Endogenous psychoactive tryptamines reconsidered: an anxiolytic role

[Lehendakari]

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.

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