Dimethyltryptamine
Dimethyltryptamine, also known as N,''N-dimethyltryptamine, is a serotonergic hallucinogen and investigational drug of the tryptamine family that occurs naturally in many plants and animals. DMT is used as a psychedelic drug and prepared by various cultures for ritual purposes as an entheogen.
DMT has a rapid onset, intense effects, and a relatively short duration of action. For those reasons, DMT was known as the "businessman's trip" during the 1960s in the United States, as a user could access the full depth of a psychedelic experience in considerably less time than with other substances such as LSD or psilocybin mushrooms. DMT can be inhaled or injected and its effects depend on the dose, as well as the mode of administration. When inhaled or injected, the effects last about five to fifteen minutes. Effects can last three hours or more when orally ingested along with a monoamine oxidase inhibitor, such as the ayahuasca brew of many native Amazonian tribes. DMT induces intense, often indescribable subjective experiences involving vivid visual hallucinations, altered sensory perception, ego dissolution, and encounters with seemingly autonomous entities. DMT is generally considered non-addictive with low dependence and no tolerance buildup, but it may cause acute psychological distress or cardiovascular effects, especially in predisposed individuals.
DMT was first synthesized in 1931. It is a functional and structural analogue of other psychedelic tryptamines such as 4-AcO-DMT, psilocybin, psilocin, O''-methylbufotenin, and bufotenin. Parts of the structure of DMT occur within some important biomolecules like serotonin and melatonin, making them structural analogues of DMT.
DMT exhibits broad and variable binding affinities across numerous receptors, showing its strongest interactions with serotonin receptors, especially 5-HT2A, 5-HT1A, and 5-HT2C, which are believed to mediate its psychedelic effects. Endogenous DMT, a psychedelic compound, is naturally produced in mammals, with evidence showing its synthesis and presence in brain and body tissues, though its exact roles and origins remain debated. DMT is internationally illegal without authorization, with most countries banning its possession and trade, though some allow religious use of ayahuasca, a DMT-containing decoction. Short-acting psychedelics like DMT are considered scalable alternatives to longer-acting drugs like psilocybin for potential clinical use. DMT is currently undergoing clinical trials for treatment-resistant depression.
Use and effects
Forms, routes, and doses
DMT is used either in pure form or in the form of naturally sourced materials. It occurs naturally in many plants, among the more notable species including Psychotria viridis, Mimosa tenuiflora, and Diplopterys cabrerana. The drug is often present alongside its close analogues 5-MeO-DMT and bufotenin. It has widely been used as an entheogen or for shamanistic purposes in Central and South America, for instance among Amazonian peoples. This includes as the traditional beverage ayahuasca and other forms. Ayahuasca is boiled mixture of different plants, including a DMT-containing plant like Psychotria viridis, Psychotria carthagenensis, or Diplopterys cabrerana together with another plant known as Banisteriopsis caapi. A variety of different recipes may be used to make the brew. DMT is usually the main active constituent of ayahuasca, but ayahuasca is sometimes also brewed with plants that do not contain DMT. The drug is also found as a minor alkaloid in hallucinogenic snuffs such as those made from Virola or Anadenanthera plant materials but in which the major active drugs are instead 5-MeO-DMT and/or bufotenin. In addition to its use as an entheogen, DMT is widely used recreationally.DMT is not orally active on its own and is given by parenteral administration, such as smoking, intramuscular injection, subcutaneous injection, or intravenous injection. Other routes like intranasal, buccal, or rectal administration have also been tried but were all reported to be inactive. The lack of oral activity of DMT is due to rapid metabolism by the enzyme monoamine oxidase A. However, when taken in combination with an irreversible monoamine oxidase inhibitor or a reversible inhibitor of MAO-A such as a harmala alkaloid like harmine or harmaline or a pharmaceutical RIMA like moclobemide, DMT becomes orally active with an extended duration relative to parenteral use of DMT alone. Certain plants like Peganum harmala and the Banisteriopsis caapi used in ayahuasca contain harmala alkaloids which allow DMT to become orally active. When oral DMT is used with an MAOI and the materials are not naturally sourced, the combination is known as pharmahuasca. Changa is a plant-derived form of DMT that is smoked. Smoking and intravenous injection of DMT have extremely intense but very-short-lived effects, whereas intramuscular injection and particularly oral administration with an MAOI have less intense but longer-lasting effects.
