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[h=1]Dimethyltryptamine[/h]From Wikipedia, the free encyclopedia
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DimethyltryptamineN,N-Dimethyltryptamine (DMT) is a naturally occurring psychedelic compound of the tryptamine family. DMT is ubiquitously found in plants[SUP][3][/SUP] and also in trace amounts in mammals, including humans, where it may putatively function as a trace amine neurotransmitter[SUP][4][/SUP]. It is originally derived from the essential amino acid tryptophan and ultimately produced by the enzyme INMT during normal metabolism.[SUP][5][/SUP] The natural significance of its widespread presence remains undetermined. Structurally, DMT is analogous to the neurotransmitter serotonin (5-HT), the hormone melatonin, and other psychedelic tryptamines, such as 5-MeO-DMT, bufotenin, and psilocin (the active metabolite of psilocybin).
In some cultures DMT is ingested as a psychedelic drug (in either extracted or synthesized forms).[SUP][6][/SUP] When DMT is inhaled or consumed, depending on the dose, its subjective effects can range from short-lived milder psychedelic states to powerful immersive experiences, which include a total loss of connection to conventional reality, which may be so extreme that it becomes ineffable.[SUP][7][/SUP] DMT is also the primary psychoactive in ayahuasca, an Amazonian Amerindian brew employed for divinatory and healing purposes. Pharmacologically, ayahuasca combines DMT with an MAOI, an enzyme inhibitor that allows DMT to be orally active.[SUP][8][/SUP]
[h=2][edit] History[/h]DMT was first synthesized in 1931 by Canadian chemist Richard Manske (1901–1977).[SUP][9][/SUP][SUP][10][/SUP] Its discovery as a natural product is generally credited to Brazilian chemist and microbiologist Oswaldo Gonçalves de Lima (1908–1989) who, in 1946, isolated an alkaloid he named nigerina (nigerine) from the root bark of jurema preta, that is, Mimosa tenuiflora.[SUP][10][/SUP][SUP][11][/SUP][SUP][12][/SUP] 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 only match a partial, "impure" or "contaminated" form of DMT.[SUP][13][/SUP] 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.[SUP][13][/SUP][SUP][14][/SUP] 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).[SUP][13][/SUP][SUP][15][/SUP] Since 1955 DMT has been found in a host of organisms: in at least 50 plant species belonging to 10 families,[SUP][3][/SUP] and in at least 4 animal species, including one gorgonian[SUP][16][/SUP] and 3 mammalian species (see Endogenous DMT).
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 identify DMT in an "aqueous extract" of leaves of a plant they name Prestonia amazonicum (sic) and describe as "commonly mixed" with B. caapi.[SUP][17][/SUP] The lack of a proper botanical identification of Prestonia amazonica in this study led American ethnobotanist Richard Evans Schultes (1915–2001) and other scientists to raise serious doubts about the claimed plant identity.[SUP][18][/SUP][SUP][19][/SUP] A better evidence is produced in 1965 by French pharmacologist Jacques Poisson who isolates DMT as sole alkaloid from leaves, provided and used by Aguaruna Indians, identified as pertaining to the vine Diplopterys cabrerana (then known as Banisteriopsis rusbyana).[SUP][19][/SUP] Published in 1970, the first identification of DMT in the other commonly used additive plant Psychotria viridis[SUP][11][/SUP] was made by a team of American researchers led by pharmacologist Ara der Marderosian.[SUP][20][/SUP] Not only did they detect DMT in leaves of P. viridis obtained from Cashinahua Indians, but they also were the first to identify it in a sample of an ayahuasca decoction, prepared by the same Indians.[SUP][11][/SUP]
[h=2][edit] Biosynthesis[/h]
Biosynthetic pathway for N,N-dimethyltryptamine
Dimethyltryptamine is an indole alkaloid derived from the shikimate pathway. Its biosynthesis is relatively simple and summarized in the picture to the left. In plants, the parent amino acid L-tryptophan is produced endogenously where in animals L-tryptophan is an essential amino acid coming from diet. No matter the source of L-tryptophan, the biosynthesis begins with its decarboxylation by an aromatic amino acid decarboxylase (AADC) enzyme (step 1). The resulting decarboxylated tryptophan analog is tryptamine. Tryptamine then undergoes a transmethylation (step 2): the enzyme indolethylamine-N-methyltransferase (INMT) catalyzes the transfer of a methyl group from cofactor S-adenosyl-methionine (SAM), via nucleophilic attack, to tryptamine. This reaction transforms SAM into S-adenosylhomocysteine (SAH), and gives the intermediate product N-methyltryptamine (NMT).[SUP][21][/SUP][SUP][22][/SUP] NMT is in turn transmethylated by the same process (step 3) to form the end product N,N-dimethyltryptamine. Tryptamine transmethylation is regulated by two products of the reaction: SAH,[SUP][5][/SUP][SUP][23][/SUP][SUP][24][/SUP] and DMT[SUP][5][/SUP][SUP][24][/SUP] were shown ex vivo to be among the most potent inhibitors of rabbit INMT activity.
This transmethylation mechanism has been repeatedly and consistently proven by radiolabeling of SAM methyl group with carbon-14 ([SUP]14[/SUP]C-CH[SUB]3[/SUB])SAM).[SUP][5][/SUP][SUP][21][/SUP][SUP][24][/SUP][SUP][25][/SUP][SUP][26][/SUP]
[h=3][edit] Evidence in mammals[/h]Published in Science in 1961, Julius Axelrod found an N-methyltransferase enzyme capable of mediating biotransformation of tryptamine into DMT in a rabbit's lung.[SUP][21][/SUP]This finding initiated a still ongoing scientific interest in endogenous DMT production in humans and other mammals.[SUP][22][/SUP][SUP][27][/SUP]From then on, two major complementary lines of evidence have been investigated: localization and further characterization of the N-methyltransferase enzyme, and analytical studies looking for endogenously produced DMT in body fluids and tissues.[SUP][22][/SUP]
[h=4][edit] INMT[/h]Before techniques of molecular biology were used to localize indolethylamine N-methyltransferase (INMT),[SUP][24][/SUP][SUP][26][/SUP] characterization and localization went on a par: samples of the biological material where INMT is hypothesized to be active are subject to enzyme assay. Those enzyme assays are performed either with a radiolabeled methyl donor like ([SUP]14[/SUP]C-CH[SUB]3[/SUB])SAM to which known amounts of unlabeled substrates like tryptamine are added,[SUP][22][/SUP] or with addition of a radiolabeled substrate like ([SUP]14[/SUP]C)NMT to demonstrate in vivo formation.[SUP][5][/SUP][SUP][25][/SUP] As qualitative determination of the radioactively tagged product of the enzymatic reaction is sufficient to characterize INMT existence and activity (or lack of), analytical methods used in INMT assays don't require to be as sensitive as those needed to directly detect and quantify the minute amounts of endogenously formed DMT (see DMT subsection below). The essentially qualitative method thin layer chromatography (TLC) was thus used in a vast majority of studies.[SUP][22][/SUP] Also, robust evidence that INMT can catalyze transmethylation of tryptamine into NMT and DMT could be provided with reverse isotope dilution analysis coupled to mass spectrometry for rabbit[SUP][28][/SUP][SUP][29][/SUP] and human[SUP][30][/SUP] lung during the early 1970s.
