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Dimethyltryptamine ( DMT), also known as N ,N -dimethyltryptamine (N, N-DMT), is a Psychedelic drug and investigational drug of the tryptamine family that natural product 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 (MAOI), such as the Ayahuasca of many native Amazonian tribes. DMT induces intense, often indescribable subjective experiences involving vivid visual hallucinations, altered Perception, Ego death, 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 analog and structural analog of other psychedelic tryptamines such as O-acetylpsilocin (4-AcO-DMT), psilocybin (4-PO-DMT), psilocin (4-HO-DMT), NB-DMT, O-methylbufotenin (5-MeO-DMT), and bufotenin (5-HO-DMT). Parts of the structure of DMT occur within some important biomolecules like serotonin and melatonin, making them structural analogs 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 scalability alternatives to longer-acting drugs like psilocybin for potential clinical use. DMT is currently undergoing for treatment-resistant depression.
The psychotropic effects of DMT were first studied scientifically by the Hungarian chemist and psychologist Stephen Szára, who performed research with volunteers in the mid-1950s. Szára, who later worked for the United States National Institutes of Health, researched DMT after his order to acquire LSD from the Swiss company Sandoz Laboratories was rejected on the grounds that the powerful psychotropic could be dangerous in the hands of a communist country. ()
DMT is generally not active orally unless it is combined with a monoamine oxidase inhibitor such as a reversible inhibitor of monoamine oxidase A (RIMA), for example, harmaline. Without a MAOI, the body quickly metabolizes orally administered DMT, and it therefore has no hallucinogenic effect unless the dose exceeds the body's monoamine oxidase's metabolic capacity. Other means of consumption such as vaporizing, injecting, or insufflating the drug can produce powerful hallucinations for a short time (usually less than half an hour), as the DMT reaches the brain before it can be metabolized by the body's natural monoamine oxidase. Taking an MAOI prior to vaporizing or injecting DMT prolongs and enhances the effects.
In 2023, a study investigated a novel method of DMT administration involving a bolus injection paired with a constant-rate infusion, with the goal of extending the DMT experience.
The dose range of DMT via bolus intravenous injection is 4 to 30mg. By constant infusion, the dose is 0.6 to 1.8mg per minute. (2025). 9783031121838 ISBN 9783031121838
Taken orally with an RIMA, DMT produces a long-lasting (over three hours), slow, deep metaphysical experience similar to that of psilocybin mushrooms, but more intense.
The intensity of orally administered DMT depends on the type and dose of MAOI administered alongside it. When ingested with 120 mg of harmine (a RIMA and member of the Harmala alkaloid), 20 mg of DMT was reported to have psychoactive effects by author and Ethnobotany Jonathan Ott. Ott reported that to produce a visionary state, the threshold oral dose was 30 mg DMT alongside 120 mg harmine. This is not necessarily indicative of a standard dose, as dose-dependent effects may vary due to individual variations in drug metabolism.
Without an MAOI, DMT is inactive orally at doses over 1,000mg.
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 dosage via intravenous injection and the findings suggested that different psychedelic experiences can occur, depending on the level of dosage. Lower doses (0.01 and 0.05 mg/kg) produced some aesthetic and emotional responses, but not hallucinogenic experiences (e.g., 0.05 mg/kg had mild mood elevating and calming properties). In contrast, responses produced by higher doses (0.2 and 0.4 mg/kg) 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 to "communicate with other intelligent lifeforms" (see "Entity encounters" below). 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 (ASC) 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 (OB), refers to ego death and is mostly associated with positive emotions. The second dimension, anxious ego-dissolution (AED), represents a disordering of thoughts and decreases in autonomy and self-control. Last, visionary restructuralization (VR) 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.
Strassman argues that the more positive of the "external entities" encountered in DMT experiences should be understood as analogous to certain forms of angels: Strassman's experimental participants also note that some other entities can subjectively resemble creatures more like insects and aliens. As a result, Strassman writes these experiences among his experimental participants "also left me feeling confused and concerned about where the spirit molecule was leading us. It was at this point that I began to wonder if I was getting in over my head with this research."
Hallucinations of strange creatures had been reported by Stephen Szara in a 1958 study in psychotic patients, in which he described how one of his subjects under the influence of DMT had experienced "strange creatures, dwarves or something" at the beginning of a DMT trip.