File:N,N-DMT Freebase and Vape cartridge.jpg|thumb|left|200px|Free-base DMT powder extracted from Mimosa hostilis root bark ; vape cartridge made with free-base DMT extract.
In his book TiHKAL and other publications, Alexander Shulgin lists DMT's dose as greater than 350mg orally, 60 to 100mg by intramuscularly, subcutaneously, or via smoking, and 4 to 30mg by intravenous injection. He also reported that doses of 150 to 350mg or even up to 1,000mg orally and a dose of 100mg buccally produced no effects, whereas doses of 20 to 80mg intramuscularly, 30 to 100mg smoked, and 15 to 30mg intravenously were all active in producing effects. In terms of intramuscular injection, threshold effects occur at a dose of 30mg and full effects occur at a dose of 50 to 100mg by this route. Similarly, the dose for full effects with subcutaneous injection is likewise 60 to 100mg. With regard to intravenous injection, a dose of 4mg was indistinguishable from placebo, 8mg produced physical effects but no psychoactive effects, 15mg produced threshold psychedelic effects, and 30mg produced strong psychedelic effects. Shulgin lists the duration of parenteral DMT alone as up to 1hour.
In other more recent publications, different dose ranges of inhaled DMT of 2 to 100mg or 15 to 60mg have been described and typical doses have been reported to be 40 to 50mg. Concerning intravenous injection and based on contemporary clinical studies, 15mg has been described as a low dose, 25mg as an intermediate or "good effect" dose, and 30mg as a high or "ego-dissolution" dose. For intramuscular injection, a range of 50 to 100mg with an estimated typical dose of 75mg has been noted. The onset of DMT has been given as 10 to 15seconds smoked, within 2 to 5minutes intravenously, and within 2 to 5minutes intramuscularly. In addition, its duration is given as 5 to 20minutes via inhalation, less than 30minutes intravenously, and 30 to 60minutes intramuscularly.
DMT by continuous intravenous infusion has additionally been developed recently and can extend the duration of intravenous DMT to hours. The dose range for this route is 0.6 to 1.8mg per minute, with 0.6mg/minute being a low dose, 1.2mg/minute being an intermediate or "good effect" dose, and 1.8 to 2.4mg/minute being a high or "ego dissolution" dose. In addition to continuous intravenous infusion, DMT vape pens have been developed and distributed as an alternative to smoking.
Besides parenteral DMT alone, Shulgin also described the properties of oral DMT in combination with the MAOI and distinct ibogaine-like hallucinogen harmaline or in some cases Peganum harmala seeds in TiHKAL. This combination is a form of pharmahuasca and is similar to ayahuasca. Doses of 20 to 50mg harmaline with 55 to 60mg DMT both orally were associated with few to no effects. At higher harmaline doses, including 80 to 150mg, combined with 35 to 120mg DMT, both orally, clear MAOI activity occurred and more significant effects became apparent. More recent publications have defined the usually recommended doses as 50mg DMT and 100mg harmaline orally. Besides DMT with harmaline, the properties and effects of oral DMT in combination with harmine have also been studied by Jonathan Ott. He found that the threshold dose was 20 or 30mg DMT and 120mg harmine orally. Shulgin also reported in TiHKAL that 35 to 40mg DMT and 140 to 190mg harmine were unmistakeably active, whereas smaller doses of 30mg DMT and 120 to 140mg harmine orally were inactive. In notable contrast to harmaline, harmine does not have its own psychoactive effects when used at doses of up to at least 300mg orally. In pharmahuasca, the harmala alkaloid is usually taken first and then DMT is taken 15 to 20minutes later, although a shorter or longer interval may also be employed. The onset of oral DMT with an MAOI is within 1hour and its duration is 4 to 6hours.
