Dimethyltryptamine

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Dimethyltryptamine
DMT.svg
Dimethyltryptamine 27feb.gif
Systematic (IUPAC) name
2-(1H-indol-3-yl)-N,N-dimethylethanamine
Clinical data
Legal status Prohibited (S9) (AU) Schedule III (CA) CD Lic (UK) Schedule I (US)
Routes Oral (with an MAOI), Insufflated, Rectal, vaporized, IM, IV
Identifiers
CAS number 61-50-7 N
ATC code None
PubChem CID 6089
IUPHAR ligand 141
DrugBank DB01488
ChemSpider 5864 YesY
UNII WUB601BHAA YesY
KEGG C08302 YesY
ChEBI CHEBI:28969 YesY
ChEMBL CHEMBL12420 YesY
Chemical data
Formula C12H16N2 
Mol. mass 188.269 g/mol
Physical data
Density 1.099 g/cm³
Melt. point 40 °C (104 °F)
Boiling point 160 °C (320 °F)
@ 0.6 Torr (80 Pa)[1]
also reported as
80–135 °C (176–275 °F)
@ 0.03 Torr (4.0 Pa)[2]
 N (what is this?)  (verify)

N,N-Dimethyltryptamine (DMT or N,N-DMT) is a psychedelic compound of the tryptamine family. Since DMT resembles the basic structure of neurotransmitters, when ingested, DMT is able to cross the human blood-brain-barrier, allowing it to act as a powerful hallucinogenic drug that dramatically affects human consciousness.[3] Depending on the dose and method of administration, its subjective effects can range from short-lived, milder psychedelic states to powerful immersive experiences; these are often described as a total loss of connection to external reality and an experience of encountering indescribable spiritual/alien beings and realms.[4] Indigenous Amazonian Amerindian cultures consume DMT as the primary psychoactive chemical (one that affects the mind) in ayahuasca, a shamanistic brew used for divinatory and healing purposes. In terms of pharmacology, ayahuasca combines DMT with an MAOI, an enzyme inhibitor that allows DMT to be orally active.[5] Its presence is widespread throughout the plant kingdom.[6][7] DMT occurs in trace amounts in mammals, where it functions as a neurotransmitter and putatively as a neuromodulator. DMT is also produced in humans; however, its production and purpose in the brain has yet to be proven or understood. [8] It is originally derived from the essential amino acid tryptophan and ultimately produced by the enzyme INMT during normal metabolism.[9] The significance of its widespread natural presence remains undetermined. DMT is structurally analogous to the neurotransmitter serotonin (5-HT) and the hormone melatonin, and furthermore functionally analogous to other psychedelic tryptamines, such as 5-MeO-DMT, bufotenin, psilocin, and psilocybin.

History[edit]

DMT was first synthesized in 1931 by Canadian chemist Richard Helmuth Fredrick Manske (1901–1977).[10][11] In general, its discovery as a natural product is 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.[11][12][13] 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.[14] 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.[14][15] 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).[14][16] Since 1955 DMT has been found in a host of organisms: in at least fifty plant species belonging to ten families,[6] and in at least four animal species, including one gorgonian[17] and three mammalian species.

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.[18] 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.[19][20] 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 Indians, identified as having come from the vine Diplopterys cabrerana (then known as Banisteriopsis rusbyana).[20] Published in 1970, the first identification of DMT in the plant Psychotria viridis,[12] another common additive of ayahuasca, was made by a team of American researchers led by pharmacologist Ara der Marderosian.[21] 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.[12]

Biosynthesis[edit]

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).[22][23] 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,[9][24][25] and DMT[9][25] 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 (14C-CH3)SAM).[9][22][25][26][27]

Evidence in mammals[edit]

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.[22] This finding initiated a still ongoing scientific interest in endogenous DMT production in humans and other mammals.[23][28] 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.[23]

In 2013, researchers first reported DMT in the pineal gland microdialysate of rodents.[29]

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. [30]

INMT[edit]

Before techniques of molecular biology were used to localize indolethylamine N-methyltransferase (INMT),[25][27] 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 (14C-CH3)SAM to which known amounts of unlabeled substrates like tryptamine are added[23] or with addition of a radiolabeled substrate like (14C)NMT to demonstrate in vivo formation.[9][26] 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 are not required 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.[23] 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[31][32] and human[33] 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 (14C-CH3)SAM and NMT as substrate mostly yields tetrahydro-β-carboline derivatives,[9][23][34] and negligible amounts of DMT in brain tissue.[23] 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.[23] These findings are a blow for all previous claims of evidence of INMT activity and DMT biosynthesis in avian[35] and mammalian brain,[36][37] including in vivo,[38][39] as they all relied upon use of the problematic TLC methods:[23] 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.[40][41] 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".[42] Capability of the method used in this latter study to resolve DMT from tetrahydro-β-carbolines is questioned later.[9]
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.[27] Northern blot analyses reveal INMT messenger RNA (mRNA) to be highly expressed in rabbit lung,[25] and in human thyroid, adrenal gland, and lung.[27][43] Intermediate levels of expression are found in human heart, skeletal muscle, trachea, stomach, small intestine, pancreas, testis, prostate, placenta, lymph node, and spinal cord.[27][43] Low to very low levels of expression are noted in rabbit brain,[27] and human thymus, liver, spleen, kidney, colon, ovary, and bone marrow.[27][43] 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).[27][43] Immunohistochemistry showed INMT to be present in large amounts in glandular epithelial cells 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.[44]