Selectivity rather than sensitivity proved to be an Achilles’ heel for some TLC methods with the discovery in 1974-1975 that incubating rat blood cells or brain tissue with ([SUP]14[/SUP]C-CH[SUB]3[/SUB])SAM and NMT as substrate mostly yields tetrahydro-β-carboline derivatives,[SUP][5][/SUP][SUP][22][/SUP][SUP][31][/SUP] and negligible amounts of DMT in brain tissue.[SUP][22][/SUP] 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.[SUP][22][/SUP] These findings are a blow for all previous claims of evidence of INMT activity and DMT biosynthesis in avian[SUP][32][/SUP] and mammalian brain,[SUP][33][/SUP][SUP][34][/SUP] including in vivo,[SUP][35][/SUP][SUP][36][/SUP] as they all relied upon use of the problematic TLC methods[SUP][22][/SUP]: 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.[SUP][37][/SUP][SUP][38][/SUP] 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".[SUP][39][/SUP] Capability of the method used in this latter study to resolve DMT from tetrahydro-β-carbolines is questioned later.[SUP][5][/SUP]
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.[SUP][26][/SUP] Northern blot analyses reveal INMT messenger RNA (mRNA) to be highly expressed in rabbit lung,[SUP][24][/SUP] and in human thyroid, adrenal gland, and lung.[SUP][26][/SUP][SUP][40][/SUP] Intermediate levels of expression are found in human heart, skeletal muscle, trachea, stomach, small intestine, pancreas, testis, prostate, placenta, lymph node, and spinal cord.[SUP][26][/SUP][SUP][40][/SUP] Low to very low levels of expression are noted in rabbit brain,[SUP][26][/SUP] and human thymus, liver, spleen, kidney, colon, ovary, and bone marrow.[SUP][26][/SUP][SUP][40][/SUP] INMT mRNA expression is absent in human peripheral blood leukocytes, whole brain, and in tissue from 7 specific brain regions (thalamus, subthalamic nucleus, caudate nucleus, hippocampus, amygdala, substantia nigra, and corpus callosum).[SUP][26][/SUP][SUP][40][/SUP] Immunohistochemistry showed INMT to be present in large amounts in glandular epithelial cells of small and large intestines, and to be absent in neurons.[SUP][27][/SUP]
[h=4][edit] Endogenous DMT[/h]The first claimed detection of mammalian endogenous DMT 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-OH-DMT), in human blood and urine.[SUP][41][/SUP] In an article published four months later, the method used in their study is strongly criticized, and credibility of their results challenged.[SUP][42][/SUP]
In 2001, surveys, made in research articles, point that few of the analytical methods previously used to measure levels of endogenously formed DMT had enough sensitivity and selectivity to produce reliable results.[SUP][43][/SUP][SUP][44][/SUP] Gas chromatography, preferably coupled to mass spectrometry (GC-MS), is considered a minimum requirement.[SUP][44][/SUP] A study published in 2005[SUP][27][/SUP] implements the most sensitive and selective method ever used to measure endogenous DMT[SUP][45][/SUP]: liquid chromatography-tandem mass spectrometry with electrospray ionization (LC-ESI-MS/MS) allows to reach limits of detection (LODs) 12 to 200 fold lower (that is, better) 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[SUP]−9[/SUP] g) per litre, and nanograms per kilogram, respectively):
DMT
in body fluids and tissues
(NB: units have been harmonized)[h=2][edit] Physical and chemical properties[/h]
DMT Crystals
DMT is commonly handled and stored as a fumarate as other DMT acid salts are generally very hygroscopic and will not readily crystallize. Its freebase form, although less stable than DMT fumarate, is favored by recreational users choosing to vaporize the chemical because it has a lower boiling point. In contrast to DMT's base, its salts are water-soluble. DMT in solution degrades relatively quickly and should be stored protected from air, light, and heat in a freezer.
[h=2][edit] Pharmacology[/h][h=3][edit] Pharmacokinetics[/h]DMT peak levels concentrations (C[SUB]max[/SUB]) measured in whole blood after intramuscular (IM) injection (0.7 mg/kg, n = 11)[SUP][51][/SUP] and in plasma following intravenous (IV) administration (0.4 mg/kg, n = 10)[SUP][52][/SUP] of fully psychedelic doses are in the range of ≈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 µM in whole blood and 0.170–1.08 µM in plasma. However, several studies have described active transport and accumulation of DMT into rat and dog brain following peripheral administration.[SUP][53][/SUP][SUP][54][/SUP][SUP][55][/SUP][SUP][56][/SUP][SUP][57][/SUP] Similar active transport, and accumulation processes likely occur in human brain 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 μM range.[SUP][58][/SUP][SUP][59][/SUP]
Closely coextending with peak psychedelic effects, mean time to reach peak concentrations (T[SUB]max[/SUB]) was determined to be 10–15 minutes in whole blood after IM injection,[SUP][51][/SUP] and 2 minutes in plasma after IV administration.[SUP][52][/SUP] When taken orally mixed in an ayahuasca decoction, and in freeze-dried ayahuasca gel caps, DMT T[SUB]max[/SUB] is considerably delayed: 107.59 ± 32.5 minutes,[SUP][60][/SUP] and 90–120 minutes,[SUP][61][/SUP] respectively. The pharmacokinetics for smoking DMT have not been studied or reported.
