DMT
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.
Commentary
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.[2] 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.[3] 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.[4]
Commentary
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.[5] 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.
Commentary
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.[6][7]
The legal status of DMT-bearing preparations has been litigated as well as legislated. In 2006, the United States Supreme Court ruled unanimously in Gonzales v. O Centro Espírita Beneficente União do Vegetal that the federal government could not bar the União do Vegetal, a Brazilian-origin religious community, from sacramental use of ayahuasca within the United States, applying the Religious Freedom Restoration Act. The decision opened a narrow legal channel for ayahuasca use that remains in place.
The endogenous question runs alongside the human-use history. DMT was identified in human urine in 1965 and in human blood and cerebrospinal fluid in the years that followed; it is now established as a normal, trace constituent of the mammalian body, though its physiological role remains the subject of active investigation.[8] The molecule's presence in the brain has driven a long-running and unresolved discussion about whether endogenous DMT contributes to ordinary or pathological states of consciousness, a question that became prominent during the modern research renaissance.
Commentary
That renaissance has continued. Exploratory clinical work in the 2020s has examined intravenous DMT in healthy volunteers and in patients with major depressive disorder.[9] The compound's very short duration of action, roughly twenty minutes when given by inhalation or intravenous infusion, has driven interest in formulations and infusion schemes designed to extend or control the experience for therapeutic purposes.
DMT is not currently licensed as a medicine in any major jurisdiction. Clinical investigation is active in major depressive disorder, with phase I and II trials of intravenous formulations underway. Ayahuasca, the orally active preparation, has been studied in a randomized placebo-controlled trial for treatment-resistant depression, with rapid antidepressant effects reported at follow-up.[10] Outside of formal trials, DMT-containing preparations are used in religious and ceremonial settings under varying legal frameworks.
Commentary
DMT is a Schedule I controlled substance in the United States and is similarly restricted under the 1971 United Nations Convention on Psychotropic Substances. The Gonzales v. O Centro decision (2006) established a religious-use exemption for the União do Vegetal; the Santo Daime church has subsequently obtained similar exemptions in several jurisdictions. Brazil, the country of the ayahuasca traditions, has permitted religious use of the brew since the late 1980s.
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Pharmacodynamics
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.[11] 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.
Doses used outside the research setting are not standardized. Harm-reduction documentation such as the Erowid DMT Vault records inhaled use ranging from a few milligrams to roughly sixty milligrams, with effects beginning within about a minute and largely resolving within twenty minutes.[12] Because DMT is active in the range of tens of milligrams and the purity of any non-pharmaceutical preparation is uncertain, the dose actually received outside a clinical setting is difficult to know, a point of practical relevance when a clinician is assessing a patient's reported exposure.
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See also
References
- ↑ Schultes RE. Hallucinogens of plant origin. Science. 1969;163(3864):245-254. PMID: 4883616.
- ↑ Manske RHF. A synthesis of the methyltryptamines and some derivatives. Canadian Journal of Research. 1931;5:592-600.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ Barker SA. N,N-Dimethyltryptamine (DMT), an Endogenous Hallucinogen. Frontiers in Neuroscience. 2018;12:536. PMID: 30127713.
- ↑ D'Souza DC, Syed SA, Flynn LT, Safi-Aghdam H, et al. Exploratory study of the dose-related safety, tolerability, and efficacy of dimethyltryptamine (DMT) in healthy volunteers and major depressive disorder. Neuropsychopharmacology. 2022;47(10):1854-1862. PMID: 35660802.
- ↑ Palhano-Fontes F, Barreto D, Onias H, Andrade KC, et al. Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial. Psychological Medicine. 2019;49(4):655-663. PMID: 29903051.
- ↑ Nichols DE. Psychedelics. Pharmacological Reviews. 2016;68(2):264-355. PMID: 26841800.
- ↑ Erowid. DMT Dosage. Erowid DMT Vault, 1997, last modified 21 February 2015. https://www.erowid.org/chemicals/dmt/dmt_dose.shtml (accessed 21 May 2026).