Endogenous hallucinogens as ligands of the trace amine receptors: a possible role in sensory perception.
Abstract
While the endogenous hallucinogens, N,N-dimethyltryptamine, 5-hydroxy-N,N-dimethyl-tryptamine and 5-methoxy-N,N-dimethyltryptamine, have been acknowledged as naturally occurring components of the mammalian body for decades, their biological function remains as elusive now as it was at the time of their discovery. The recent discovery of the trace amine associated receptors and the activity of DMT and other hallucinogenic compounds at these receptor sites leads to the hypothesis that the endogenous hallucinogens act as neurotransmitters of a subclass of these trace amine receptors. Additionally, while activity at the serotonin 5-HT2A receptor has been proposed as being responsible for the hallucinogenic affects of administered hallucinogens, in their natural setting the 5-HT2A receptor may not interact with the endogenous hallucinogens at all. Additionally 5-HT2A agonist activity is unable to account for the visual altering effects of many of the administered hallucinogens; these effects may be mediated by one of the endogenous hallucinogen trace amine receptors rather than the serotonin 5-HT2A receptor. Therefore, activity at the trace amine receptors, in addition to serotonin receptors, may play a large role in the sensory altering effects of administered hallucinogens and the trace amine receptors along with their endogenous hallucinogen ligands may serve an endogenous role in mediating sensory perception in the mammalian central nervous system. Thus the theory proposed states that these compounds act as true endogenous hallucinogenic transmitters acting in regions of the central nervous system involved in sensory perception.
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DMT is present in mammalian organisms, including human blood, brain, and cerebrospinal fluid, and in the rat pineal gland.
“The hallucinogenic component DMT is abundant in the plant kingdom (Khan et al., 2012) and it is also present in mammalian organism; studies have detected it in human blood, brain, cerebrospinal fluid (Wallach, 2009), and the pineal gland of rats (Barker et al., 2013).”
From The therapeutic potentials of Ayahuasca: possible effects against various diseases of civilization (2016) · cites this paper as Wallach, 2009
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- Authors
- Wallach, J. V.
- Corresponding author
- Wallach, J.V.
- ORCID
- Wallach, J.V.
- Venue
- Medical Hypotheses
- Publisher
- Elsevier BV
- Published
- 2009-01
- Volume
- 72
- Issue
- 1
- Pages
- 91-94
- ISSN
- 0306-9877 (ISSN-L)
- OpenAlex
- W2117219351
- Cited by
- 59
- References
- 32
- Citations by year
- 2025: 5 · 2024: 5 · 2023: 2 · 2022: 6 · 2021: 2 · 2020: 2 · 2019: 2 · 2018: 4 · 2017: 5 · 2016: 5 · 2015: 4 · 2014: 5 · 2013: 2 · 2012: 3
- FWCI
- 2.61
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Medical Hypotheses (publishedVersion)
- PubMed (publishedVersion)
- 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, 5-MeO-DMT, 5-HT2A receptor, sensory perception, hallucinogenic effects, neurotransmitters, visual perception
- MeSH terms
- Trace Amine-Associated Receptors, Animals, Hallucinogens, Humans, Ligands, Mammals, Nuclear Proteins, Sensation, Visual Perception, Receptors, Odorant, Neurotransmitter Agents, Cell Cycle Proteins, Receptors, G-Protein-Coupled
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