AADC

Does the human body make DMT?

Answer: The substance DMT is known to be a psychedelic with hallucinogenic properties, and it is believed the human body synthesizes the substance endogenously.

DMT human body endogenous

N, N-dimethyltryptamine, also called DMT, is a known psychedelic chemical. DMT can produce a change in perception, causing a person's visual experiences to be more robust. Furthermore, DMT can alter the mindstate of a person, leading to increased creativity or a dream-like state, the neural basis of which is not fully understood even in the absence of DMT.

When the substance was first synthesized by the Canadian chemist Richard Manske in 1931, it was not tested for its psychoactive properties in humans. Later, in 1956, DMT was chemically extracted from a plant, and was self administered by the scientist who discovered it, Stephen Szara. DMT is the major ingredient of ayahuasca, a tea that is brewed for spiritual and religious applications.

A theory proposed that endogenous production of DMT was involved in the clinical presentation of schizophrenia and psychosis. Elevated levels of the compound were observed in these populations, especially in the urine or blood. However, the results of the experiments concluded that the small amount of DMT was only a metabolite produced after some other chemical breakdown.

Endogenous synthesis / metabolism of DMT

As it turns out, the human body has the biosynthetic enzymes necessary to create DMT. The starting molecule in the biosynthetic pathway is tryptophan, a dietary amino acid. Tryptophan is processed by the enzyme aromatic acid decarboxylase (AADC) into tryptamine. Then, the enzyme indole-N-methyltransferase (INMT) adds two methyl groups onto tryptamine in a stepwise pattern, which results in N-methyltryptamine (NMT) and then DMT.

The body also has endogenous enzymes that break down (metabolize) many of these compounds. For example, the enzyme monoamine oxidase breaks down tryptamine, NMT, and DMT. (N, N-Dimethyltryptamine (DMT), an Endogenous Hallucinogen: Past, Present, and Future Research to Determine Its Role and Function)

Pharmacological action of DMT

The actual protein receptor targets of DMT are still not fully known. As with the other psychedelic compounds, such as the more well known LSD, DMT interacts with and activates the serotonin 5-HT2A receptor (Serotonin and lysergic acid diethylamide binding in rat brain membranes: Relationship to post-synaptic serotonin receptors.) This receptor is a common target of a variety of psychedelic or hallucinogenic drugs, and is believed to mediate the psychotropic effects of drugs like LSD.

But, DMT probably activates other receptors in the nervous system as well. For example, some doses of DMT produces a variety of movement disorders, and these do not appear to be mediated by serotonin (Behavioural changes induced by N,N-dimethyltryptamine in rodents).

One additional target that has been demonstrated is the sigma-1 receptor. Mistakenly first characterized as an opioid receptor, it was found to interact with DMT, but not the opioid peptides. (The Hallucinogen N,N-Dimethyltryptamine (DMT) Is an Endogenous Sigma-1 Receptor Regulator)

The sigma-1 receptor, or Sig-1R, signals via a different mechanism than most other receptors. Instead of being expressed on the cell surface, the sig-1R is found at the interface between the mitochondria and the endoplasmic reticulum, a region of the cell called the mitochondria-associated ER membrane. At low levels of DMT, as is found in the body, the sig-1R acts as a chaperone that stabilizes the IP3 receptor, which enhances calcium influx to the mitochondria, then triggering the beginning of the the tricarboxylic acid cycle to produce ATP.