Szára, who later worked for the United States National Institutes of Health, had turned his attention to DMT after his order for LSD from the Swiss company Sandoz Laboratories was rejected on the grounds that the powerful psychotropic could be dangerous in the hands of a communist country.

Other means of consumption such as vaporizing, injecting, or insufflating the drug can produce powerful hallucinations for a short time (usually less than half an hour), as the DMT reaches the brain before it can be metabolized by the body's natural monoamine oxidase.

[20][21] SPL026 (DMT fumarate) is currently undergoing phase II clinical trials investigating its use alongside supportive psychotherapy as a potential treatment for major depressive disorder.

[27] Several scientific experimental studies have tried to measure subjective experiences of altered states of consciousness induced by drugs under highly controlled and safe conditions.

[28] In contrast, responses produced by higher doses (0.2 and 0.4 mg/kg) researchers labeled as "hallucinogenic" that elicited "intensely colored, rapidly moving display of visual images, formed, abstract or both".

[28] A 1995 study by Adolf Dittrich and Daniel Lamparter found that the DMT-induced altered state of consciousness (ASC) is strongly influenced by habitual rather than situative factors.

[11] Strassman noted similarities between self-reports of his DMT study participants' encounters with these "entities", and mythological descriptions of figures such as Ḥayyot haq-Qodesh in ancient religions, including both angels and demons.

[47] A 2019 large-scale study pointed that ketamine, Salvia divinorum, and DMT (and other classical psychedelic substances) may be linked to near-death experiences due to the semantic similarity of reports associated with the use of psychoactive compounds and NDE narratives, but the study concluded that with the current data it is neither possible to corroborate nor refute the hypothesis that the release of an endogenous ketamine-like neuroprotective agent underlies NDE phenomenology.

[55] In 2011, Nicholas Cozzi of the University of Wisconsin School of Medicine and Public Health, and three other researchers, concluded that INMT, an enzyme that is associated with the biosynthesis of DMT and endogenous hallucinogens is present in the non-human primate (rhesus macaque) pineal gland, retinal ganglion neurons, and spinal cord.

[43] DMT may trigger psychological reactions, known colloquially as a "bad trip", such as intense fear, paranoia, anxiety, panic attacks, and substance-induced psychosis, particularly in predisposed individuals.

[26] A study examining substance use disorder for DSM-IV reported that almost no hallucinogens produced dependence, unlike psychoactive drugs of other classes such as stimulants and depressants.

[67][57] Serotonin syndrome has also been reported with tricyclic antidepressants, opiates, analgesic, and antimigraine drugs; it is advised to exercise caution when an individual had used dextromethorphan (DXM), MDMA, ginseng, or St. John's wort recently.

[citation needed] In a study conducted from 1990 through 1995, University of New Mexico psychiatrist Rick Strassman found that some volunteers injected with high doses of DMT reported experiences with perceived alien entities.

In addition, Jurema (Mimosa tenuiflora) shows evidence of DMT content: the pink layer in the inner rootbark of this small tree contains a high concentration of N,N-DMT.

[citation needed] Taken orally with an RIMA, DMT produces a long-lasting (over three hours), slow, deep metaphysical experience similar to that of psilocybin mushrooms, but more intense.

[80][81] In general, its discovery as a natural product is credited to Brazilian chemist and microbiologist Oswaldo Gonçalves de Lima, who isolated an alkaloid he named nigerina (nigerine) from the root bark of Mimosa tenuiflora in 1946.

[77] It was only in 1959, when Gonçalves de Lima provided American chemists a sample of Mimosa tenuiflora roots, that DMT was unequivocally identified in this plant material.

[77][83] Less ambiguous is the case of isolation and formal identification of DMT in 1955 in seeds and pods of Anadenanthera peregrina by a team of American chemists led by Evan Horning (1916–1993).

In 1957, American chemists Francis Hochstein and Anita Paradies identified DMT in an "aqueous extract" of leaves of a plant they named Prestonia amazonicum [sic] and described as "commonly mixed" with B.

[89] The lack of a proper botanical identification of Prestonia amazonica in this study led American ethnobotanist Richard Evans Schultes (1915–2001) and other scientists to raise serious doubts about the claimed plant identity.

[92] Better evidence was produced in 1965 by French pharmacologist Jacques Poisson, who isolated DMT as a sole alkaloid from leaves, provided and used by Aguaruna Indians, identified as having come from the vine Diplopterys cabrerana (then known as Banisteriopsis rusbyana).

[91] Published in 1970, the first identification of DMT in the plant Psychotria viridis,[82] another common additive of ayahuasca, was made by a team of American researchers led by pharmacologist Ara der Marderosian.

[97][51] From then on, two major complementary lines of evidence have been investigated: localization and further characterization of the N-methyltransferase enzyme, and analytical studies looking for endogenously produced DMT in body fluids and tissues.

[111] N,N-Dimethyltryptamine (DMT), a psychedelic compound identified endogenously in mammals, is biosynthesized by aromatic L-amino acid decarboxylase (AADC) and indolethylamine-N-methyltransferase (INMT).

Additionally, extracellular concentrations of DMT in the cerebral cortex of normal behaving rats, with or without the pineal gland, were similar to those of canonical monoamine neurotransmitters including serotonin.

[55] DMT may be measured in blood, plasma or urine using chromatographic techniques as a diagnostic tool in clinical poisoning situations or to aid in the medicolegal investigation of suspicious deaths.

[97] Also, robust evidence that INMT can catalyze transmethylation of tryptamine into NMT and DMT could be provided with reverse isotope dilution analysis coupled to mass spectrometry for rabbit[123][124] and human[125] lung during the early 1970s.

[102][135] Intermediate levels of expression are found in human heart, skeletal muscle, trachea, stomach, small intestine, pancreas, testis, prostate, placenta, lymph node, and spinal cord.

[148] This may be of importance because chronic or frequent uses of serotonergic drugs showing preferential high affinity and clear agonism at 5-HT2B receptor have been causally linked to valvular heart disease.

[177] DMT peak level concentrations (Cmax) measured in whole blood after intramuscular (IM) injection (0.7 mg/kg, n = 11)[178] and in plasma following intravenous (IV) administration (0.4 mg/kg, n = 10)[28] of fully psychedelic doses are in the range of around 14 to 154 μg/L and 32 to 204 μg/L, respectively.