Other researchers of the entities seemingly encountered by DMT users describe them as "entities" or "beings" in humanoid as well as animal form, with descriptions of "little people" being common (non-human gnomes, elves, imps, etc.). Strassman and others have speculated that this form of hallucination may be the cause of alien abduction and extraterrestrial encounter experiences, which may occur through endogenously-occurring DMT.
Likening them to descriptions of rattling and chattering auditory phenomena described in encounters with the Hayyoth in the Book of Ezekiel, Rick Strassman notes that participants in his studies, when reporting encounters with the alleged entities, have also described loud auditory hallucinations, such as one subject reporting typically "the elves laughing or talking at high volume, chattering, twittering".
Chronic use of SSRIs, TCAs, and MAOIs diminish subjective effects of psychedelics due to presumed SSRI-induced 5-HT2A receptors downregulation and MAOI-induced 5-HT2A receptor desensitization. However, a clinical study of people with depression found that selective serotonin reuptake inhibitors (SSRIs) did not diminish the effects of DMT and instead resulted in greater mystical experience, emotional breakthrough, and ego dissolution scores with DMT than in people with depression not on . This was in contrast to previous research finding that SSRIs diminished the effects of serotonergic psychedelics. The interaction between psychedelics and and anticonvulsant are not well documented, however reports reveal that co-use of psychedelics with such as lithium may provoke seizure and dissociative effects in individuals with bipolar disorder.
DMT binds non-selectively with affinities below 0.6 μmol/L to the following serotonin receptors: 5-HT1A, 5-HT1B, 5-HT1D, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT6, and 5-HT7. An agonist action has been determined at 5-HT1A, 5-HT2A and 5-HT2C. Its efficacies at other serotonin receptors remain to be determined. Of special interest will be the determination of its efficacy at human 5-HT2B receptor as two in vitro assays evidenced DMT's high affinity for this receptor: 0.108 μmol/L and 0.184 μmol/L. This may be of importance because chronic or frequent uses of serotonergic drugs showing preferential high affinity and clear agonism at 5-HT2B receptor have been causally linked to valvular heart disease.
It has also been shown to possess affinity for the dopamine D1, α1-adrenergic, α2-adrenergic, imidazoline-1, and σ1 receptors. Converging lines of evidence established activation of the σ1 receptor at concentrations of 50-100 μmol/L. Its efficacies at the other receptor binding sites are unclear. It has also been shown in vitro to be a substrate for the cell-surface serotonin transporter (SERT) expressed in human platelets, and the rat vesicular monoamine transporter 2 (VMAT2), which was transiently expressed in fall armyworm Sf9 cells. DMT inhibited SERT-mediated serotonin uptake into platelets at an average concentration of 4.00 ± 0.70 μmol/L and VMAT2-mediated serotonin uptake at an average concentration of 93 ± 6.8 μmol/L. In addition, DMT is a potent serotonin releasing agent with an value of 81 to 114nM.
As with other so-called "classical hallucinogens", a large part of DMT psychedelic effects can be attributed to a functionally selective activation of the 5-HT2A receptor. DMT concentrations eliciting 50% of its maximal effect (half maximal effective concentration = EC50) at the human 5-HT2A receptor in vitro are in the 0.118-0.983 μmol/L range. This range of values coincides well with the range of concentrations measured in blood and plasma after administration of a fully psychedelic dose (see Pharmacokinetics).
DMT is one of the only psychedelics that isn't known to produce tolerance to its hallucinogenic effects. The lack of tolerance with DMT may be related to the fact that, unlike other psychedelics such as LSD and DOI, DMT does not desensitize serotonin 5-HT2A receptors in vitro. This may be due to the fact that DMT is a biased agonist of the serotonin 5-HT2A receptor. More specifically, DMT activates the Gq protein cell signaling of the serotonin 5-HT2A receptor without significantly recruiting β-arrestin2. Activation of β-arrestin2 is linked to receptor downregulation and tachyphylaxis. Similarly to DMT, 5-MeO-DMT is a biased agonist of the serotonin 5-HT2A receptor, with minimal β-arrestin2 recruitment, and likewise has been associated with little tolerance to its hallucinogenic effects. On the other hand, the lack of apparent tolerance of DMT and similar agents may simply be related to their very short durations. (1977). 9783642667114, Springer Berlin Heidelberg. ISBN 9783642667114
As DMT has been shown to have slightly better efficacy (EC50) at human serotonin 2C receptor than at the 2A receptor, 5-HT2C is also likely implicated in DMT's overall effects. Other receptors such as 5-HT1A and σ1 may also play a role.
