Significance of mammalian N, N-dimethyltryptamine (DMT): A 60-year-old debate.

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.

Dimethyltryptamine: Endogenous Role and Therapeutic Potential.

N, N-dimethyltryptamine (DMT) is an indole alkaloid produced by a number of plants and animals, including humans. Its psychoactive effects were first described in 1956 by Stephen Szára, but have been exploited for centuries by South American indigenous populations in the form of ayahuasca. In the present review, we assess the state of the art regarding a putative role for endogenous DMT and potential clinical applications of ayahuasca and DMT. A review assessing the pharmacological profile of DMT and its clinical effects in humans was performed using the PubMed data base until 5 August 2018 with the words: ayahuasca and N,N-dimethyltryptamine. While the role of endogenous DMT remains unclear, ayahuasca has promising results in anxiety, depression and substance dependence. Since ayahuasca has a good safety profile, it is crucial to conduct further research aimed at developing new treatments for psychiatric disorders.

Basics of the medical use of ayahuasca: physiology of dimethyltryptamine.

Ayahuasca is a brew made of two admixture plants containing dimethyltryptamine (DMT) and b-carbolines (harmine and tetrahydroharmine). The indigenous groups of the Amazonas basin have been using it for centuries as an ethnomedical substance in healing and spiritual-religious rituals. During the last two decades the brew has raised increased scientific and public interest worldwide about its healing effects. Present paper addresses the therapeutic potentials of ayahuasca use and outlines the cellular mechanisms behind - in focus of the Q-1 receptor mediated action of DMT. The scientific investigation of ayahuasca is complicated by methodical problems, legal issues, and sociocultural pre-conceptions.

Endogenous psychoactive tryptamines reconsidered: an anxiolytic role for dimethyltryptamine.

The presence of the potent hallucinogenic psychoactive chemical N,N-dimethyltryptamine (DMT) in the human body has puzzled scientists for decades. Endogenous DMT was investigated in the 1960s and 1970s and it was proposed that DMT was involved in psychosis and schizophrenia. This hypothesis developed from comparisons of the blood and urine of schizophrenic and control subjects. However, much of this research proved inconclusive and conventional thinking has since held that trace levels of DMT, and other endogenous psychoactive tryptamines, are insignificant metabolic byproducts. The recent discovery of a G-protein-coupled, human trace amine receptor has triggered a reappraisal of the role of compounds present in limited concentrations in biological systems. Interestingly enough, DMT and other psychoactive tryptamine hallucinogens elicit a robust response at the trace amine receptor. While it is currently accepted that serotonin 5-HT(2A) receptors play a pivotal role in the activity of hallucinogenic/psychedelic compounds, we propose that the effects induced by exogenous DMT administration, especially at low doses, are due in part to activity at the trace amine receptor. Furthermore, we suggest that endogenous DMT interacts with the TA receptor to produce a calm and relaxed mental state, which may suppress, rather than promote, symptoms of psychosis. This hypothesis may help explain the inconsistency in the early analysis of endogenous DMT in humans. Finally, we propose that amphetamine action at the TA receptor may contribute to the calming effects of amphetamine and related drugs, especially at low doses.

Urinary excretion of dimethyltryptamine in liver disease.

The urinary excretion of N,N-dimethyltryptamine (DMT) was higher in patients with severe liver disease than in normal subjects. This difference remained significant when patients with all grades of hepatic encephalopathy were excluded. Patients with liver disease whose mental states were normal excreted amounts of DMT similar to those of patients with a hospital diagnosis of schizophrenia.