[h=3][edit] Pharmacodynamics[/h]DMT binds non-selectively with affinities < 0.6 μM to the following serotonin receptors: 5-HT[SUB]1A[/SUB],[SUP][62][/SUP][SUP][63][/SUP][SUP][64][/SUP] 5-HT[SUB]1B[/SUB],[SUP][62][/SUP][SUP][65][/SUP] 5-HT[SUB]1D[/SUB],[SUP][62][/SUP][SUP][64][/SUP][SUP][65][/SUP] 5-HT[SUB]2A[/SUB],[SUP][62][/SUP][SUP][64][/SUP][SUP][65][/SUP][SUP][66][/SUP] 5-HT[SUB]2B[/SUB],[SUP][62][/SUP][SUP][65][/SUP] 5-HT[SUB]2C[/SUB],[SUP][62][/SUP][SUP][65][/SUP][SUP][66][/SUP] 5-HT6,[SUP][62][/SUP][SUP][65][/SUP] and 5-HT7.[SUP][62][/SUP][SUP][65][/SUP] An agonist action has been determined at 5-HT[SUB]1A[/SUB],[SUP][63][/SUP] 5-HT[SUB]2A[/SUB] and 5-HT[SUB]2C[/SUB].[SUP][62][/SUP][SUP][65][/SUP][SUP][66][/SUP] Its efficacies at other serotonin receptors remain to be determined. Of special interest will be the determination of its efficacy at human 5-HT[SUB]2B[/SUB] receptor as two in vitro assays evidenced DMT high affinity for this receptor: 0.108 μM[SUP][65][/SUP] and 0.184 μM.[SUP][62][/SUP] This may be of importance because chronic or frequent uses of serotonergic drugs showing preferential high affinity and clear agonism at 5-HT[SUB]2B[/SUB] receptor have been causally linked to valvular heart disease.[SUP][67][/SUP][SUP][68][/SUP]
It has also been shown to possess affinity for the dopamine D[SUB]1[/SUB], α[SUB]1[/SUB]-adrenergic, α[SUB]2[/SUB]-adrenergic, imidazoline-1, sigma-1 (σ[SUB]1[/SUB]), and trace amine-associated receptors.[SUP][64][/SUP][SUP][65][/SUP][SUP][69][/SUP] Agonism was demonstrated at 1 μM at the rat trace amine-associated receptor 1 (TAAR1)[SUP][70][/SUP] and converging lines of evidence established activation of the σ[SUB]1[/SUB] receptor at concentrations of 50-100 μM.[SUP][71][/SUP] 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) and the intracellular vesicular monoamine transporter 2 (VMAT2), inhibiting SERT-mediated serotonin uptake in human platelets at an average concentration of 4.00 ± 0.70 μM and VMAT2-mediated serotonin uptake in vesicles (of army worm Sf9 cells) expressing rat VMAT-2 at an average concentration of 93 ± 6.8 μM.[SUP][72][/SUP]
Like with other so-called "classical hallucinogens",[SUP][73][/SUP] a large part of DMT psychedelic effects can be attributed to a specific activation of the 5-HT[SUB]2A[/SUB] receptor.[SUP][52][/SUP][SUP][62][/SUP][SUP][74][/SUP][SUP][75][/SUP][SUP][76][/SUP][SUP][77][/SUP][SUP][78][/SUP] DMT concentrations eliciting 50% of its maximal effect (half maximal effective concentration = EC[SUB]50[/SUB] or K[SUB]act[/SUB]) at the human 5-HT[SUB]2A[/SUB] receptor in vitro are in the 0.118-0.983 μM range.[SUP][62][/SUP][SUP][65][/SUP][SUP][66][/SUP][SUP][79][/SUP] 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).
As DMT has been shown to have slightly better efficacy (EC[SUB]50[/SUB]) at human serotonin 2C receptor than at 2A receptor,[SUP][65][/SUP][SUP][66][/SUP] 5-HT[SUB]2C[/SUB] highly likely also is implicated in DMT overall effects.[SUP][75][/SUP][SUP][80][/SUP] Other receptors, such as 5-HT[SUB]1A[/SUB][SUP][64][/SUP][SUP][75][/SUP][SUP][77][/SUP] σ[SUB]1[/SUB],[SUP][71][/SUP][SUP][81][/SUP] and TAAR1[SUP][70][/SUP][SUP][82][/SUP][SUP][83][/SUP] may also play a role.
In 2009 it was hypothesized that DMT may be an endogenous ligand for the σ[SUB]1[/SUB] receptor.[SUP][71][/SUP][SUP][81][/SUP] The concentration of DMT needed for σ[SUB]1[/SUB] activation in vitro (50-100 μM) is similar to the behaviorally active concentration measured in mouse brain of approximately 106 μM [SUP][84][/SUP] This is minimally 4 orders of magnitude (10[SUP]4[/SUP]) higher than the average concentrations measured in rat brain tissue or human plasma under basal conditions (see Endogenous DMT), so σ[SUB]1[/SUB] receptors are likely to be activated only under conditions of high local DMT concentrations. If DMT is stored in synaptic vesicles,[SUP][72][/SUP] such concentrations might occur during vesicular release. To illustrate, while the average concentration of serotonin in brain tissue is in the 1.5-4 μM range,[SUP][58][/SUP][SUP][59][/SUP] the concentration of serotonin in synaptic vesicles was measured at 270 mM.[SUP][85][/SUP] Following vesicular release, the resulting concentration of serotonin in the synaptic cleft, to which serotonin receptors are exposed, is estimated to be about 300 μM. 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.
[h=2][edit] Psychedelic properties[/h]DMT occurs naturally in many species of plants often in conjunction with its close chemical relatives 5-MeO-DMT and bufotenin (5-OH-DMT).[SUP][86][/SUP] DMT-containing plants are commonly used in South American Shamanic practices. It is usually one of the main active constituents of the drink ayahuasca,[SUP][6][/SUP] however ayahuasca is sometimes brewed with plants which don't produce DMT. It occurs as the primary psychoactive alkaloid in several plants including Mimosa tenuiflora, Diplopterys cabrerana, and Psychotria viridis. DMT is found as a minor alkaloid in snuff made from Virola bark resin in which 5-MeO-DMT is the main active alkaloid.[SUP][86][/SUP] DMT is also found as a minor alkaloid in bark, pods, and beans of Anadenanthera peregrina and Anadenanthera colubrina used to make Yopo and Vilca snuff in which bufotenin is the main active alkaloid.[SUP][86][/SUP][SUP][87][/SUP] Psilocin, an active chemical in many psychedelic mushrooms, is structurally similar to DMT.
The psychotropic effects of DMT were first studied scientifically by the Hungarian chemist and psychologist Dr. Stephen Szára who performed research with volunteers in the mid-1950s. Szára, who later worked for the US National Institutes of Health, had turned his attention to DMT after his order for 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.[SUP][12][/SUP]
DMT during various stages of purification
DMT can produce powerful entheogenic experiences including intense visuals, euphoria and hallucinations (perceived extensions of reality). DMT is generally not active orally unless it is combined with a monoamine oxidase inhibitor (MAOI) such as a reversible inhibitor of monoamine oxidase A (RIMA), for example, harmaline. Without an MAOI, the body quickly metabolizes orally administered DMT, and it therefore has no hallucinogenic effect unless the dose exceeds monoamine oxidase's metabolic capacity. Other means of ingestion such as smoking or injecting the drug can produce powerful hallucinations and entheogenic activity 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 a MAOI prior to smoking or injecting DMT prolongs and potentiates the effects.[SUP][7][/SUP]
[h=3][edit] Inhalation[/h]A standard dose for smoked DMT is between 15–60 mg. This is generally smoked in a few successive breaths. The effects last for a short period of time, usually 5 to 15 minutes, dependent on the dose. The onset after inhalation is very fast (less than 45 seconds) and peak effects are reached within a minute. In the 1960s, some reportedly referred to DMT as "the businessman's trip"[SUP][88][/SUP] because of the relatively short duration of vaporized, insufflated, or injected DMT. The most common way to administer DMT among people who use it is to smoke it. The smoking of DMT is most effectively vaporized through the use of a glass pipe. Combining DMT with plant matter or depositing it upon a substrate of ash also facilitates use of an ordinary smoking pipe or a vaporizer. The vapor is sometimes described as harsh, and some users even compare its flavor to that of burning plastic.
