Dimethyltryptamine

• 1. Introduction

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  Dimethyltryptamine, better known as DMT, picked up a nickname in 1960s America: the "businessman's trip." The label stuck because of speed. A user could reach the full depth of a psychedelic experience in far less time than LSD or psilocybin mushrooms allowed. DMT is a serotonergic hallucinogen of the tryptamine family, and it occurs naturally in many plants and animals. Various cultures have prepared it for ritual use as an entheogen, a substance taken for spiritual purposes. Today it is also in clinical trials for treatment-resistant depression.

  The molecule leaves a string of puzzles behind it. Why does a drug that does nothing when swallowed sit at the heart of a traditional Amazonian brew? Who first worked out what it does to the mind, and why did he turn to it? Why do so many people report meeting what seem to be independent beings? And does the human body make its own supply? Researchers have chased that last question for decades, and the answer is still contested.

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• 2. Plants, Brews, And Doses

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  Psychotria viridis, Mimosa tenuiflora, and Diplopterys cabrerana are among the notable plants that contain DMT. Amazonian peoples and others in Central and South America have long used such plants as an entheogen and for shamanistic purposes. The best known preparation is ayahuasca, a boiled brew that pairs a DMT-bearing plant with a second plant, Banisteriopsis caapi. The DMT plant may be Psychotria viridis, Psychotria carthagenensis, or Diplopterys cabrerana. Recipes vary widely, and some brews are made with plants that contain no DMT at all. DMT is usually the main active ingredient. Hallucinogenic snuffs made from Virola or Anadenanthera plants also hold DMT, but only as a minor alkaloid beside 5-MeO-DMT and bufotenin.

  Banisteriopsis caapi matters for a chemical reason. The enzyme monoamine oxidase A breaks DMT down so quickly that DMT swallowed on its own is inactive. Harmala alkaloids such as harmine and harmaline block that enzyme, and so does a pharmaceutical called moclobemide. Peganum harmala is another plant that supplies harmala alkaloids, which lets DMT work by mouth. When the ingredients are not naturally sourced, the pairing is called pharmahuasca. Changa is a separate preparation, a plant-derived form of DMT meant for smoking.

  Alexander Shulgin set out many dose figures in his book TiHKAL, short for Tryptamines I Have Known and Loved. For DMT alone, he gave 60 to 100 mg by intramuscular injection, under the skin, or smoked. Swallowed without an inhibitor, even 150 to 350 mg, and up to 1,000 mg, produced no effects. By vein the doses are far smaller. A 4 mg dose could not be told from placebo, and 8 mg caused physical effects without psychoactive ones. At 15 mg the psychedelic effects reached threshold, and at 30 mg they were strong.

  Smoked DMT takes hold within 10 to 15 seconds, while injections need 2 to 5 minutes. Inhaled DMT lasts 5 to 20 minutes, averaging 12, and intramuscular injection lasts 30 to 60 minutes. Pairing oral DMT with an inhibitor gives a slow start, within an hour, but a duration of 4 to 6 hours. More recent guidance recommends 50 mg of DMT with 100 mg of harmaline. The harmala alkaloid is usually taken first, with the DMT following 15 to 20 minutes later.

  A newer method called DMTx, continuous intravenous infusion, stretches the experience to hours. It starts at 0.6 mg per minute for a low dose, and 1.2 mg per minute is called the "good effect" dose. Vape pens have also been made as an alternative to smoking. In Shulgin's oral work, harmine behaved differently from harmaline. Harmine produced no psychoactive effects of its own at doses of up to at least 300 mg.

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• 3. The Discovery Trail

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  Plant sources of DMT had served as an entheogen in South America for thousands of years before the Canadian chemist Richard Manske first synthesized the compound in 1931. Credit for finding it in nature usually goes to Oswaldo Gonçalves de Lima, a Brazilian chemist and microbiologist. In 1946 he isolated an alkaloid he called nigerina from the root bark of Mimosa tenuiflora. Jonathan Ott later reviewed the case. The formula Gonçalves de Lima reported contains an atom of oxygen, so it can match only an impure or partial form of DMT. Certainty came in 1959, when he gave American chemists a sample of Mimosa tenuiflora roots and DMT was clearly identified in them.

  A cleaner case dates to 1955. A team of American chemists led by Evan Horning, who lived from 1916 to 1993, isolated and identified DMT in the seeds and pods of Anadenanthera peregrina.

  Stephen Szára, a Hungarian chemist and psychiatrist, uncovered the hallucinogenic effects of DMT in 1956. He had tried to order LSD from the Swiss company Sandoz Laboratories. The order was refused because such a powerful psychotropic could be dangerous in the hands of a communist country. Szára researched DMT instead and later worked for the United States National Institutes of Health. His paper used synthetic DMT made by the Speeter-Anthony route and gave it by intramuscular injection to 20 volunteers. Urine samples were collected to identify the metabolites. This work is considered the link between DMT's chemical structure and its cultural use as a psychoactive and religious sacrament.