In 2009, it was hypothesized that DMT may be an endogenous ligand for the σ1 receptor. The concentration of DMT needed for σ1 activation in vitro (50-100 μmol/L) is similar to the behaviorally active concentration measured in mouse brain of approximately 106 μmol/L This is minimally 4 orders of magnitude higher than the average concentrations measured in rat brain tissue or human plasma under basal conditions (see Endogenous DMT), so σ1 receptors are likely to be activated only under conditions of high local DMT concentrations. If DMT is stored in synaptic vesicles, such concentrations might occur during vesicular release. To illustrate, while the average concentration of serotonin in brain tissue is in the 1.5-4 μmol/L range, the concentration of serotonin in synaptic vesicles was measured at 270 mM. Following vesicular release, the resulting concentration of serotonin in the synaptic cleft, to which serotonin receptors are exposed, is estimated to be about 300 μmol/L. Thus, while in vitro receptor binding affinities, efficacies, and average concentrations in tissue or plasma are useful, they are not likely to predict DMT concentrations in the vesicles or at synaptic or intracellular receptors. Under these conditions, notions of receptor selectivity are moot, and it seems probable that most of the receptors identified as targets for DMT (see above) participate in producing its psychedelic effects.
In September 2020, an in vitro and in vivo study found that DMT present in the ayahuasca infusion promotes neurogenesis, meaning it helps with generating Neuron.
DMT produces the head-twitch response (HTR), a behavioral proxy of psychedelic drug-like effects, in rodents. However, its effects in the HTR paradigm in mice that are highly strain-dependent, including producing an HTR comparable to other psychedelics, producing an HTR that is much weaker than that of other psychedelics, or producing no HTR at all. These conflicting results may be due to rapid metabolism of DMT and/or other peculiarities of DMT in different species. Besides the HTR, DMT also substitutes for LSD and DOM in rodent drug discrimination tests.
DMT has been found to be a psychoplastogen, a compound capable of promoting rapid and sustained neuroplasticity that may have wide-ranging therapeutic benefit.
The cryo-EM structures of the serotonin 5-HT2A receptor with DMT, as well as with various other psychedelics and serotonin 5-HT2A receptor agonists, have been solved and published by Bryan L. Roth and colleagues.
DMT peak level concentrations ( Cmax) measured in the blood after intramuscular (IM) injection (0.7 mg/kg, n = 11) and in plasma following intravenous (IV) administration (0.4 mg/kg, n = 10) of fully psychedelic doses are in the range of around 14 to 154 μg/L and 32 to 204 μg/L, respectively. The corresponding molar concentrations of DMT are therefore in the range of 0.074-0.818 μmol/L in whole blood and 0.170-1.08 μmol in plasma. However, several studies have described active transport and accumulation of DMT into rat and dog brains following peripheral administration. Similar active transport and accumulation processes likely occur in human brains and may concentrate DMT in brain by several-fold or more (relatively to blood), resulting in local concentrations in the micromolar or higher range. Such concentrations would be commensurate with serotonin brain tissue concentrations, which have been consistently determined to be in the 1.5-4 μmol/L range.
DMT easily crosses the blood-brain barrier. Studies on the llipophilicity of DMT have been contradictory -- most studies find DMT to be either lipophilic or slightly lipophilic, but a 2023 study found it to be lipophobic.
DMT is primarily metabolized by monoamine oxidase A (MAO-A) into indole-3-acetic acid and to a much lesser extent in the liver by CYP2D6 and CYP2C19. When taken orally it is metabolized by MAO-A in the liver and gut, and is thus not orally bioavailable unless a monoamine oxidase inhibitor is taken (as is naturally found in the ayahuasca brew). When taken intravenously, DMT is primarily metabolized MAO-A in the circulatory system and brain. When smoked, a more substantial fraction (possibly as high as 10-20%) is metabolized in the liver by CYP2D6 and CYP2C19.