Endogenous DMT[edit]

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.[45] In an article published four months later, the method used in their study is strongly criticized, and credibility of their results challenged.[46]

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.[47][48] Gas chromatography, preferably coupled to mass spectrometry (GC-MS), is considered a minimum requirement.[48] A study published in 2005[28] implements the most sensitive and selective method ever used to measure endogenous DMT:[49] liquid chromatography-tandem mass spectrometry with electrospray ionization (LC-ESI-MS/MS) allows for reaching 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 (10−9 g) per litre, and nanograms per kilogram, respectively):

DMT in body fluids and tissues (NB: units have been harmonized)
Species Sample Results
Human Blood serum < LOD (n = 66)[28]
Blood plasma < LOD (n = 71)[28]  ♦  < LOD (n = 38); 1,000 & 10,600 ng/L (n = 2)[50]
Whole blood < LOD (n = 20); 50–790 ng/L (n = 20)[51]
Urine < 100 ng/L (n = 9)[28]  ♦  < LOD (n = 60); 160–540 ng/L (n = 5)[48]  ♦  Detected in n = 10 by GC-MS[52]
Feces < 50 ng/kg (n = 12); 130 ng/kg (n = 1)[28]
Kidney 15 ng/kg (n = 1)[28]
Lung 14 ng/kg (n = 1)[28]
Lumbar CSF 100,370 ng/L (n = 1); 2,330–7,210 ng/L (n = 3); 350 & 850 ng/L (n = 2)[53]
Rat Kidney 12 &16 ng/kg (n = 2)[28]
Lung 22 & 12 ng/kg (n = 2)[28]
Liver 6 & 10 ng/kg (n = 2)[28]
Brain 10 &15 ng/kg (n = 2)[28]  ♦  Measured in synaptic vesicular fraction[54]
Rabbit Liver < 10 ng/kg (n = 1)[28]

A 2013 study found DMT in microdialysate obtained from a rat's pineal gland, providing evidence of endogenous DMT in the mammalian brain.[29]

Physical and chemical properties[edit]

DMT crystals
DMT crystal at 400x magnification

DMT is commonly handled and stored as a fumarate,[citation needed] in general as other DMT acid salts are 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.[citation needed] 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.[citation needed]

As Distinguished from 5-MeO-DMT[edit]

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 vaporized dose: 5–20 mg), and care should be taken to clearly differentiate between the two drugs to avoid accidental overdose.[55]

Pharmacology[edit]

Pharmacokinetics[edit]

DMT peak level concentrations (Cmax) measured in whole blood after intramuscular (IM) injection (0.7 mg/kg, n = 11)[56] and in plasma following intravenous (IV) administration (0.4 mg/kg, n = 10)[57] 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.[58][59][60][61][62] 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.[63][64]

Closely coextending with peak psychedelic effects, mean time to reach peak concentrations (Tmax) was determined to be 10–15 minutes in whole blood after IM injection,[56] and 2 minutes in plasma after IV administration.[57] When taken orally mixed in an ayahuasca decoction, and in freeze-dried ayahuasca gel caps, DMT Tmax is considerably delayed: 107.59 ± 32.5 minutes,[65] and 90–120 minutes,[66] respectively. The pharmacokinetics for vaporizing DMT have not been studied or reported.

Pharmacodynamics[edit]

DMT binds non-selectively with affinities < 0.6 μM to the following serotonin receptors: 5-HT1A,[67][68][69] 5-HT1B,[67][70] 5-HT1D,[67][69][70] 5-HT2A,[67][69][70][71] 5-HT2B,[67][70] 5-HT2C,[67][70][71] 5-HT6,[67][70] and 5-HT7.[67][70] An agonist action has been determined at 5-HT1A,[68] 5-HT2A and 5-HT2C.[67][70][71] 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 μM[70] and 0.184 μM.[67] 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.[72][73][74]

It has also been shown to possess affinity for the dopamine D1, α1-adrenergic, α2-adrenergic, imidazoline-1, and sigma-11) receptors.[8][69][70] Converging lines of evidence established activation of the σ1 receptor at concentrations of 50–100 μM.[75] 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 VMAT2 at an average concentration of 93 ± 6.8 μM.[76]

As with other so-called "classical hallucinogens",[77] a large part of DMT psychedelic effects can be attributed to a functionally selective activation of the 5-HT2A receptor.[57][67][78][79][80][81][82] DMT concentrations eliciting 50% of its maximal effect (half maximal effective concentration = EC50 or Kact) at the human 5-HT2A receptor in vitro are in the 0.118–0.983 μM range.[67][70][71][83] 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 (EC50) at human serotonin 2C receptor than at the 2A receptor,[70][71] 5-HT2C is also likely implicated in DMT's overall effects.[79][84] Other receptors, such as 5-HT1A[69][79][81] σ1,[75][85] may also play a role.