  In 1957, the American chemists Francis Hochstein and Anita Paradies reported DMT in a leaf extract from a plant they called Prestonia amazonicum, said to be commonly mixed with Banisteriopsis caapi. The study lacked a proper botanical identification, so the ethnobotanist Richard Evans Schultes (1915-2001) and others doubted the plant's identity. The mistake likely led the writer William Burroughs to regard the DMT he tried in Tangier in 1961 as "Prestonia". Better evidence arrived in 1965 from the French pharmacologist Jacques Poisson. He isolated DMT as the sole alkaloid in leaves supplied by Aguaruna Indians from the vine Diplopterys cabrerana, then known as Banisteriopsis rusbyana. In 1970 a team led by the pharmacologist Ara der Marderosian first found DMT in Psychotria viridis, using leaves from the Kaxinawá people. They were also the first to identify it in an ayahuasca decoction, made by those same people.

  Since 1955, DMT has turned up in at least fifty plant species belonging to ten families. It has also been found in at least four animal species, including one gorgonian and three mammals, humans among them.

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• 4. Inside The Experience

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  In the 1990s, Rick Strassman and his colleagues ran a five-year DMT study at the University of New Mexico. Participants received the drug by intravenous injection. Low doses of 0.01 and 0.05 mg/kg produced aesthetic and emotional responses but no hallucinations, and 0.05 mg/kg was mildly mood-lifting and calming. At 0.2 and 0.4 mg/kg, researchers labeled the responses hallucinogenic, describing an "intensely colored, rapidly moving display of visual images, formed, abstract or both". Vision was affected most, with fewer auditory hallucinations. Participants also described bodily dissociation, euphoria, calm, fear, and anxiety. This dose-dependent pattern matches anonymous online trip reports, where users describe "breakthroughs" above certain doses.

  Strassman stressed that context shapes the experience. He claimed DMT has no beneficial effects of itself, and that when and where people take it plays an important role. A 1995 study by Adolf Dittrich and Daniel Lamparter pointed in a different direction. It found that DMT's altered state was shaped more by habitual factors than by the situation. The researchers used three dimensions of the APZ questionnaire. Oceanic boundlessness covers dissolving ego boundaries, mostly with positive emotions. Anxious ego-dissolution means disordered thoughts and reduced self-control. Visionary restructuralization covers visual and auditory illusions and hallucinations. Effects were strong on the first and third dimensions, especially with DMT.

  Shulgin's accounts in TiHKAL read like a catalogue of the strange. With eyes closed, people saw kaleidoscopic colors and fast-moving geometric patterns. With eyes open, patterns could turn into the heads of animals, and people's faces could seem to be masks. Others felt time stretch, felt they had died or lost their body, or felt they were moving at the speed of light. Some felt they were gazing upon the entire universe. Emotions ranged from euphoria to dread and doom, and one entry is simply wanting one's mother. Physical effects included dilated pupils, tingling, sweating, and a faster heart rate. Other accounts mention hyperbolic geometry and Escher-like impossible objects.

  Oral DMT with harmaline, as Shulgin recorded it, brought infinitely repeated wavy sheets of pattern, enhanced music, and an afterglow. It could also bring nausea, difficulty walking, depression, and a feeling of being psychotic. Harmaline has hallucinogenic effects of its own at doses of around 150 mg or more.

  A dose-response study of intravenous DMT in people measured slight rises in blood pressure, heart rate, pupil diameter, and rectal temperature. Blood levels of beta-endorphin, corticotropin, cortisol, and prolactin also rose. Growth hormone climbed equally at every dose, while melatonin was unaffected.

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• 5. Machine Elves And Entities

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  Terence McKenna coined the term machine elf for the beings he met in DMT "hyperspace". The ethnobotanist also used the names fractal elves and self-transforming machine elves. He first encountered them after smoking DMT in Berkeley in 1965. His speculation about the hyperdimensional space inspired a great many artists and musicians. His vivid accounts also fed a debate about what the entities mean among participants in a networked cultural underground. Cliff Pickover wrote about the same experience in his book Sex, Drugs, Einstein, & Elves.

  Stephen Szára recorded an early version of these visions in 1958, in a study of psychotic patients. One subject described "strange creatures, dwarves or something" at the start of a trip. Later researchers describe humanoid and animal forms, with "little people" such as gnomes, elves, and imps being common. Some of Strassman's participants saw insects and aliens instead. Others heard loud sounds, one reporting "the elves laughing or talking at high volume, chattering, twittering". These reports left Strassman wondering "if I was getting in over my head with this research."