Detailed pharmacokinetic analyses for inhaling or vaporizing DMT appear to be lacking.
DMT is a lipophilic compound, with an experimental log P of 2.57.
Alternatively, an excess of methyl iodide or methyl p-toluenesulfonate and sodium carbonate can be used to over-methylate tryptamine, resulting in the creation of a quaternary ammonium salt, which is then dequaternized (demethylated) in ethanolamine to yield DMT. The same two-step procedure is used to synthesize other N, N-dimethylated compounds, such as 5-MeO-DMT.
Alternatively, an acid-base extraction is sometimes used instead.
A variety of plants contain DMT at sufficient levels for being viable sources, but specific plants such as Mimosa tenuiflora, Acacia acuminata, and Acacia confusa are most often used.
The chemicals involved in the extraction are commonly available. The plant-material may be illegal to procure in some countries. The end-product (DMT) is illegal in most countries.
Selectivity rather than sensitivity proved to be a challenge for some TLC methods with the discovery in 1974-1975 that incubating rat blood cells or brain tissue with (14C-CH3)SAM and NMT as substrate mostly yields tetrahydro-β-carboline derivatives, and negligible amounts of DMT in brain tissue. It is indeed simultaneously realized that the TLC methods used thus far in almost all published studies on INMT and DMT biosynthesis are incapable to resolve DMT from those tetrahydro-β-carbolines. These findings are a blow for all previous claims of evidence of INMT activity and DMT biosynthesis in avian and mammalian brain, including in vivo, as they all relied upon use of the problematic TLC methods: their validity is doubted in replication studies that make use of improved TLC methods, and fail to evidence DMT-producing INMT activity in rat and human brain tissues. Published in 1978, the last study attempting to evidence in vivo INMT activity and DMT production in brain (rat) with TLC methods finds biotransformation of radiolabeled tryptamine into DMT to be real but "insignificant". Capability of the method used in this latter study to resolve DMT from tetrahydro-β-carbolines is questioned later.
To localize INMT, a qualitative leap is accomplished with use of modern techniques of molecular biology, and of immunohistochemistry. In humans, a gene encoding INMT is determined to be located on chromosome 7. Northern blot reveal INMT messenger RNA (mRNA) to be highly expressed in rabbit lung, and in human thyroid, adrenal gland, and lung. Intermediate levels of expression are found in human heart, skeletal muscle, trachea, stomach, small intestine, pancreas, testis, prostate, placenta, lymph node, and spinal cord. Low to very low levels of expression are noted in rabbit brain, and human thymus, liver, spleen, kidney, colon, ovary, and bone marrow. INMT mRNA expression is absent in human peripheral blood leukocytes, whole brain, and in tissue from seven specific brain regions (thalamus, subthalamic nucleus, caudate nucleus, hippocampus, amygdala, substantia nigra, and corpus callosum). Immunohistochemistry showed INMT to be present in large amounts in Goblet cell of small and large intestines. In 2011, immunohistochemistry revealed the presence of INMT in primate nervous tissue including retina, spinal cord motor neurons, and pineal gland. A 2020 study using in-situ hybridization, a far more accurate tool than the northern blot analysis, found mRNA coding for INMT expressed in the human cerebral cortex, choroid plexus, and pineal gland.
In 2013, researchers reported DMT in the pineal gland microdialysis of rodents.
A study published in 2014 reported the biosynthesis of N, N-dimethyltryptamine (DMT) in the human melanoma cell line SK-Mel-147 including details on its metabolism by peroxidases.
It is assumed that more than half of the amount of DMT produced by the acidophilic cells of the pineal gland is secreted before and during death, the amount being 2.5-3.4 mg/kg. However, this claim by Strassman has been criticized by David Nichols who notes that DMT does not appear to be produced in any meaningful amount by the pineal gland. Removal or calcification of the pineal gland does not induce any of the symptoms caused by removal of DMT. The symptoms presented are consistent solely with reduction in melatonin, which is the pineal gland's known function. Nichols instead suggests that dynorphin and other endorphins are responsible for the reported euphoria experienced by patients during a near-death experience.
In 2014, researchers demonstrated the Immunomodulation potential of DMT and 5-MeO-DMT through the Sigma-1 receptor of human immune cells. This immunomodulatory activity may contribute to significant anti-inflammatory effects and tissue regeneration.
