Jump to content

N,N-Dimethyltryptamine

From Wikipedia, the free encyclopedia

This is an old revision of this page, as edited by RotogenRay (talk | contribs) at 02:51, 11 August 2014 (→‎Oral ingestion: Alkalemia). The present address (URL) is a permanent link to this revision, which may differ significantly from the current revision.

N,N-Dimethyltryptamine
Clinical data
Routes of
administration		Oral (with an MAOI), Insufflated, Rectal, vaporized, IM, IV
ATC code
  • none
Legal status
Legal status
Identifiers
  • 2-(1H-indol-3-yl)-N,N-dimethylethanamine
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.000.463 Edit this at Wikidata
Chemical and physical data
FormulaC12H16N2
Molar mass188.269 g/mol g·mol−1
3D model (JSmol)
Density1.099 g/cm3
Melting point40 °C (104 °F)
Boiling point160 °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]
  • CN(CCC1=CNC2=C1C=CC=C2)C
  • InChI=1S/C12H16N2/c1-14(2)8-7-10-9-13-12-6-4-3-5-11(10)12/h3-6,9,13H,7-8H2,1-2H3 checkY
  • Key:DMULVCHRPCFFGV-UHFFFAOYSA-N checkY
 ☒NcheckY (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 a 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

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

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

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

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

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

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

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

Pharmacokinetics

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

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-1 (σ1) 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

File:Dmtlab.jpg
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

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

Inhalation

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 trip" in the US because of the relatively short duration (and rapid onset) of action when inhaled.[97]

Injection

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

DMT is broken down by the enzyme monoamine oxidase through a process called deamination, and is quickly inactivated 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] Lethal complications may still occur with orally potentiated DMT, especially in the form of ayahuasca as the dose of the active constituents is at best an estimate. Excessive undigested DMT may cause fatal respiratory depression from alkalemia which may be counteracted by vinegar or lemon juice.