[h=3][edit] Insufflation[/h]Insufflating DMT (commonly as a freebase or fumarate) requires a higher dose than inhalation. The duration is markedly increased, and some users report diminished euphoria but an intensified otherworldly experience.[SUP][citation needed][/SUP]
[h=3][edit] Injection[/h]Injected DMT produces an experience that is similar to inhalation in duration, intensity, and characteristics.
In a study conducted from 1990 through 1995, University of New Mexico psychiatrist Rick Strassman found that some volunteers injected with high doses of DMT had experiences with a perceived alien entity. Usually, the reported entities were experienced as the inhabitants of a perceived independent reality the subjects reported visiting while under the influence of DMT.[SUP][12][/SUP] In a September, 2009, interview with Examiner.com, Strassman described the effects on participants in the study: "Subjectively, the most interesting results were that high doses of DMT seemed to allow the consciousness of our volunteers to enter into non-corporeal, free-standing, independent realms of existence inhabited by beings of light who oftentimes were expecting the volunteers, and with whom the volunteers interacted. While 'typical' near-death and mystical states occurred, they were relatively rare."
[h=3][edit] Oral ingestion[/h]DMT is broken down by the digestive enzyme monoamine oxidase and is practically inactive if taken orally, unless combined with an MAOI. The traditional South American ayahuasca, or yage, is a tea mixture containing DMT and a MAOI.[SUP][6][/SUP] There are a variety of recipes to this brew, but most commonly it is simply the leaves of Psychotria viridis (the source of DMT) and the vine Banisteriopsis caapi (the source of MAOI). Other DMT containing plants, including Diplopterys cabrerana, are sometimes used in ayahuasca in different areas of South America. Two common sources in the western US are Reed canary grass (Phalaris arundinacea) and Harding grass (Phalaris aquatica). These invasive grasses contain low levels of DMT and other alkaloids. In addition, Jurema (Mimosa tenuiflora) shows evidence of DMT content: the pink layer in the bark of this vine contains a high concentration of N,N-DMT.
Taken orally with an appropriate MAOI, DMT produces a long lasting (over 3 hour), slow, deep metaphysical experience similar to that of psilocybin mushrooms, but more intense.[SUP][6][/SUP] MAOIs should be used with extreme caution as they can have lethal complications with some prescription drugs such as SSRI antidepressants, some over-the-counter drugs,[SUP][89][/SUP] and many common foods.[SUP][90][/SUP]
Induced DMT experiences can include profound time-dilation, visual and auditory illusions, and other experiences that, by most firsthand accounts, defy verbal or visual description. Some users report intense erotic imagery and sensations and utilize the drug in a ritual sexual context.[SUP][6][/SUP][SUP][91][/SUP][SUP][92][/SUP]
[h=3][edit] Distinguish from 5-MeO-DMT[/h]5-MeO-DMT, a psychedelic drug structurally similar to N,N-DMT, is sometimes referred to as DMT through abbreviation. As a white, crystalline solid, it is also similar in appearance to DMT. However, it is considerably more potent (5-MeO-DMT typical smoked dose: 5–20 mg), and care should be taken to clearly differentiate between the two drugs to avoid accidental overdose.[SUP][93][/SUP]
[h=2][edit] Detection in body fluids[/h]DMT may be quantitated in blood, plasma or urine using chromatographic techniques as a diagnostic tool in clinical poisoning situations or to aid in the medicolegal investigation of suspicious deaths. Blood or plasma DMT levels in recreational users of the drug are generally in the 10-30 μg/L range during the first several hours post-ingestion.[SUP][citation needed][/SUP] Less than 0.1% of an oral dose is eliminated unchanged in the 24 hour urine of humans.[SUP][94][/SUP][SUP][95][/SUP]
[h=2][edit] Side effects[/h]Similar to other psychedelic drugs, there are relatively few physical side effects associated with DMT acute exposure. Second-hand accounts also exist of serious health complications from 5-MeO-DMT use which may be aggravated by interaction with MAOIs[SUP][96][/SUP][SUP][97][/SUP][SUP][98][/SUP]. When inhaled, its vapor has been described as "very harsh."[SUP][99][/SUP] According to a "Dose-response study of N,N-dimethyltryptamine in humans" by Rick Strassman, "Dimethyltryptamine dose slightly elevated blood pressure, heart rate, pupil diameter, and rectal temperature, in addition to elevating blood concentrations of beta-endorphin, corticotropin, cortisol, and prolactin. Growth hormone blood levels rose equally in response to all doses of DMT, and melatonin levels were unaffected."[SUP][52][/SUP]
Psychologically, the DMT experience can be overly-intense, potentially causing overwhelming fear and difficulty integrating experiences if one is not mentally prepared. Furthermore, due to the intense nature of the experience, DMT is generally considered to have no addiction potential.[SUP][citation needed][/SUP] Just as with all psychedelics, there is a chance for an onset of paranoia, or a 'bad trip'. This risk is more prevalent with DMT, as DMT is more intense than normal psychedelics. Close attention should be paid to dose, set and setting. Also one should note that despite the lack of physical side effects, the intensity of the DMT experience could trigger latent mental illnesses in those who may have a genetic predisposition to such diseases.[SUP][7][/SUP] Because the effects are so short-lived, it has been referred to as the "businessman's trip", implying that the trip lasts no longer than a lunch break
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|---|---|
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| Systematic (IUPAC) name | |
| 2-(1H-indol-3-yl)-N,N-dimethylethanamine | |
| Clinical data | |
| Pregnancy cat. | ? |
| Legal status | Prohibited (S9) (AU) Schedule III (CA) CD Lic (UK) Schedule I (US) |
| Routes | Oral (with an MAOI), Insufflated, Rectal, Smoked (or vaporized), IM, IV |
| Identifiers | |