The first claimed detection of endogenous DMT in mammals was published in June 1965: German researchers F. Franzen and H. Gross report to have evidenced and quantified DMT, along with its structural analog bufotenin (5-HO-DMT), in human blood and urine. In an article published four months later, the method used in their study was strongly criticized, and the credibility of their results challenged.
Few of the analytical methods used prior to 2001 to measure levels of endogenously formed DMT had enough sensitivity and selectivity to produce reliable results. Gas chromatography, preferably coupled to mass spectrometry (GC-MS), is considered a minimum requirement. A study published in 2005 implements the most sensitive and selective method ever used to measure endogenous DMT: liquid chromatography-tandem mass spectrometry with electrospray ionization (LC-ESI-MS/MS) allows for reaching limits of detection (LODs) 12 to 200 fold lower than those attained by the best methods employed in the 1970s. The data summarized in the table below are from studies conforming to the abovementioned requirements (abbreviations used: CSF = cerebrospinal fluid; LOD = limit of detection; n = number of samples; ng/L and ng/kg = nanograms (10−9 g) per litre, and nanograms per kilogram, respectively):
| DMT in body fluids and tissues (NB: units have been harmonized) ! style="background:azure; vertical-align:middle; text-align:center; width:30px;" | Species ! style="background:azure; vertical-align:middle; text-align:center; width:60px;" | Sample ! style="background:azure; vertical-align:middle; text-align:center; width:400px;" | Results |
| Blood plasma | < LOD ( n = 71) ♦ < LOD ( n = 38); 1,000 & 10,600ng/L ( n = 2) | ||
| Whole blood | < LOD ( n = 20); 50-790ng/L ( n = 20) | ||
| Urine | < 100ng/L ( n = 9) ♦ < LOD ( n = 60); 160-540ng/L ( n = 5) ♦ Detected in n = 10 by GC-MS | ||
| Feces | < 50ng/kg (n = 12); 130ng/kg ( n = 1) | ||
| Kidney | 15ng/kg ( n = 1) | ||
| Lung | 14ng/kg ( n = 1) | ||
| Lumbar puncture CSF | 100,370ng/L ( n = 1); 2,330-7,210ng/L ( n = 3); 350 & 850ng/L ( n = 2) | ||
| Lung | 22 & 12ng/kg ( n = 2) | ||
| Liver | 6 & 10ng/kg ( n = 2) | ||
| Brain | 10 & 15ng/kg ( n = 2) ♦ Measured in Synaptic vesicle Fractionation | ||
A 2013 study found DMT in Microdialysis obtained from a rat's pineal gland, providing evidence of endogenous DMT in the mammalian brain. In 2019 experiments showed that the rat brain is capable of synthesizing and releasing DMT. These results raise the possibility that this phenomenon may occur similarly in human brains.
Quantities of dimethyltryptamine and O-methylbufotenin were found present in the cerebrospinal fluid of humans in a 1978 psychiatric study.
This transmethylation mechanism has been repeatedly and consistently proven by Isotope labeling of SAM methyl group with carbon-14 ((14C-CH3)SAM).
DMT was first synthesized in 1931 by Canadian chemist Richard Helmuth Fredrick Manske. In general, its discovery as a natural product is credited to Brazilian chemist and microbiologist Oswaldo Gonçalves de Lima, who isolated an alkaloid he named nigerina (nigerine) from the root bark of Mimosa tenuiflora in 1946. (1996). 9780961423490, Natural Products. ISBN 9780961423490 However, in a careful review of the case Jonathan Ott shows that the empirical formula for nigerine determined by Gonçalves de Lima, which notably contains an atom of oxygen, can match only a partial, "impure" or "contaminated" form of DMT. (1998). 9783861350330, VWB. ISBN 9783861350330 It was only in 1959, when Gonçalves de Lima provided American chemists a sample of Mimosa tenuiflora roots, that DMT was unequivocally identified in this plant material. Less ambiguous is the case of isolation and formal identification of DMT in 1955 in seeds and pods of Anadenanthera peregrina by a team of American chemists led by Evan Horning (1916-1993). Since 1955, DMT has been found in a number of organisms: in at least fifty plant species belonging to ten families, (1994). 9780961423452, Natural Products. ISBN 9780961423452 and in at least four animal species, including one gorgonian and three mammalian species (including humans).
