DMT: Difference between revisions

| classes          = Classic Psychedelic, Tryptamine

| legal            = Schedule I (United States)

| intro            = The earliest record of human use of DMT-bearing medicines comes from the Amazon and the Orinoco, where indigenous peoples have for centuries prepared visionary preparations from plants that contain the molecule. The most widespread of these is ayahuasca, a brew of the Banisteriopsis caapi vine cooked together with the leaves of Psychotria viridis or related DMT-bearing companions. The vine contains harmine and harmaline, which inhibit monoamine oxidase and allow orally administered DMT, which would otherwise be destroyed in the gut, to reach the brain. The pairing is the technical accomplishment that defines the tradition. Whether indigenous knowledge of the pairing predates European contact in its present form is debated by ethnobotanists, but the brew was encountered by missionaries in the upper Amazon in the 19th century and entered ethnographic literature through Richard Spruce's botanical work in the 1850s and, later, through Richard Evans Schultes at the Harvard Botanical Museum.<ref name="schultes1969">Schultes RE. Hallucinogens of plant origin. Science. 1969;163(3864):245-254. PMID: 4883616.</ref>

The other major lineage is the snuffs. Anadenanthera peregrina and Anadenanthera colubrina, leguminous trees of the South American lowlands, yield seeds that indigenous peoples have ground, toasted, and inhaled as the snuffs cohoba and yopo. Cohoba was reported by the Spanish chronicler Ramón Pané at Hispaniola in 1496, in an account commissioned by Columbus, making the European written record of DMT-bearing medicine more than four centuries old.

| history          = The chemistry came much later. The molecule itself was first synthesized in 1931 by the Canadian chemist Richard Helmuth Frederick Manske at the National Research Council laboratories in Ottawa, as part of a systematic study of the methyltryptamines.<ref name="manske1931">Manske RHF. A synthesis of the methyltryptamines and some derivatives. Canadian Journal of Research. 1931;5:592-600.</ref> At the time, no one knew the compound occurred in any plant. The natural-product identification came in 1946, when the Brazilian chemist Oswaldo Gonçalves de Lima isolated an alkaloid he called nigerine from the roots of Mimosa hostilis, the plant used in the northeastern Brazilian preparation known as the wine of jurema.<ref name="lima1946">Gonçalves de Lima O. Observações sobre o "vinho da Jurema" utilizado pelos índios Pancarú de Tacaratú (Pernambuco). Arquivos do Instituto de Pesquisas Agronômicas. 1946;4:45-80.</ref> Nigerine was later shown to be DMT. In 1955, M. S. Fish, N. M. Johnson, and E. C. Horning identified DMT and related tryptamines as the active constituents of Anadenanthera peregrina seeds, finally connecting the 500-year-old cohoba record to the molecule.<ref name="fish1955">Fish MS, Johnson NM, Horning EC. Piptadenia alkaloids. Indole bases of P. peregrina (L.) Benth. and related species. Journal of the American Chemical Society. 1955;77(22):5892-5895.</ref>

The proof that DMT was psychoactive in humans is owed to Stephen Szára. A young Hungarian chemist and psychiatrist working in Budapest in the mid-1950s, Szára was studying the model-psychosis hypothesis and wanted to work with LSD. He wrote to Sandoz in Basel and was refused. Sandoz declined to send a powerful psychotropic compound across the Iron Curtain, fearing it would reach Communist hands. Szára turned instead to a molecule he could synthesize himself, and in 1956 administered DMT intramuscularly to a series of healthy volunteers, mostly young physician colleagues. The effects, brief, intense, and unmistakably psychedelic, were published the same year in Experientia.<ref name="szara1956">Szára S. Dimethyltryptamin: its metabolism in man; the relation to its psychotic effect to the serotonin metabolism. Experientia. 1956;12(11):441-442. PMID: 13384414.</ref> After the Hungarian uprising later that year, Szára emigrated, eventually joining the National Institute of Mental Health in the United States, where he and colleagues characterized DMT alongside its diethyl and dipropyl homologs.

The clinical-research era that followed was abbreviated by prohibition. In the United States, the Controlled Substances Act of 1970 placed DMT in Schedule I, the most restrictive category, and human research effectively ceased for two decades. The reopening came in the early 1990s, when Rick Strassman obtained the regulatory permissions required to administer intravenous DMT to healthy volunteers at the University of New Mexico. Strassman's group published the first modern dose-response work in 1994, characterizing the neuroendocrine, autonomic, and subjective effects of the molecule and reviving the field.<ref name="strassman1994a">Strassman RJ, Qualls CR. Dose-response study of N,N-dimethyltryptamine in humans. I. Neuroendocrine, autonomic, and cardiovascular effects. Archives of General Psychiatry. 1994;51(2):85-97. PMID: 8297216.</ref><ref name="strassman1994b">Strassman RJ, Qualls CR, Uhlenhuth EH, Kellner R. Dose-response study of N,N-dimethyltryptamine in humans. II. Subjective effects and preliminary results of a new rating scale. Archives of General Psychiatry. 1994;51(2):98-108. PMID: 8297217.</ref>

DMT is a substituted tryptamine whose effects in the central nervous system are mediated primarily by partial agonism at the serotonin 5-HT2A receptor, with additional activity at other 5-HT receptor subtypes and, at higher concentrations, at sigma-1 and trace amine-associated receptors.<ref name="nichols2016">Nichols DE. Psychedelics. Pharmacological Reviews. 2016;68(2):264-355. PMID: 26841800.</ref> Taken orally without an accompanying inhibitor, DMT is inactive: monoamine oxidase A in the gut and liver metabolizes it before it reaches the brain. Inhalation, insufflation, or parenteral administration bypass this first-pass destruction, as does oral co-administration with a monoamine oxidase inhibitor, which is the pharmacological logic of ayahuasca. Plasma elimination half-life after intravenous administration is approximately 9 to 12 minutes, among the shortest of any psychoactive medicine in clinical use.