving Mg2+- and ATP-dependent uptake. It does not establish that this mechanism applies to tryptamine derivatives generally. Section 2.1 describes tryptamine as a precursor to DMT, but does not characterize tryptamine derivatives as neurotransmitter precursors. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Dimethyltryptamine and other tryptamine derivatives cross the blood-brain barrier by active transport across the endothelial plasma membrane.
“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]
Section 2.2, “Accumulation and storage” (page not provided), states that DMT crosses the blood–brain barrier by active transport across the endothelial plasma membrane. It mentions other tryptamines as substrates for SERT and VMAT2, but does not say they cross the blood–brain barrier by that mechanism. (LLM, conf=0.88)
Experimental — accuracy not yet measured

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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.
ORCID: Carbonaro, Theresa M.
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)
DOI: 10.1016/j.brainresbull.2016.04.016
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 · 2012: 1
FWCI: 1.58
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
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

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Neuropharmacology of N,N-dimethyltryptamine

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