  Strassman compared his participants' reports to figures from ancient religions. The mechanized wheels, gears, and machinery they described resembled the Living Creatures and Ophanim in visions in the Hebrew Bible. He also linked the chattering sounds to the Hayyoth in the Book of Ezekiel, and he suggested a common neuropsychopharmacological origin. The more positive entities, he argued, are analogous to angels, which the medieval Jewish philosophers he relied on portray as God's intermediaries. He and others speculated that the same kind of hallucination, possibly driven by endogenously occurring DMT, may lie behind alien abduction experiences.

  Robin Carhart-Harris and David E. Nichols, among others, believe the entities are merely illusions and hallucinations. Andrew Gallimore takes the opposite view. He believes the encounters are real and genuine interactions with other-dimensional beings.

  A 2018 study found significant relationships between DMT experiences and near-death experiences. In 2019, a large-scale study found that reports linked to ketamine, Salvia divinorum, and DMT resemble near-death narratives in meaning. That study concluded the data could neither corroborate nor refute the idea that release of an endogenous ketamine-like neuroprotective agent underlies near-death experiences.

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• 6. The Body's Own DMT

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  Through the 1950s, some scientists wondered whether the body makes its own psychoactive chemicals, which might explain the hallucinations of some psychiatric diseases. This idea is known as the transmethylation hypothesis. In 1961, Julius Axelrod published in Science his discovery of an enzyme in a rabbit's lung that could turn tryptamine into DMT. Interest in endogenous DMT has continued ever since, along two lines. One line studies the enzyme itself. The other looks for DMT in body fluids and tissues.

  The recipe is simple. An enzyme called AADC strips a carboxyl group from the amino acid tryptophan to give tryptamine. A second enzyme, INMT, then passes a methyl group from a cofactor called SAM onto tryptamine. The result is N-methyltryptamine, and the same step repeated gives DMT. Two products of the reaction, SAH and DMT itself, were among the most potent inhibitors of rabbit INMT activity.

  The first claimed detection in mammals came in June 1965. German researchers F. Franzen and H. Gross reported finding and measuring DMT and bufotenin in human blood and urine. Four months later their method was strongly criticized. Early-1970s work using reverse isotope dilution analysis and mass spectrometry gave robust evidence that INMT could make DMT in rabbit and human lung. Trouble came in 1974-1975, when researchers realized that thin layer chromatography could not tell DMT apart from tetrahydro-β-carbolines. Earlier claims of DMT synthesis in bird and mammal brains were doubted, and replications with better methods failed to find it in rat and human brain tissue. A 1978 study judged the conversion in rat brain real but insignificant.

  A gene encoding INMT sits on human chromosome 7. Early blot analyses found its messenger RNA highly expressed in human thyroid, adrenal gland, and lung, and absent from whole brain. In 2011, Nicholas Cozzi of the University of Wisconsin School of Medicine and Public Health and three colleagues found INMT in the pineal gland, retinal ganglion neurons, and spinal cord of the rhesus macaque. A 2020 study using in-situ hybridization, a far more accurate tool, found it in the human cerebral cortex, choroid plexus, and pineal gland.

  A 2005 study used the most sensitive and selective method ever applied to endogenous DMT, with detection limits 12 to 200 fold lower than the best of the 1970s. In 2013, researchers found DMT in fluid sampled from a rat's pineal gland. Experiments in 2019 showed that the rat brain can synthesize and release DMT at levels comparable to known monoamine neurotransmitters. DMT in rat visual cortex rose after experimentally induced cardiac arrest, whether or not the pineal gland was intact.

  Strassman assumed that more than half of the DMT made by the pineal gland's acidophilic cells is released before and during death, at 2.5 to 3.4 mg/kg. David Nichols criticized that claim. He noted that the pineal gland does not seem to make DMT in meaningful amounts, and that removing it produces symptoms consistent only with losing melatonin. Nichols suggested that dynorphin and other endorphins explain the euphoria patients report during near-death experiences. Andrew Gallimore proposed in 2013 that DMT may once have been an ancestral neuromodulator, released in psychedelic concentrations during REM sleep, a function now lost.

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• 7. Receptors And Risks

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  DMT interacts most strongly with serotonin receptors, especially 5-HT2A, 5-HT1A, and 5-HT2C. Much of its psychedelic effect is attributed to activating 5-HT2A. The concentrations that work at the human 5-HT2A receptor in the lab, 0.118 to 0.983 μmol/L, match blood levels after a fully psychedelic dose. DMT is slightly more potent at 5-HT2C, so that receptor is implicated too.