Subjective effects
Subjective experiences of DMT indubitably includes profound time-dilatory, visual, auditory, tactile, and proprioceptive distortions and hallucinations, and other experiences that, by most firsthand accounts, defy verbal or visual description. Examples include perceiving hyperbolic geometry or seeing Escher-like impossible objects.Several scientific experimental studies have tried to measure subjective experiences of altered states of consciousness induced by drugs under highly controlled and safe conditions.
Rick Strassman and his colleagues conducted a five-year-long DMT study at the University of New Mexico in the 1990s. The results provided insight about the quality of subjective psychedelic experiences. In this study participants received the DMT dose via intravenous injection and the findings suggested that different psychedelic experiences can occur, depending on the dose. Lower doses produced some aesthetic and emotional responses, but not hallucinogenic experiences. In contrast, responses produced by higher doses researchers labeled as "hallucinogenic" that elicited "intensely colored, rapidly moving display of visual images, formed, abstract or both". Comparing to other sensory modalities, the most affected was the visual. Participants reported visual hallucinations, fewer auditory hallucinations and specific physical sensations progressing to a sense of bodily dissociation, as well as experiences of euphoria, calm, fear, and anxiety. These dose-dependent effects match well with anonymously posted "trip reports" online, where users report "breakthroughs" above certain doses.
Strassman also highlighted the importance of the context where the drug has been taken. He claimed that DMT has no beneficial effects of itself, rather the context when and where people take it plays an important role.
It appears that DMT can induce a state or feeling wherein the person believes they "communicate with other intelligent lifeforms". High doses of DMT produce a state that involves a sense of "another intelligence" that people sometimes describe as "super-intelligent", but "emotionally detached".
A 1995 study by Adolf Dittrich and Daniel Lamparter found that the DMT-induced altered state of consciousness is strongly influenced by habitual rather than situative factors. In the study, researchers used three dimensions of the APZ questionnaire to examine ASC. The first dimension, oceanic boundlessness, refers to dissolution of ego boundaries and is mostly associated with positive emotions. The second dimension, anxious ego-dissolution, represents a disordering of thoughts and decreases in autonomy and self-control. Last, visionary restructuralization refers to auditory/visual illusions and hallucinations. Results showed strong effects within the first and third dimensions for all conditions, especially with DMT, and suggested strong intrastability of elicited reactions independently of the condition for the OB and VR scales.
The effects of parenterally administered DMT have been described by Alexander Shulgin in his book TiHKAL. The perceptual effects included feeling strange, closed-eye imagery such as beautiful colored kaleidoscopic images, fast-moving geometric patterns, and complex and wonderful scenes alternating very rapidly, open-eye psychedelic visuals such as moving patterns, patterns becoming heads of animals, and peoples faces seeming to be masks, perceptual disturbances and distortions, yellowing of visual field, and rare auditory changes. Other effects included feeling intoxicated or stoned, everything feeling blurry, feeling a rush, time dilation, loss of spatial perception, ego dissolution, feeling as if one has died or no longer exists, feeling like one has no body, feeling that one is moving at the speed of light, feeling like one is gazing upon the entire universe, and encounters with strange entities or creatures. Emotional effects included emotional changes, euphoria, imagery being associated with deep emotional content and connotation, feeling overwhelmed, anxiety and fear, feeling like one can't breathe, a sense of dread and doom, and wanting one's mother. Physical side effects included pupil dilation, tingling, trembling, numbness, sweating, lightheadedness, athetosis, slight nausea, and increased heart rate and blood pressure.
In addition to parenteral DMT, Shulgin described the effects of oral DMT plus harmaline or in some cases Peganum harmala seeds in TiHKAL. The effects were reported to include closed-eye imagery such as colors, infinitely repeated and wavy sheets of patterns, and kaleidoscopic images, visual changes like brighter colors and patterns and distortions, music enhancement, time distortion, clarity, insights, intoxication, emotional changes, feeling alive and excited, depression, despair, and feeling psychotic. Other effects included difficulty focusing on thoughts, short-term memory disruption, feeling cold, nausea, gait impairment or difficulty walking, and an afterglow. The preceding effects are variably due to both DMT and harmaline, with harmaline also producing its own hallucinogenic effects at sufficiently doses, for instance 150mg or more.