| CAS number | 61-50-7[SUP]
|
| ATC code | None |
| PubChem | CID 6089 |
| IUPHAR ligand | 141 |
| DrugBank | DB01488 |
| ChemSpider | 5864[SUP]
|
| UNII | WUB601BHAA[SUP]
|
| KEGG | C08302[SUP]
|
| ChEBI | CHEBI:28969[SUP]
|
| ChEMBL | CHEMBL12420[SUP]
|
| Chemical data | |
| Formula | C[SUB]12[/SUB]H[SUB]16[/SUB]N[SUB]2[/SUB] |
| Mol. mass | 188.269 g/mol |
| SMILES | eMolecules & PubChem |
InChI[show]
| |
| Physical data | |
| Density | 1.099g/ml g/cm³ |
| Melt. point | 40 °C (104 °F) |
| Boiling point | 160 °C (320 °F) @ 0.6 Torr[SUP][1][/SUP] also reported as 80 - 135 °C @ 0.03 Torr [SUP][2][/SUP] |
|
MULVCHRPCFFGV-UHFFFAOYSA-N[SUP]
Dimethyltryptamine
In some cultures DMT is ingested as a psychedelic drug (in either extracted or synthesized forms).[SUP][6][/SUP] When DMT is inhaled or consumed, depending on the dose, its subjective effects can range from short-lived milder psychedelic states to powerful immersive experiences, which include a total loss of connection to conventional reality, which may be so extreme that it becomes ineffable.[SUP][7][/SUP] DMT is also the primary psychoactive in ayahuasca, an Amazonian Amerindian brew employed for divinatory and healing purposes. Pharmacologically, ayahuasca combines DMT with an MAOI, an enzyme inhibitor that allows DMT to be orally active.[SUP][8][/SUP]
| [h=2]Contents[/h] [hide] |
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 identify DMT in an "aqueous extract" of leaves of a plant they name Prestonia amazonicum (sic) and describe as "commonly mixed" with B. caapi.[SUP][17][/SUP] The lack of a proper botanical identification of Prestonia amazonica in this study led American ethnobotanist Richard Evans Schultes (1915–2001) and other scientists to raise serious doubts about the claimed plant identity.[SUP][18][/SUP][SUP][19][/SUP] A better evidence is produced in 1965 by French pharmacologist Jacques Poisson who isolates DMT as sole alkaloid from leaves, provided and used by Aguaruna Indians, identified as pertaining to the vine Diplopterys cabrerana (then known as Banisteriopsis rusbyana).[SUP][19][/SUP] Published in 1970, the first identification of DMT in the other commonly used additive plant Psychotria viridis[SUP][11][/SUP] was made by a team of American researchers led by pharmacologist Ara der Marderosian.[SUP][20][/SUP] Not only did they detect DMT in leaves of P. viridis obtained from Cashinahua Indians, but they also were the first to identify it in a sample of an ayahuasca decoction, prepared by the same Indians.[SUP][11][/SUP]
[h=2][edit] Biosynthesis[/h]
Biosynthetic pathway for N,N-dimethyltryptamine
Dimethyltryptamine is an indole alkaloid derived from the shikimate pathway. Its biosynthesis is relatively simple and summarized in the picture to the left. In plants, the parent amino acid L-tryptophan is produced endogenously where in animals L-tryptophan is an essential amino acid coming from diet. No matter the source of L-tryptophan, the biosynthesis begins with its decarboxylation by an aromatic amino acid decarboxylase (AADC) enzyme (step 1). The resulting decarboxylated tryptophan analog is tryptamine. Tryptamine then undergoes a transmethylation (step 2): the enzyme indolethylamine-N-methyltransferase (INMT) catalyzes the transfer of a methyl group from cofactor S-adenosyl-methionine (SAM), via nucleophilic attack, to tryptamine. This reaction transforms SAM into S-adenosylhomocysteine (SAH), and gives the intermediate product N-methyltryptamine (NMT).[SUP][21][/SUP][SUP][22][/SUP] NMT is in turn transmethylated by the same process (step 3) to form the end product N,N-dimethyltryptamine. Tryptamine transmethylation is regulated by two products of the reaction: SAH,[SUP][5][/SUP][SUP][23][/SUP][SUP][24][/SUP] and DMT[SUP][5][/SUP][SUP][24][/SUP] were shown ex vivo to be among the most potent inhibitors of rabbit INMT activity.
This transmethylation mechanism has been repeatedly and consistently proven by radiolabeling of SAM methyl group with carbon-14 ([SUP]14[/SUP]C-CH[SUB]3[/SUB])SAM).[SUP][5][/SUP][SUP][21][/SUP][SUP][24][/SUP][SUP][25][/SUP][SUP][26][/SUP]
[h=3][edit] Evidence in mammals[/h]Published in Science in 1961, Julius Axelrod found an N-methyltransferase enzyme capable of mediating biotransformation of tryptamine into DMT in a rabbit's lung.[SUP][21][/SUP]This finding initiated a still ongoing scientific interest in endogenous DMT production in humans and other mammals.[SUP][22][/SUP][SUP][27][/SUP]From then on, two major complementary lines of evidence have been investigated: localization and further characterization of the N-methyltransferase enzyme, and analytical studies looking for endogenously produced DMT in body fluids and tissues.[SUP][22][/SUP]
[h=4][edit] INMT[/h]Before techniques of molecular biology were used to localize indolethylamine N-methyltransferase (INMT),[SUP][24][/SUP][SUP][26][/SUP] characterization and localization went on a par: samples of the biological material where INMT is hypothesized to be active are subject to enzyme assay. Those enzyme assays are performed either with a radiolabeled methyl donor like ([SUP]14[/SUP]C-CH[SUB]3[/SUB])SAM to which known amounts of unlabeled substrates like tryptamine are added,[SUP][22][/SUP] or with addition of a radiolabeled substrate like ([SUP]14[/SUP]C)NMT to demonstrate in vivo formation.[SUP][5][/SUP][SUP][25][/SUP] As qualitative determination of the radioactively tagged product of the enzymatic reaction is sufficient to characterize INMT existence and activity (or lack of), analytical methods used in INMT assays don't require to be as sensitive as those needed to directly detect and quantify the minute amounts of endogenously formed DMT (see DMT subsection below). The essentially qualitative method thin layer chromatography (TLC) was thus used in a vast majority of studies.[SUP][22][/SUP] Also, robust evidence that INMT can catalyze transmethylation of tryptamine into NMT and DMT could be provided with reverse isotope dilution analysis coupled to mass spectrometry for rabbit[SUP][28][/SUP][SUP][29][/SUP] and human[SUP][30][/SUP] lung during the early 1970s.