  Twice-daily DMT sessions, five hours apart for five consecutive days, produced no tolerance to the subjective effects. A fully hallucinogenic dose also worked in people highly tolerant to LSD, so there was no cross-tolerance. Field reports describe a refractory period of only 15 to 30 minutes. One explanation is that DMT activates the Gq pathway of 5-HT2A without recruiting β-arrestin2, a protein linked to receptor downregulation. 5-MeO-DMT behaves in a similar way. Another view is that the very short duration explains the missing tolerance. Later studies using DMTx infusion did find rapid and moderate acute tolerance.

  Swallowed DMT is broken down by MAO enzymes in the liver and gut, mainly MAO-A, into indole-3-acetic acid. Intravenous DMT peaks in 2 to 3 minutes, while in ayahuasca the peak is delayed to 1.8 hours on average. The elimination half-life after an intravenous dose is 6 to 12 minutes, and elimination is through urine.

  A "bad trip" can bring intense fear, paranoia, panic attacks, and psychosis, particularly in predisposed people. DMT is considered non-addictive, and no withdrawal syndrome has been reported. No serious adverse effects of long-term use have been reported apart from acute cardiovascular events. Deaths have occurred. For oral DMT as ayahuasca, the lethal dose is estimated at 50 times a typical recreational dose.

  MAOIs such as those in ayahuasca can trigger life-threatening serotonin syndrome when combined with serotonergic medications such as SSRI antidepressants. Caution is advised after recent use of dextromethorphan, MDMA, ginseng, or St. John's wort. Yet a clinical study of people with depression found that SSRIs did not dull the effects of DMT. Those patients scored higher for mystical experience, emotional breakthrough, and ego dissolution. Mood stabilizers such as lithium may provoke seizure and dissociative effects when combined with psychedelics in people with bipolar disorder. Methysergide has been reported to greatly intensify DMT.

  Two lab assays showed DMT binding the 5-HT2B receptor with high affinity, at 0.108 and 0.184 μmol/L. That matters because chronic use of serotonergic drugs with strong affinity and clear agonism at 5-HT2B has been causally linked to valvular heart disease.

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• 8. Law And Medicine

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  The Convention on Psychotropic Substances controls DMT internationally, making it illegal to possess, buy, or sell without a licence. Ayahuasca brews and preparations are treated as lawful at that level. National rules differ. The United Kingdom and New Zealand class DMT as Class A, and the United States lists it as Schedule I under the Controlled Substances Act of 1970. India sets a minimum punishment of ten years. Sweden's supreme court ruled in 2018 that possessing processed plant material with significant DMT is illegal, while unprocessed material is legal.

  Between 2011 and 2012, the Australian federal government considered classing any plant containing DMT as a controlled plant. The plan collapsed in political embarrassment when officials realized it would make the golden wattle, Acacia pycnantha, Australia's official floral emblem, illegal. A related motion at the Therapeutic Goods Administration was withdrawn in May 2012.

  In December 2004, the United States Supreme Court lifted a stay so the Brazil-based União do Vegetal church could use its DMT-containing tea, called hoasca, in Christmas services. In Gonzales v. O Centro Espírita Beneficente União do Vegetal, arguments were heard on the 1st of November 2005. The court ruled unanimously in February 2006 that the government must allow the tea's import and use in ceremonies under the 1993 Religious Freedom Restoration Act. Three Santo Daime churches sued under the same law in 2008. In Church of the Holy Light of the Queen v. Mukasey, an Oregon court ruled they could import, distribute, and brew ayahuasca. Canada gave the Santo Daime Church Céu do Montréal a religious exemption in 2017, while a Santo Daime member's 2014 attempt in Ireland failed. In 2019, the city of Oakland decriminalized naturally derived psychedelics after a campaign by Decriminalize Nature.

  By 2018, e-cigarette cartridges and vape pens filled with DMT were being sold on the black market. Akasha Song once manufactured and sold DMT on the dark web and is said to have been the largest DMT producer and seller in history. Clandestine makers rarely synthesize DMT because tryptamine and oxalyl chloride are hard to obtain. They extract it from plants instead, using solvents such as naphtha or heptane.

  Short-acting psychedelics such as DMT and 5-MeO-DMT have shown rapid and sustained antidepressant effects in treatment-resistant depression. They may be more scalable than psilocybin, though larger controlled trials are needed. SPL026, an intravenous form of DMT fumarate, was tested in a Phase 1/2 trial in healthy volunteers and in patients with moderate-to-severe major depressive disorder. In a Phase 2a open-label trial, inhaled DMT produced high response and remission rates within 7 days, lasting up to 3 months. A single-day trial of vaporized DMT found up to 50% of participants still in remission a month later. DMT is also described as a psychoplastogen, a compound that promotes rapid and lasting neuroplasticity. A September 2020 study found that the DMT in ayahuasca promotes neurogenesis.

  VLS-01, a buccal film form of DMT, completed a Phase 1 trial in which side effects were mild or moderate. As of April 2026, Phase 2 trials are ongoing in the United States and Australia.

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