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

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

Addictive potential

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

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

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

International law

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

Australia

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

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

France

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

New Zealand

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

United Kingdom

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

United States

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

Template:Multicol

Template:Multicol-break

Template:Multicol-break

People

Template:Multicol-end

References

  1. ^ Häfelinger, G.; Nimtz, M.; Horstmann, V.; Benz, T. (1999). "Untersuchungen zur Trifluoracetylierung der Methylderivate von Tryptamin und Serotonin mit verschiedenen Derivatisierungsreagentien: Synthesen, Spektroskopie sowie analytische Trennungen mittels Kapillar-GC". Zeitschrift für Naturforschung B. 54 (3): 397–414. {{cite journal}}: Unknown parameter |trans_title= ignored (|trans-title= suggested) (help)
  2. ^ Corothie, E; Nakano, T (1969). "Constituents of the bark of Virola sebifera". Planta Medica. 17 (2): 184–188. doi:10.1055/s-0028-1099844. PMID 5792479.
  3. ^ a b c Salak, Kira. "Hell and back". National Geographic Adventure.
  4. ^ a b c "Erowid DMT (Dimethyltryptamine) Vault". Erowid.org. Retrieved 2012-09-20.
  5. ^ a b c d e McKenna, Dennis J.; Towers, G.H.N.; Abbott, F. (April 1984). "Monoamine oxidase inhibitors in South American hallucinogenic plants: tryptamine and β-carboline constituents of ayahuasca". Journal of Ethnopharmacology. 10 (2): 195–223. doi:10.1016/0378-8741(84)90003-5. ISSN 0378-8741. PMID 6587171.
  6. ^ a b Ott, Jonathan (1994). Ayahuasca Analogues: Pangæan Entheogens (1st ed.). Kennewick, WA, USA: Natural Products. pp. 81–3. ISBN 978-0-9614234-5-2. OCLC 32895480.
  7. ^ Shulgin, Alexander; Shulgin, Ann (1997). "DMT is Everywhere". TiHKAL: The Continuation (1st ed.). Berkeley, CA, USA: Transform Press. pp. 247–84. ISBN 978-0-9630096-9-2. OCLC 38503252. Retrieved 9 May 2012. {{cite book}}: External link in |chapterurl= (help); Unknown parameter |chapterurl= ignored (|chapter-url= suggested) (help)
  8. ^ a b Burchett, Scott A.; Hicks, T. Philip (August 2006). "The mysterious trace amines: Protean neuromodulators of synaptic transmission in mammalian brain" (PDF). Progress in Neurobiology. 79 (5–6): 223–46. doi:10.1016/j.pneurobio.2006.07.003. ISSN 0301-0082. OCLC 231983957. PMID 16962229. Retrieved 9 May 2012.
  9. ^ a b c d e f g Barker S.A., Monti J.A., Christian S.T. (1981). "N, N-dimethyltryptamine: an endogenous hallucinogen". International Review of Neurobiology. International Review of Neurobiology. 22: 83–110. doi:10.1016/S0074-7742(08)60291-3. ISBN 978-0-12-366822-6. PMID 6792104.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  10. ^ Manske R.H.F. (1931). "A synthesis of the methyltryptamines and some derivatives". Canadian Journal of Research. 5 (5): 592–600. doi:10.1139/cjr31-097.
  11. ^ a b Bigwood J., Ott J. (November 1977). "DMT: the fifteen minute trip". Head. 2 (4): 56–61. Archived from the original on 2006-01-27. Retrieved 2010-11-28.
  12. ^ a b c Ott, Jonathan (1996). Pharmacotheon: Entheogenic Drugs, Their Plant Sources and History (2nd, densified ed.). Kennewick, WA: Natural Products. ISBN 978-0-9614234-9-0.
  13. ^ a b c d e Strassman, Rick J. (2001). DMT: The Spirit Molecule. A Doctor's Revolutionary Research into the Biology of Near-Death and Mystical Experiences. Rochester, Vt: Park Street. ISBN 978-0-89281-927-0. ("Chapter summaries". Retrieved 27 February 2012.) Cite error: The named reference "strassman" was defined multiple times with different content (see the help page).
  14. ^ a b c Ott, Jonathan (1998). "Pharmahuasca, anahuasca and vinho da jurema: human pharmacology of oral DMT plus harmine". In Müller-Ebeling, C. (ed.). Special: Psychoactivity. Yearbook for Ethnomedicine and the Study of Consciousness. Vol. 6/7 (1997/1998). Berlin: VWB. ISBN 3-86135-033-5. {{cite book}}: External link in |chapterurl= (help); Unknown parameter |chapterurl= ignored (|chapter-url= suggested) (help)