In 2009, it was hypothesized that DMT may be an endogenous ligand for the σ1 receptor.[75][85] The concentration of DMT needed for σ1 activation in vitro (50–100 μM) is similar to the behaviorally active concentration measured in mouse brain of approximately 106 μM [86] 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,[76] 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,[63][64] the concentration of serotonin in synaptic vesicles was measured at 270 mM.[87] 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.

As a psychedelic[edit]

DMT during various stages of purification

DMT is produced naturally in many species of plants often in conjunction with its close chemical relatives 5-MeO-DMT and bufotenin (5-OH-DMT).[88] DMT-containing plants are commonly used in South American Shamanic practices. It is usually one of the main active constituents of the drink ayahuasca;[89][90] however, ayahuasca is sometimes brewed with plants that do not 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.[88] 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.[88][91] 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.[13]

DMT can produce powerful psychedelic experiences including intense visuals, euphoria and hallucinations.[4] 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.[5] 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 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 a MAOI prior to vaporizing or injecting DMT prolongs and potentiates the effects.[4]

Pseudohallucinations about intelligent beings[edit]

References to pseudohallucinations about intelligent beings can be found in many cultures ranging from shamanic traditions of native Americans to indigenous Australians and African tribes, as well as among western users of this substance.[92] Terence McKenna used the term "machine elves" to describe pseudohallucinations he experienced while taking dimethyltryptamine.[93][94] Peter Meyer also spoke about the DMT elves; he reported a subject's experience of the elves after ingestion of DMT: "The elves were dancing in and out of the multidimensional visible language matrix".[95] Meyer associates this experience with that talked about by Walter Evans-Wentz, who expressed that a world of entities such as fairies and elves exists "as a supernormal state of consciousness into which men and women may enter temporarily in dreams, trances, or in various ecstatic conditions".[96] Psychiatrist Rick Strassman reported that many DMT smokers had experienced similar pseudohallucinations.[94]

Routes of administration[edit]

Inhalation[edit]

A standard dose for vaporized DMT is between 15–60 mg. In general, this is inhaled 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, DMT was known as a "businessman's lunch" in the US because of the relatively short duration (and rapid onset) of action when inhaled.[97]

Injection[edit]

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 reported experiences with perceived alien entities. Usually, the reported entities were experienced as the inhabitants of a perceived independent reality the subjects reported visiting while under the influence of DMT.[13] 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."

Oral ingestion[edit]

DMT is broken down by the enzyme monoamine oxidase through a process called deamination, and is therefore inactive if taken orally unless combined with a monoamine oxidase inhibitor (MAOI).[5] The traditional South American beverage ayahuasca, or yage, is derived by boiling the ayahuasca vine (Banisteriopsis caapi) with leaves of one or more plants containing DMT, such as Psychotria viridis, Psychotria carthagenensis, or Diplopterys cabrerana.[5] The Ayahuasca vine contains harmala alkaloids,[98] highly active reversible inihibitors of monoamine oxidase A (RIMAs),[99] rendering the DMT orally active by protecting it from deamination.[5] A variety of different recipes are used to make the brew depending on the purpose of the ayahuasca session,[100] or local availability of ingredients. Two common sources of DMT 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 inner rootbark of this small tree contains a high concentration of N,N-DMT.[citation needed]

Taken orally with an RIMA, DMT produces a long lasting (over 3 hour), slow, deep metaphysical experience similar to that of psilocybin mushrooms, but more intense.[3] RIMAs should be used with caution as they can have lethal complications with some prescription drugs such as SSRI antidepressants, and some over-the-counter drugs.[98]

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.[3][101][102]

Detection in body fluids[edit]

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. In general, blood or plasma DMT levels in recreational users of the drug are in the 10–30 μg/L range during the first several hours post-ingestion.[citation needed] Less than 0.1% of an oral dose is eliminated unchanged in the 24-hour urine of humans.[103][104][clarification needed]

Effects[edit]

Addictive potential[edit]

