Significance of mammalian N, N-dimethyltryptamine (DMT): A 60-year-old debate
This review (2022) explores the role of endogenously (within the animal) produced DMT in mammalian physiology by exploring 60 years of research. The biosynthesis of DMT, its receptor activity, and regulation are discussed while key experiments are used to prove what role DMT plays in the body such as a neurotransmitter and/or a hormone.
Authors
- José Carlos Bouso
Published
Abstract
N,N-dimethyltryptamine (DMT) is a potent psychedelic naturally produced by many plants and animals, including humans. Whether or not DMT is significant to mammalian physiology, especially within the central nervous system, is a debate that started in the early 1960s and continues to this day. This review integrates historical and recent literature to clarify this issue, giving special attention to the most controversial subjects of DMT’s biosynthesis, its storage in synaptic vesicles and the activation receptors like sigma-1. Less discussed topics, like DMT’s metabolic regulation or the biased activation of serotonin receptors, are highlighted. We conclude that most of the arguments dismissing endogenous DMT’s relevance are based on obsolete data or misleading assumptions. Data strongly suggest that DMT can be relevant as a neurotransmitter, neuromodulator, hormone and immunomodulator, as well as being important to pregnancy and development. Key experiments are addressed to definitely prove what specific roles DMT plays in mammalian physiology.
Research Summary of 'Significance of mammalian N, N-dimethyltryptamine (DMT): A 60-year-old debate'
Introduction
N,N-dimethyltryptamine (DMT) is a potent psychedelic naturally produced by many plants and animals, including humans, and is structurally and metabolically related to serotonin, tryptamine, and melatonin. Whether endogenous mammalian DMT plays a meaningful physiological role within the central nervous system has been debated for over 60 years: initial detections in the 1960s were met with scepticism given the apparently small quantities involved, and the absence of a compelling pharmacological mechanism consistent with a trace amine status has perpetuated uncertainty. This review aimed to resolve the question of endogenous DMT's physiological significance by integrating historical and recent literature on four core issues: the quantity of DMT present in the mammalian CNS; the enzymatic capacity for its biosynthesis and degradation in neural tissue; whether DMT can be stored in synaptic vesicles and act as a neurotransmitter; and which receptors are activated by endogenous DMT concentrations, with particular attention to the 5-HT2A receptor, trace amine-associated receptors (TAARs), and the sigma-1 receptor.
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Jiménez, J. H., & Bouso, J. C. (2022). Significance of mammalian N, N-dimethyltryptamine (DMT): A 60-year-old debate. Journal of Psychopharmacology, 36(8), 905-919. https://doi.org/10.1177/02698811221104054
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