  15. ^ Pachter I.J., Zacharias D.E., Ribeiro O. (September 1959). "Indole alkaloids of Acer saccharinum (the silver maple), Dictyoloma incanescens, Piptadenia colubrina, and Mimosa hostilis". Journal of Organic Chemistry. 24 (9): 1285–87. doi:10.1021/jo01091a032.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  16. ^ Fish M.S., Johnson N.M., Horning E.C. (November 1955). "Piptadenia alkaloids. Indole bases of P. peregrina (L.) Benth. and related species". Journal of the American Chemical Society. 72 (22): 5892–95. doi:10.1021/ja01627a034.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  17. ^ Cimino G., De Stefano S. (1978). "Chemistry of Mediterranean gorgonians: simple indole derivatives from Paramuricea chamaeleon". Comparative Biochemistry and Physiology Part C: Comparative Pharmacology. 61 (2): 361–2. doi:10.1016/0306-4492(78)90070-9.
  18. ^ Hochstein F.A., Paradies A.M. (1957). "Alkaloids of Banisteria caapi and Prestonia amazonicum". Journal of the American Chemical Society. 79 (21): 5735–36. doi:10.1021/ja01578a041.
  19. ^ Schultes R.E., Raffauf R.F. (1960). "Prestonia: An Amazon narcotic or not?". Botanical Museum Leaflets, Harvard University. 19 (5): 109–122. ISSN 0006-8098.
  20. ^ a b Poisson J. (April 1965). "Note sur le "Natem", boisson toxique péruvienne et ses alcaloïdes". Annales Pharmaceutiques Françaises (in French). 23: 241–4. ISSN 0003-4509. PMID 14337385. {{cite journal}}: Unknown parameter |trans_title= ignored (|trans-title= suggested) (help)
  21. ^ Der Marderosian A.H., Kensinger K.M., Chao J.-M., Goldstein F.J. (1970). "The use and hallucinatory principles of a psychoactive beverage of the Cashinahua tribe (Amazon basin)". Drug Dependence. 5: 7–14. ISSN 0070-7368. OCLC 1566975.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  22. ^ a b c Axelrod J. (August 1961). "Enzymatic formation of psychotomimetic metabolites from normally occurring compounds". Science. 134 (3475): 343. doi:10.1126/science.134.3475.343. PMID 13685339.
  23. ^ a b c d e f g h i Rosengarten H., Friedhoff A.J. (1976). "A review of recent studies of the biosynthesis and excretion of hallucinogens formed by methylation of neurotransmitters or related substances" (PDF). Schizophrenia Bulletin. 2 (1): 90–105. doi:10.1093/schbul/2.1.90. PMID 779022.
  24. ^ Lin R.L., Narasimhachari N., Himwich H.E. (September 1973). "Inhibition of indolethylamine-N-methyltransferase by S-adenosylhomocysteine". Biochemical and Biophysical Research Communications. 54 (2): 751–9. doi:10.1016/0006-291X(73)91487-3. PMID 4756800.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  25. ^ a b c d e Thompson M.A., Weinshilboum R.M. (December 1998). "Rabbit lung indolethylamine N-methyltransferase. cDNA and gene cloning and characterization". Journal of Biological Chemistry. 273 (51): 34502–10. doi:10.1074/jbc.273.51.34502. PMID 9852119. Retrieved 2010-11-09.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  26. ^ a b Mandel L.R., Prasad R., Lopez-Ramos B., Walker R.W. (January 1977). "The biosynthesis of dimethyltryptamine in vivo". Research Communications in Chemical Pathology and Pharmacology. 16 (1): 47–58. PMID 14361.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  27. ^ a b c d e f g h Thompson M.A., Moon E., Kim U.J., Xu J., Siciliano M.J., Weinshilboum R.M. (November 1999). "Human indolethylamine N-methyltransferase: cDNA cloning and expression, gene cloning, and chromosomal localization" (PDF). Genomics. 61 (3): 285–97. doi:10.1006/geno.1999.5960. PMID 10552930.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  28. ^ a b c d e f g h i j k l m n Kärkkäinen J., Forsström T., Tornaeus J., Wähälä K., Kiuru P., Honkanen A., Stenman U.-H., Turpeinen U., Hesso A. (April 2005). "Potentially hallucinogenic 5-hydroxytryptamine receptor ligands bufotenine and dimethyltryptamine in blood and tissues". Scandinavian Journal of Clinical and Laboratory Investigation. 65 (3): 189–199. doi:10.1080/00365510510013604. PMID 16095048.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  29. ^ a b Barker SA, Borjigin J, Lomnicka I, Strassman R (Jul 2013). "LC/MS/MS analysis of the endogenous dimethyltryptamine hallucinogens, their precursors, and major metabolites in rat pineal gland microdialysate". Biomed Chromatogr. doi:10.1002/bmc.2981. PMID 23881860.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  30. ^ Gomes MM, Coimbra JB, Clara RO, Dörr FA, Moreno AC, Chagas JR, Tufik S, Pinto E Jr, Catalani LH, Campa A. (2014). "Biosynthesis of N,N-dimethyltryptamine (DMT) in a melanoma cell line and its metabolization by peroxidases". Biochemica Pharmacology. 