In terms of a scientific understanding, the effects of DMT were not uncovered until 1956 by Hungarian chemist and psychiatrist Stephen Szara. In his paper Dimethyltryptamin: Its Metabolism in Man; the Relation of its Psychotic Effect to the Serotonin Metabolism, Szara employed synthetic DMT, synthesized by the method of Speeter and Anthony, which was then administered to 20 volunteers by intramuscular injection. Urine samples were collected from these volunteers for the identification of DMT metabolites. This is considered to be the converging link between the chemical structure DMT to its cultural consumption as a psychoactive and religious sacrament.
Another historical milestone is the discovery of DMT in plants frequently used by Amazonian natives as additive to the vine Banisteriopsis caapi to make ayahuasca decoctions. In 1957, American chemists Francis Hochstein and Anita Paradies identified DMT in an "aqueous extract" of leaves of a plant they named Prestonia amazonicum sic and described as "commonly mixed" with B. caapi. The lack of a proper botanical identification of Prestonia amazonica in this study led American ethnobotany Richard Evans Schultes (1915-2001) and other scientists to raise serious doubts about the claimed plant identity. The mistake likely led the writer William Burroughs to regard the DMT he experimented with in Tangier in 1961 as "Prestonia". (2025). 9781583947326, North Atlantic Books / Evolver. ISBN 9781583947326 Better evidence was produced in 1965 by French pharmacologist Jacques Poisson, who isolated DMT as a sole alkaloid from leaves, provided and used by Aguaruna people Indians, identified as having come from the vine Diplopterys cabrerana (then known as Banisteriopsis rusbyana). Published in 1970, the first identification of DMT in the plant Psychotria viridis, another common additive of ayahuasca, was made by a team of American researchers led by pharmacologist Ara der Marderosian. Not only did they detect DMT in leaves of P. viridis obtained from Kaxinawá indigenous people, but they also were the first to identify it in a sample of an ayahuasca decoction, prepared by the same indigenous people.
In December 2004, the U.S. Supreme Court lifted a stay allowing the Brazil-based União do Vegetal church to use a decoction containing DMT in their Christmas services that year. This decoction is a tea made from boiled leaves and vines, known as hoasca within the UDV, and ayahuasca in different cultures. In Gonzales v. O Centro Espírita Beneficente União do Vegetal, the Supreme Court heard arguments on November 1, 2005, and unanimously ruled in February 2006 that the U.S. federal government must allow the UDV to import and consume the tea for religious ceremonies under the 1993 Religious Freedom Restoration Act.
Also suing under the Religious Freedom Restoration Act, three Santo Daime churches filed suit in federal court to gain legal status to import DMT-containing ayahuasca tea in 2008. The U.S. District Court in Oregon ruled in Church of the Holy Light of the Queen v. Mukasey (615 F.Supp.2d 1210) ruled that the religious group could import, distribute, and brew ayahuasca. A matter of religious freedom protected by the religious freedom law, the court issued a Injunction barring the government from prohibiting or penalizing the sacramental use of the religious drink.
Akasha Song previously manufactured and sold DMT on the dark web and is said to have been the largest DMT producer and seller in history.
A recent Phase 1/2 clinical trial evaluated the safety, tolerability, pharmacokinetics, and antidepressant effects of SPL026, an intravenous formulation of DMT Fumaric acid, in both healthy volunteers and patients with moderate-to-severe major depressive disorder, using randomized, placebo-controlled and open-label dosing protocols. It found that inhaled 5-MeO-DMT (GH001) was well tolerated and produced rapid antidepressant effects in treatment-resistant depression, with individualized dosing showing the highest remission rates.
A Phase 1 open-label study assessed the safety, tolerability, pharmacokinetics, and preliminary efficacy of intravenous SPL026 alone or combined with SSRIs in patients with major depressive disorder whose symptoms were not fully relieved by SSRIs.
In a phase 2a open-label trial, inhaled DMT produced rapid, well-tolerated, and sustained antidepressant effects in patients with treatment-resistant depression, showing high response and remission rates within 7 days and lasting up to 3 months.
A single-day, open-label trial found that vaporized DMT produced rapid and sustained antidepressant effects in treatment-resistant depression, with up to 50% of participants maintaining remission one month post-dose.
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