Selectivity rather than sensitivity proved to be an Achilles’ heel for some TLC methods with the discovery in 1974-1975 that incubating rat blood cells or brain tissue with ([SUP]14[/SUP]C-CH[SUB]3[/SUB])SAM and NMT as substrate mostly yields tetrahydro-β-carboline derivatives,[SUP][5][/SUP][SUP][22][/SUP][SUP][31][/SUP] and negligible amounts of DMT in brain tissue.[SUP][22][/SUP] 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.[SUP][22][/SUP] These findings are a blow for all previous claims of evidence of INMT activity and DMT biosynthesis in avian[SUP][32][/SUP] and mammalian brain,[SUP][33][/SUP][SUP][34][/SUP] including in vivo,[SUP][35][/SUP][SUP][36][/SUP] as they all relied upon use of the problematic TLC methods[SUP][22][/SUP]: 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.[SUP][37][/SUP][SUP][38][/SUP] 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".[SUP][39][/SUP] Capability of the method used in this latter study to resolve DMT from tetrahydro-β-carbolines is questioned later.[SUP][5][/SUP]
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.[SUP][26][/SUP] Northern blot analyses reveal INMT messenger RNA (mRNA) to be highly expressed in rabbit lung,[SUP][24][/SUP] and in human thyroid, adrenal gland, and lung.[SUP][26][/SUP][SUP][40][/SUP] Intermediate levels of expression are found in human heart, skeletal muscle, trachea, stomach, small intestine, pancreas, testis, prostate, placenta, lymph node, and spinal cord.[SUP][26][/SUP][SUP][40][/SUP] Low to very low levels of expression are noted in rabbit brain,[SUP][26][/SUP] and human thymus, liver, spleen, kidney, colon, ovary, and bone marrow.[SUP][26][/SUP][SUP][40][/SUP] INMT mRNA expression is absent in human peripheral blood leukocytes, whole brain, and in tissue from 7 specific brain regions (thalamus, subthalamic nucleus, caudate nucleus, hippocampus, amygdala, substantia nigra, and corpus callosum).[SUP][26][/SUP][SUP][40][/SUP] Immunohistochemistry showed INMT to be present in large amounts in glandular epithelial cells of small and large intestines, and to be absent in neurons.[SUP][27][/SUP]
[h=4][edit] Endogenous DMT[/h]The first claimed detection of mammalian endogenous DMT 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-OH-DMT), in human blood and urine.[SUP][41][/SUP] In an article published four months later, the method used in their study is strongly criticized, and credibility of their results challenged.[SUP][42][/SUP]
In 2001, surveys, made in research articles, point that few of the analytical methods previously used to measure levels of endogenously formed DMT had enough sensitivity and selectivity to produce reliable results.[SUP][43][/SUP][SUP][44][/SUP] Gas chromatography, preferably coupled to mass spectrometry (GC-MS), is considered a minimum requirement.[SUP][44][/SUP] A study published in 2005[SUP][27][/SUP] implements the most sensitive and selective method ever used to measure endogenous DMT[SUP][45][/SUP]: liquid chromatography-tandem mass spectrometry with electrospray ionization (LC-ESI-MS/MS) allows to reach limits of detection (LODs) 12 to 200 fold lower (that is, better) 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[SUP]−9[/SUP] g) per litre, and nanograms per kilogram, respectively):
| Species | Sample | Results |
|---|---|---|
| Human | Blood serum | < LOD (n = 66)[SUP][27][/SUP] |
| Blood plasma | < LOD (n = 71)[SUP][27][/SUP] ♦ < LOD (n = 3 ; 1,000 & 10,600 ng/L (n = 2)[SUP][46][/SUP] | |
| Whole blood | < LOD (n = 20); 50-790 ng/L (n = 20)[SUP][47][/SUP] | |
| Urine | < 100 ng/L (n = 9)[SUP][27][/SUP] ♦ < LOD (n = 60); 160-540 ng/L (n = 5)[SUP][44][/SUP] ♦ Detected in n = 10 by GC-MS[SUP][48][/SUP] | |
| Feces | < 50 ng/kg (n = 12); 130 ng/kg (n = 1)[SUP][27][/SUP] | |
| Kidney | 15 ng/kg (n = 1)[SUP][27][/SUP] | |
| Lung | 14 ng/kg (n = 1)[SUP][27][/SUP] | |
| Lumbar CSF | 100,370 ng/L (n = 1); 2,330-7,210 ng/L (n = 3); 350 & 850 ng/L (n = 2)[SUP][49][/SUP] | |
| Rat | Kidney | 12 &16 ng/kg (n = 2)[SUP][27][/SUP] |
| Lung | 22 & 12 ng/kg (n = 2)[SUP][27][/SUP] | |
| Liver | 6 & 10 ng/kg (n = 2)[SUP][27][/SUP] | |
| Brain | 10 &15 ng/kg (n = 2)[SUP][27][/SUP] ♦ Measured in synaptic vesicular fraction[SUP][50][/SUP] | |
| Rabbit | Liver | < 10 ng/kg (n = 1)[SUP][27][/SUP] |
DMT Crystals
DMT is commonly handled and stored as a fumarate as other DMT acid salts are generally very hygroscopic and will not readily crystallize. Its freebase form, although less stable than DMT fumarate, is favored by recreational users choosing to vaporize the chemical because it has a lower boiling point. In contrast to DMT's base, its salts are water-soluble. DMT in solution degrades relatively quickly and should be stored protected from air, light, and heat in a freezer.
[h=2][edit] Pharmacology[/h][h=3][edit] Pharmacokinetics[/h]DMT peak levels concentrations (C[SUB]max[/SUB]) measured in whole blood after intramuscular (IM) injection (0.7 mg/kg, n = 11)[SUP][51][/SUP] and in plasma following intravenous (IV) administration (0.4 mg/kg, n = 10)[SUP][52][/SUP] of fully psychedelic doses are in the range of ≈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 µM in whole blood and 0.170–1.08 µM in plasma. However, several studies have described active transport and accumulation of DMT into rat and dog brain following peripheral administration.[SUP][53][/SUP][SUP][54][/SUP][SUP][55][/SUP][SUP][56][/SUP][SUP][57][/SUP] Similar active transport, and accumulation processes likely occur in human brain 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 μM range.[SUP][58][/SUP][SUP][59][/SUP]
Closely coextending with peak psychedelic effects, mean time to reach peak concentrations (T[SUB]max[/SUB]) was determined to be 10–15 minutes in whole blood after IM injection,[SUP][51][/SUP] and 2 minutes in plasma after IV administration.[SUP][52][/SUP] When taken orally mixed in an ayahuasca decoction, and in freeze-dried ayahuasca gel caps, DMT T[SUB]max[/SUB] is considerably delayed: 107.59 ± 32.5 minutes,[SUP][60][/SUP] and 90–120 minutes,[SUP][61][/SUP] respectively. The pharmacokinetics for smoking DMT have not been studied or reported.