88 (3): 393–401. doi:10.1016/j.bcp.2014.01.035. PMID 24508833.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  31. ^ Mandel L.R., Rosenzweig S., Kuehl F.A. (March 1971). "Purification and substrate specificity of indoleamine-N-methyl transferase". Biochemical Pharmacology. 20 (3): 712–6. doi:10.1016/0006-2952(71)90158-4. PMID 5150167.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  32. ^ Lin R.-L., Narasimhachari N. (June 1975). "N-methylation of 1-methyltryptamines by indolethylamine N-methyltransferase". Biochemical Pharmacology. 24 (11–12): 1239–40. doi:10.1016/0006-2952(75)90071-4. PMID 1056183.
  33. ^ Mandel L.R., Ahn H.S., VandenHeuvel W.J. (April 1972). "Indoleamine-N-methyl transferase in human lung". Biochemical Pharmacology. 21 (8): 1197–200. doi:10.1016/0006-2952(72)90113-X. PMID 5034200.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  34. ^ Rosengarten H., Meller E., Friedhoff A.J. (1976). "Possible source of error in studies of enzymatic formation of dimethyltryptamine". Journal of Psychiatric Research. 13 (1): 23–30. doi:10.1016/0022-3956(76)90006-6. PMID 1067427.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  35. ^ Morgan M., Mandell A.J. (August 1969). "Indole(ethyl)amine N-methyltransferase in the brain". Science. 165 (3892): 492–3. doi:10.1126/science.165.3892.492. PMID 5793241.
  36. ^ Mandell A.J., Morgan M. (March 1971). "Indole(ethyl)amine N-methyltransferase in human brain". Nature: New Biology. 230 (11): 85–7. doi:10.1038/newbio230085a0. PMID 5279043.
  37. ^ Saavedra J.M., Coyle J.T., Axelrod J. (March 1973). "The distribution and properties of the nonspecific N-methyltransferase in brain". Journal of Neurochemistry. 20 (3): 743–52. doi:10.1111/j.1471-4159.1973.tb00035.x. PMID 4703789.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  38. ^ Saavedra J.M., Axelrod J. (March 1972). "Psychotomimetic N-methylated tryptamines: formation in brain in vivo and in vitro" (PDF). Science. 175 (4028): 1365–6. doi:10.1126/science.175.4028.1365. PMID 5059565.
  39. ^ Wu P.H., Boulton A.A. (July 1973). "Distribution and metabolism of tryptamine in rat brain". Canadian Journal of Biochemistry. 51 (7): 1104–12. doi:10.1139/o73-144. PMID 4725358.
  40. ^ Boarder M.R., Rodnight R. (September 1976). "Tryptamine-N-methyltransferase activity in brain tissue: a re-examination". Brain Research. 114 (2): 359–64. doi:10.1016/0006-8993(76)90680-6. PMID 963555.
  41. ^ Gomes U.R., Neethling A.C., Shanley B.C. (September 1976). "Enzymatic N-methylation of indoleamines by mammalian brain: fact or artefact?". Journal of Neurochemistry. 27 (3): 701–5. doi:10.1111/j.1471-4159.1976.tb10397.x. PMID 823298.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  42. ^ Stramentinoli G., Baldessarini R.J. (October 1978). "Lack of enhancement of dimethyltryptamine formation in rat brain and rabbit lung in vivo by methionine or S-adenosylmethionine". Journal of Neurochemistry. 31 (4): 1015–20. doi:10.1111/j.1471-4159.1978.tb00141.x. PMID 279646.
  43. ^ a b c d General annotation of Human INMT (O95050) entry in UniProtKB/Swiss-Prot
  44. ^ a b Cozzi N.V., Mavlyutov T.A., Thompson M.A., Ruoho A.E. (2011). "Indolethylamine N-methyltransferase expression in primate nervous tissue" (PDF). Society for Neuroscience Abstracts. 37: 840.19.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  45. ^ Franzen F., Gross H. (June 1965). "Tryptamine, N,N-dimethyltryptamine, N,N-dimethyl-5-hydroxytryptamine and 5-methoxytryptamine in human blood and urine". Nature. 206 (988): 1052. doi:10.1038/2061052a0. PMID 5839067. After the elaboration of sufficiently selective and quantitative procedures, which are discussed elsewhere, we were able to study the occurrence of tryptamine, N,N-dimethyltryptamine, N,N-dimethyl-5-hydroxytryptamine and 5-hydroxytryptamine in normal human blood and urine. (...) In 11 of 37 probands N,N-dimethyltryptamine was demonstrated in blood (...). In the urine 42·95 ± 8·6 μg of dimethyltryptamine/24 h were excreted.
  46. ^ Siegel M. (October 1965). "A sensitive method for the detection of N,N-dimethylserotonin (bufotenin) in urine; failure to demonstrate its presence in the urine of schizophrenic and normal subjects". Journal of Psychiatric Research. 3 (3): 205–11. doi:10.1016/0022-3956(65)90030-0. PMID 5860629.
