DMT

Classic Psychedelic, Tryptamine

DMT

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.

“Pendell's corner

In the old days, for pot-smokers and acid heads, there was pot, there was acid, and then, beyond them all, there was DMT.

— Dale Pendell, Pharmako/Gnosis, p. 227

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. 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. 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.

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. 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.

“Pendell's corner

Deep psychonauts of DMT space usually agree that it is very difficult to bring anything back from the space, or to talk about it in any way with someone who hasn't been there.

— Dale Pendell, Pharmako/Gnosis, p. 227

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.

“Pendell's corner

DMT is now known to be widespread in the plant world, particularly in the grasses and the pea family. In trace amounts, as Alexander Shulgin titled a chapter in TIHKAL, "DMT is everywhere." It is also found in the human body, and in the human brain.

— Dale Pendell, Pharmako/Gnosis, p. 229

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. 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.

That renaissance has continued. Exploratory clinical work in the 2020s has examined intravenous DMT in healthy volunteers and in patients with major depressive disorder. 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.

“Pendell's corner

The main problem of DMT art, aside from the ubiquitous presence of spiritual clichés, is its embarrassing obviousness. Subtlety is not one of DMT's qualities.

— Dale Pendell, Pharmako/Gnosis, p. 233

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. Outside of formal trials, DMT-containing preparations are used in religious and ceremonial settings under varying legal frameworks.

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.

“Pendell's corner

And a bit of whatever the place is where magic lives. All adding up to a very spicy and seductive song. THERE IS MEANING HERE. THE SECRET IS HERE.

— Dale Pendell, Pharmako/Gnosis, p. 236

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Pharmacodynamics

“Pendell's corner

There are fibers of geometry that dumbfound even sailors.

— Dale Pendell, Pharmako/Gnosis, p. 235

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. 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.

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See also

Ayahuasca, LSD

References

Summary

Classes

Classic Psychedelic, Tryptamine

Common uses

Pharmacy

Pharmacology

Duration

About 20 minutes

Half-life

9–12 minutes (intravenous)

Legal status

Schedule I (United States)

Purported mechanism

5-HT2A partial agonist; sigma-1 agonist