[h=3][edit] Pharmacodynamics[/h]DMT binds non-selectively with affinities < 0.6 μM to the following serotonin receptors: 5-HT[SUB]1A[/SUB],[SUP][62][/SUP][SUP][63][/SUP][SUP][64][/SUP] 5-HT[SUB]1B[/SUB],[SUP][62][/SUP][SUP][65][/SUP] 5-HT[SUB]1D[/SUB],[SUP][62][/SUP][SUP][64][/SUP][SUP][65][/SUP] 5-HT[SUB]2A[/SUB],[SUP][62][/SUP][SUP][64][/SUP][SUP][65][/SUP][SUP][66][/SUP] 5-HT[SUB]2B[/SUB],[SUP][62][/SUP][SUP][65][/SUP] 5-HT[SUB]2C[/SUB],[SUP][62][/SUP][SUP][65][/SUP][SUP][66][/SUP] 5-HT6,[SUP][62][/SUP][SUP][65][/SUP] and 5-HT7.[SUP][62][/SUP][SUP][65][/SUP] An agonist action has been determined at 5-HT[SUB]1A[/SUB],[SUP][63][/SUP] 5-HT[SUB]2A[/SUB] and 5-HT[SUB]2C[/SUB].[SUP][62][/SUP][SUP][65][/SUP][SUP][66][/SUP] Its efficacies at other serotonin receptors remain to be determined. Of special interest will be the determination of its efficacy at human 5-HT[SUB]2B[/SUB] receptor as two in vitro assays evidenced DMT high affinity for this receptor: 0.108 μM[SUP][65][/SUP] and 0.184 μM.[SUP][62][/SUP] This may be of importance because chronic or frequent uses of serotonergic drugs showing preferential high affinity and clear agonism at 5-HT[SUB]2B[/SUB] receptor have been causally linked to valvular heart disease.[SUP][67][/SUP][SUP][68][/SUP]
It has also been shown to possess affinity for the dopamine D[SUB]1[/SUB], α[SUB]1[/SUB]-adrenergic, α[SUB]2[/SUB]-adrenergic, imidazoline-1, sigma-1 (σ[SUB]1[/SUB]), and trace amine-associated receptors.[SUP][64][/SUP][SUP][65][/SUP][SUP][69][/SUP] Agonism was demonstrated at 1 μM at the rat trace amine-associated receptor 1 (TAAR1)[SUP][70][/SUP] and converging lines of evidence established activation of the σ[SUB]1[/SUB] receptor at concentrations of 50-100 μM.[SUP][71][/SUP] 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) and the intracellular vesicular monoamine transporter 2 (VMAT2), inhibiting SERT-mediated serotonin uptake in human platelets at an average concentration of 4.00 ± 0.70 μM and VMAT2-mediated serotonin uptake in vesicles (of army worm Sf9 cells) expressing rat VMAT-2 at an average concentration of 93 ± 6.8 μM.[SUP][72][/SUP]
Like with other so-called "classical hallucinogens",[SUP][73][/SUP] a large part of DMT psychedelic effects can be attributed to a specific activation of the 5-HT[SUB]2A[/SUB] receptor.[SUP][52][/SUP][SUP][62][/SUP][SUP][74][/SUP][SUP][75][/SUP][SUP][76][/SUP][SUP][77][/SUP][SUP][78][/SUP] DMT concentrations eliciting 50% of its maximal effect (half maximal effective concentration = EC[SUB]50[/SUB] or K[SUB]act[/SUB]) at the human 5-HT[SUB]2A[/SUB] receptor in vitro are in the 0.118-0.983 μM range.[SUP][62][/SUP][SUP][65][/SUP][SUP][66][/SUP][SUP][79][/SUP] 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).
As DMT has been shown to have slightly better efficacy (EC[SUB]50[/SUB]) at human serotonin 2C receptor than at 2A receptor,[SUP][65][/SUP][SUP][66][/SUP] 5-HT[SUB]2C[/SUB] highly likely also is implicated in DMT overall effects.[SUP][75][/SUP][SUP][80][/SUP] Other receptors, such as 5-HT[SUB]1A[/SUB][SUP][64][/SUP][SUP][75][/SUP][SUP][77][/SUP] σ[SUB]1[/SUB],[SUP][71][/SUP][SUP][81][/SUP] and TAAR1[SUP][70][/SUP][SUP][82][/SUP][SUP][83][/SUP] may also play a role.
In 2009 it was hypothesized that DMT may be an endogenous ligand for the σ[SUB]1[/SUB] receptor.[SUP][71][/SUP][SUP][81][/SUP] The concentration of DMT needed for σ[SUB]1[/SUB] activation in vitro (50-100 μM) is similar to the behaviorally active concentration measured in mouse brain of approximately 106 μM [SUP][84][/SUP] This is minimally 4 orders of magnitude (10[SUP]4[/SUP]) higher than the average concentrations measured in rat brain tissue or human plasma under basal conditions (see Endogenous DMT), so σ[SUB]1[/SUB] receptors are likely to be activated only under conditions of high local DMT concentrations. If DMT is stored in synaptic vesicles,[SUP][72][/SUP] such concentrations might occur during vesicular release. To illustrate, while the average concentration of serotonin in brain tissue is in the 1.5-4 μM range,[SUP][58][/SUP][SUP][59][/SUP] the concentration of serotonin in synaptic vesicles was measured at 270 mM.[SUP][85][/SUP] Following vesicular release, the resulting concentration of serotonin in the synaptic cleft, to which serotonin receptors are exposed, is estimated to be about 300 μM. 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.
[h=2][edit] Psychedelic properties[/h]DMT occurs naturally in many species of plants often in conjunction with its close chemical relatives 5-MeO-DMT and bufotenin (5-OH-DMT).[SUP][86][/SUP] DMT-containing plants are commonly used in South American Shamanic practices. It is usually one of the main active constituents of the drink ayahuasca,[SUP][6][/SUP] however ayahuasca is sometimes brewed with plants which don't produce DMT. It occurs as the primary psychoactive alkaloid in several plants including Mimosa tenuiflora, Diplopterys cabrerana, and Psychotria viridis. DMT is found as a minor alkaloid in snuff made from Virola bark resin in which 5-MeO-DMT is the main active alkaloid.[SUP][86][/SUP] DMT is also found as a minor alkaloid in bark, pods, and beans of Anadenanthera peregrina and Anadenanthera colubrina used to make Yopo and Vilca snuff in which bufotenin is the main active alkaloid.[SUP][86][/SUP][SUP][87][/SUP] Psilocin, an active chemical in many psychedelic mushrooms, is structurally similar to DMT.
The psychotropic effects of DMT were first studied scientifically by the Hungarian chemist and psychologist Dr. Stephen Szára who performed research with volunteers in the mid-1950s. Szára, who later worked for the US National Institutes of Health, had turned his attention to DMT after his order for 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.[SUP][12][/SUP]
DMT during various stages of purification
DMT can produce powerful entheogenic experiences including intense visuals, euphoria and hallucinations (perceived extensions of reality). DMT is generally not active orally unless it is combined with a monoamine oxidase inhibitor (MAOI) such as a reversible inhibitor of monoamine oxidase A (RIMA), for example, harmaline. Without an MAOI, the body quickly metabolizes orally administered DMT, and it therefore has no hallucinogenic effect unless the dose exceeds monoamine oxidase's metabolic capacity. Other means of ingestion such as smoking or injecting the drug can produce powerful hallucinations and entheogenic activity 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 a MAOI prior to smoking or injecting DMT prolongs and potentiates the effects.[SUP][7][/SUP]
[h=3][edit] Inhalation[/h]A standard dose for smoked DMT is between 15–60 mg. This is generally smoked in a few successive breaths. The effects last for a short period of time, usually 5 to 15 minutes, dependent on the dose. The onset after inhalation is very fast (less than 45 seconds) and peak effects are reached within a minute. In the 1960s, some reportedly referred to DMT as "the businessman's trip"[SUP][88][/SUP] because of the relatively short duration of vaporized, insufflated, or injected DMT. The most common way to administer DMT among people who use it is to smoke it. The smoking of DMT is most effectively vaporized through the use of a glass pipe. Combining DMT with plant matter or depositing it upon a substrate of ash also facilitates use of an ordinary smoking pipe or a vaporizer. The vapor is sometimes described as harsh, and some users even compare its flavor to that of burning plastic.