  47. ^ Barker S.A., Littlefield-Chabaud M.A., David C. (February 2001). "Distribution of the hallucinogens N,N-dimethyltryptamine and 5-methoxy-N,N-dimethyltryptamine in rat brain following intraperitoneal injection: application of a new solid-phase extraction LC-APcI-MS-MS-isotope dilution method". Journal of Chromatography B. 751 (1): 37–47. doi:10.1016/S0378-4347(00)00442-4. PMID 11232854.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  48. ^ a b c Forsström T., Tuominen J., Karkkäinen J. (2001). "Determination of potentially hallucinogenic N-dimethylated indoleamines in human urine by HPLC/ESI-MS-MS". Scandinavian Journal of Clinical and Laboratory Investigation. 61 (7): 547–56. doi:10.1080/003655101753218319. PMID 11763413.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  49. ^ Shen H.W., Jiang X.L., Yu A.M. (April 2009). "Development of a LC-MS/MS method to analyze 5-methoxy-N,N-dimethyltryptamine and bufotenine, and application to pharmacokinetic study". Bioanalysis. 1 (1): 87–95. doi:10.4155/bio.09.7. PMC 2879651. PMID 20523750.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  50. ^ Wyatt R.J., Mandel L.R., Ahn H.S., Walker R.W., Vanden Heuvel W.J. (July 1973). "Gas chromatographic-mass spectrometric isotope dilution determination of N,N-dimethyltryptamine concentrations in normals and psychiatric patients" (PDF). Psychopharmacologia. 31 (3): 265–70. doi:10.1007/BF00422516. PMID 4517484.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  51. ^ Angrist B., Gershon S., Sathananthan G., Walker R.W., Lopez-Ramos B., Mandel L.R., Vandenheuvel W.J. (May 1976). %7CFormat PDF "Dimethyltryptamine levels in blood of schizophrenic patients and control subjects". Psychopharmacology. 47 (1): 29–32. doi:10.1007/BF00428697. PMID 803203. {{cite journal}}: Check |url= value (help)CS1 maint: multiple names: authors list (link)
  52. ^ Oon M.C., Rodnight R. (December 1977). "A gas chromatographic procedure for determining N, N-dimethyltryptamine and N-monomethyltryptamine in urine using a nitrogen detector". Biochemical Medicine. 18 (3): 410–9. doi:10.1016/0006-2944(77)90077-1. PMID 271509.
  53. ^ a b Smythies J.R., Morin R.D., Brown G.B. (June 1979). "Identification of dimethyltryptamine and O-methylbufotenin in human cerebrospinal fluid by combined gas chromatography/mass spectrometry". Biological Psychiatry. 14 (3): 549–56. PMID 289421.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  54. ^ a b Christian S.T., Harrison R., Quayle E., Pagel J., Monti J. (October 1977). "The in vitro identification of dimethyltryptamine (DMT) in mammalian brain and its characterization as a possible endogenous neuroregulatory agent". Biochemical Medicine. 18 (2): 164–83. doi:10.1016/0006-2944(77)90088-6. PMID 20877.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  55. ^ Erowid (14 February 1999). "5-MeO-DMT dosage". Erowid 5-MeO-DMT Vault. Retrieved 8 December 2010.
  56. ^ a b Kaplan J., Mandel L.R., Stillman R., Walker R.W., VandenHeuvel W.J., Gillin J.C., Wyatt R.J. (1974). "Blood and urine levels of N,N-dimethyltryptamine following administration of psychoactive dosages to human subjects" (PDF). Psychopharmacologia. 38 (3): 239–45. doi:10.1007/BF00421376. PMID 4607811.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  57. ^ a b c d Strassman R.J., Qualls C.R. (February 1994). "Dose-response study of N,N-dimethyltryptamine in humans. I. Neuroendocrine, autonomic, and cardiovascular effects". Archives of General Psychiatry. 51 (2): 85–97. doi:10.1001/archpsyc.1994.03950020009001. PMID 8297216.
  58. ^ Barker S.A., Beaton J.M., Christian S.T., Monti J.A., Morris P.E. (August 1982). "Comparison of the brain levels of N,N-dimethyltryptamine and α, α, β, β-tetradeutero-N-N-dimethyltryptamine following intraperitoneal injection. The in vivo kinetic isotope effect". Biochemical Pharmacology. 31 (15): 2513–6. doi:10.1016/0006-2952(82)90062-4. PMID 6812592.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  59. ^ Sangiah S., Gomez M.V., Domino E.F. (December 1979). "Accumulation of N,N-dimethyltryptamine in rat brain cortical slices". Biological Psychiatry. 14 (6): 925–36. PMID 41604.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  60. ^ Sitaram B.R., Lockett L., Talomsin R., Blackman G.L., McLeod W.R. (May 1987). "In vivo metabolism of 5-methoxy-N,N-dimethyltryptamine and N,N-dimethyltryptamine in the rat". Biochemical Pharmacology. 