A review of studies on ritual users of the DMT-containing brew Ayahuasca concluded that: "A decoction of DMT and harmala alkaloids used in religious ceremonies has a safety margin comparable to codeine, mescaline or methadone. The dependence potential of oral DMT and the risk of sustained psychological disturbance are minimal." [105]

Physical[edit]

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."[57]

Conjecture[edit]

Several speculative and yet untested hypotheses suggest that endogenous DMT is produced in the human brain and is involved in certain psychological and neurological states.[106][107] DMT is naturally occurring in small amounts in rat brain, human cerebrospinal fluid, and other tissues of humans and other mammals.[28][53][54][108] A biochemical mechanism for this was proposed by the medical researcher J. C. Callaway, who suggested in 1988 that DMT might be connected with visual dream phenomena: brain DMT levels would be periodically elevated to induce visual dreaming and possibly other natural states of mind.[109] A role of endogenous hallucinogens including DMT in higher level sensory processing and awareness was proposed by J. V. Wallach based on the proposed role of DMT as a neurotransmitter.[110]

Dr. Rick Strassman, while conducting DMT research in the 1990s at the University of New Mexico, advanced the controversial hypothesis that a massive release of DMT from the pineal gland prior to death or near death was the cause of the near death experience (NDE) phenomenon. Several of his test subjects reported audio or visual hallucinations. His explanation for this was the possible lack of panic involved in the clinical setting and possible dosage differences between those administered and those encountered in actual NDE cases. Several subjects also reported contact with "other beings", alien like, insectoid or reptilian in nature, in highly advanced technological environments[13] where the subjects were "carried", "probed", "tested", "manipulated", "dismembered", "taught", "loved" and "raped" by these "beings". Basing his reasoning on his belief that all the enzymatic material needed to produce DMT is found in the pineal gland, and moreover in substantially greater concentrations than in any other part of the body, Strassman has speculated that DMT is made in the pineal gland([13] p. 69) .

In the 1950s, the endogenous production of psychoactive agents was considered to be a potential explanation for the hallucinatory symptoms of some psychiatric diseases; this is known as the transmethylation hypothesis.[111]

In 2011, Nicholas V. Cozzi, of the University of Wisconsin School of Medicine and Public Health, concluded that INMT, an enzyme that may be associated with the biosynthesis of DMT and endogenous hallucinogens, is present in the primate (rhesus macaque) pineal gland, retinal ganglion neurons, and spinal cord.[44]

Legal status[edit]

International law[edit]

DMT is classified as a Schedule I drug under the UN 1971 Convention on Psychotropic Substances, meaning that use of DMT is supposed to be restricted to scientific research and medical use and international trade in DMT is supposed to be closely monitored. Natural materials containing DMT, including ayahuasca, are explicitly not regulated under the 1971 Psychotropic Convention.[112]

By country[edit]

Australia[edit]

Between 2011 and 2012, the Australian Federal Government was considering changes to the Australian Criminal Code that would classify any plants containing any amount of DMT as "controlled plants".[113] DMT itself was already controlled under current laws. The proposed changes included other similar blanket bans for other substances, such as a ban on any and all plants containing Mescaline or Ephedrine. The proposal was not pursued after political embarrassment on realisation that this would make the official Floral Emblem of Australia, Acacia pycnantha (Golden Wattle), illegal. The Therapeutic Goods Administration and federal authority had considered a motion to ban the same, but this was withdrawn in May 2012 (as DMT may still hold potential entheogenic value to native and/or religious peoples).[114]

Canada[edit]

DMT is classified in Canada as a Schedule III drug under the Controlled Drugs and Substances Act, a federal regulation.

France[edit]

DMT, along with most of its plant sources, is classified in France as a stupéfiant (narcotic).

New Zealand[edit]

DMT is classified in New Zealand as a Class A drug under the Misuse of Drugs Act 1975.[115][116]

United Kingdom[edit]

DMT is classified in the United Kingdom as a Class A drug.

United States[edit]

DMT is classified in the United States as a Schedule I drug under the Controlled Substances Act of 1970.

In December 2004, the Supreme Court lifted a stay, thereby allowing the Brazil-based União do Vegetal (UDV) 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 Espirita Beneficente Uniao 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.

In September 2008, the three Santo Daime churches filed suit in federal court to gain legal status to import DMT-containing ayahuasca tea. The case, Church of the Holy Light of the Queen v. Mukasey,[117] presided over by Judge Owen M. Panner, was ruled in favor of the Santo Daime church. As of March 21, 2009, a federal judge says members of the church in Ashland can import, distribute and brew ayahuasca. U.S. District Judge Owen Panner issued a permanent injunction barring the government from prohibiting or penalizing the sacramental use of "Daime tea". Panner's order said activities of The Church of the Holy Light of the Queen are legal and protected under freedom of religion. His order prohibits the federal government from interfering with and prosecuting church members who follow a list of regulations set out in his order.[118]

See also[edit]

References[edit]

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