[h=3][edit] Insufflation[/h]Insufflating DMT (commonly as a freebase or fumarate) requires a higher dose than inhalation. The duration is markedly increased, and some users report diminished euphoria but an intensified otherworldly experience.[SUP][citation needed][/SUP]
[h=3][edit] Injection[/h]Injected DMT produces an experience that is similar to inhalation in duration, intensity, and characteristics.
In a study conducted from 1990 through 1995, University of New Mexico psychiatrist Rick Strassman found that some volunteers injected with high doses of DMT had experiences with a perceived alien entity. Usually, the reported entities were experienced as the inhabitants of a perceived independent reality the subjects reported visiting while under the influence of DMT.[SUP][12][/SUP] In a September, 2009, interview with Examiner.com, Strassman described the effects on participants in the study: "Subjectively, the most interesting results were that high doses of DMT seemed to allow the consciousness of our volunteers to enter into non-corporeal, free-standing, independent realms of existence inhabited by beings of light who oftentimes were expecting the volunteers, and with whom the volunteers interacted. While 'typical' near-death and mystical states occurred, they were relatively rare."
[h=3][edit] Oral ingestion[/h]DMT is broken down by the digestive enzyme monoamine oxidase and is practically inactive if taken orally, unless combined with an MAOI. The traditional South American ayahuasca, or yage, is a tea mixture containing DMT and a MAOI.[SUP][6][/SUP] There are a variety of recipes to this brew, but most commonly it is simply the leaves of Psychotria viridis (the source of DMT) and the vine Banisteriopsis caapi (the source of MAOI). Other DMT containing plants, including Diplopterys cabrerana, are sometimes used in ayahuasca in different areas of South America. Two common sources in the western US are Reed canary grass (Phalaris arundinacea) and Harding grass (Phalaris aquatica). These invasive grasses contain low levels of DMT and other alkaloids. In addition, Jurema (Mimosa tenuiflora) shows evidence of DMT content: the pink layer in the bark of this vine contains a high concentration of N,N-DMT.
Taken orally with an appropriate MAOI, DMT produces a long lasting (over 3 hour), slow, deep metaphysical experience similar to that of psilocybin mushrooms, but more intense.[SUP][6][/SUP] MAOIs should be used with extreme caution as they can have lethal complications with some prescription drugs such as SSRI antidepressants, some over-the-counter drugs,[SUP][89][/SUP] and many common foods.[SUP][90][/SUP]
Induced DMT experiences can include profound time-dilation, visual and auditory illusions, and other experiences that, by most firsthand accounts, defy verbal or visual description. Some users report intense erotic imagery and sensations and utilize the drug in a ritual sexual context.[SUP][6][/SUP][SUP][91][/SUP][SUP][92][/SUP]
[h=3][edit] Distinguish from 5-MeO-DMT[/h]5-MeO-DMT, a psychedelic drug structurally similar to N,N-DMT, is sometimes referred to as DMT through abbreviation. As a white, crystalline solid, it is also similar in appearance to DMT. However, it is considerably more potent (5-MeO-DMT typical smoked dose: 5–20 mg), and care should be taken to clearly differentiate between the two drugs to avoid accidental overdose.[SUP][93][/SUP]
[h=2][edit] Detection in body fluids[/h]DMT may be quantitated in blood, plasma or urine using chromatographic techniques as a diagnostic tool in clinical poisoning situations or to aid in the medicolegal investigation of suspicious deaths. Blood or plasma DMT levels in recreational users of the drug are generally in the 10-30 μg/L range during the first several hours post-ingestion.[SUP][citation needed][/SUP] Less than 0.1% of an oral dose is eliminated unchanged in the 24 hour urine of humans.[SUP][94][/SUP][SUP][95][/SUP]
[h=2][edit] Side effects[/h]Similar to other psychedelic drugs, there are relatively few physical side effects associated with DMT acute exposure. Second-hand accounts also exist of serious health complications from 5-MeO-DMT use which may be aggravated by interaction with MAOIs[SUP][96][/SUP][SUP][97][/SUP][SUP][98][/SUP]. When inhaled, its vapor has been described as "very harsh."[SUP][99][/SUP] According to a "Dose-response study of N,N-dimethyltryptamine in humans" by Rick Strassman, "Dimethyltryptamine dose slightly elevated blood pressure, heart rate, pupil diameter, and rectal temperature, in addition to elevating blood concentrations of beta-endorphin, corticotropin, cortisol, and prolactin. Growth hormone blood levels rose equally in response to all doses of DMT, and melatonin levels were unaffected."[SUP][52][/SUP]
Psychologically, the DMT experience can be overly-intense, potentially causing overwhelming fear and difficulty integrating experiences if one is not mentally prepared. Furthermore, due to the intense nature of the experience, DMT is generally considered to have no addiction potential.[SUP][citation needed][/SUP] Just as with all psychedelics, there is a chance for an onset of paranoia, or a 'bad trip'. This risk is more prevalent with DMT, as DMT is more intense than normal psychedelics. Close attention should be paid to dose, set and setting. Also one should note that despite the lack of physical side effects, the intensity of the DMT experience could trigger latent mental illnesses in those who may have a genetic predisposition to such diseases.[SUP][7][/SUP] Because the effects are so short-lived, it has been referred to as the "businessman's trip", implying that the trip lasts no longer than a lunch break
shit be tripping mofo...what you dribblin, I aint dibblin no shit when it comes to mersh, one hit quiiter, my shit says what it has to say and shit.
![[420]Haze](/data/avatars/m/309/309354.jpg?1313548682){kind=avatar}
.coz its easily taken away bro ...by gov or hackers or those with even simplistic hackkn skills ...quite basic man ..let me just ask where da fuck did i say i grow 90% of the weed in my state ....???....and when i did actually join this site ....i was pretty baked and filled shit out drasticly wrong.....id bn trippn 4 days n days of dmt ...n lsd and pretty much fucked up..and obviously filled out shit drasticly wrong due to bn baked of my skull ...simple nuff said ...thinking it was possible to change my user name later ..tho bn tryna change my handle ......which i thought would be possible.....as it is on almost every site ......but seems to harder to do here ...but .ive actually bn buisy ..excuse me ..