36 (9): 1509–12. doi:10.1016/0006-2952(87)90118-3. PMID 3472526.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  61. ^ Takahashi T., Takahashi K., Ido T., Yanai K., Iwata R., Ishiwata K., Nozoe S. (December 1985). "[11C]-labeling of indolealkylamine alkaloids and the comparative study of their tissue distributions". International Journal of Applied Radiation and Isotopes. 36 (12): 965–9. doi:10.1016/0020-708X(85)90257-1. PMID 3866749.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  62. ^ Yanai K., Ido T., Ishiwata K., Hatazawa J, Takahashi T., Iwata R., Matsuzawa T. (1986). "In vivo kinetics and displacement study of a carbon-11-labeled hallucinogen, N,N-(11C)dimethyltryptamine" (PDF). European Journal of Nuclear Medicine. 12 (3): 141–6. doi:10.1007/BF00276707. PMID 3489620.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  63. ^ a b Best J, Nijhout HF, Reed M (2010). "Serotonin synthesis, release and reuptake in terminals: a mathematical model". Theoretical Biology & Medical Modelling. 7: 34. doi:10.1186/1742-4682-7-34. PMC 2942809. PMID 20723248.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) Cite error: The named reference "pmid20723248" was defined multiple times with different content (see the help page).
  64. ^ a b Merrill MA, Clough RW, Jobe PC, Browning RA (September 2005). "Brainstem seizure severity regulates forebrain seizure expression in the audiogenic kindling model" (PDF). Epilepsia. 46 (9): 1380–8. doi:10.1111/j.1528-1167.2005.39404.x. PMID 16146432.{{cite journal}}: CS1 maint: multiple names: authors list (link) Cite error: The named reference "pmid16146432" was defined multiple times with different content (see the help page).
  65. ^ Callaway J.C., McKenna D.J., Grob C.S., Brito G.S., Raymon L.P., Poland R.E., Andrade E.N.; et al. (June 1999). "Pharmacokinetics of Hoasca alkaloids in healthy humans" (PDF). Journal of Ethnopharmacology. 65 (3): 243–56. doi:10.1016/S0378-8741(98)00168-8. PMID 10404423. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  66. ^ Riba J., Valle M., Urbano G., Yritia M., Morte A., Barbanoj M.J. (July 2003). "Human pharmacology of ayahuasca: subjective and cardiovascular effects, monoamine metabolite excretion, and pharmacokinetics" (PDF). Journal of Pharmacology and Experimental Therapeutics. 306 (1): 73–83. doi:10.1124/jpet.103.049882. PMID 12660312.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  67. ^ a b c d e f g h i j k l Keiser M.J., Setola V., Irwin J.J., Laggner C., Abbas A.I., Hufeisen S.J., Jensen N.H.; et al. (November 2009). "Predicting new molecular targets for known drugs". Nature. 462 (7270): 175–81. doi:10.1038/nature08506. PMC 2784146. PMID 19881490. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  68. ^ a b Deliganis A.V., Pierce P.A., Peroutka S.J. (June 1991). "Differential interactions of dimethyltryptamine (DMT) with 5-HT1A and 5-HT2 receptors". Biochemical Pharmacology. 41 (11): 1739–44. doi:10.1016/0006-2952(91)90178-8. PMID 1828347.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  69. ^ a b c d e Pierce P.A., Peroutka S.J. (1989). "Hallucinogenic drug interactions with neurotransmitter receptor binding sites in human cortex" (PDF). Psychopharmacology. 97 (1): 118–22. doi:10.1007/BF00443425. PMID 2540505.
  70. ^ a b c d e f g h i j k l Ray T.S. (2010). Manzoni, Olivier Jacques (ed.). "Psychedelics and the Human Receptorome". PLoS ONE. 5 (2): e9019. doi:10.1371/journal.pone.0009019. PMC 2814854. PMID 20126400.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  71. ^ a b c d e Smith R.L., Canton H., Barrett R.J., Sanders-Bush E. (November 1998). "Agonist properties of N,N-dimethyltryptamine at serotonin 5-HT2A and 5-HT2C receptors" (PDF). Pharmacology, Biochemistry, and Behavior. 61 (3): 323–30. doi:10.1016/S0091-3057(98)00110-5. PMID 9768567.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  72. ^ Rothman R.B., Baumann M.H. (May 2009). "Serotonergic Drugs and Valvular Heart Disease" (PDF). Expert Opinion on Drug Safety. 8 (3): 317–29. doi:10.1517/14740330902931524. PMC 2695569. PMID 19505264.
  73. ^ Roth B.L. (January 2007). "Drugs and valvular heart disease". New England Journal of Medicine. 356 (1): 6–9. doi:10.1056/NEJMp068265. PMID 17202450.
  74. ^ Jonathan D. Urban, William P. Clarke, Mark von Zastrow, David E. Nichols, Brian Kobilka, Harel Weinstein, Jonathan A. Javitch, Bryan L. Roth, Arthur Christopoulos, Patrick M. Sexton, Keith J. Miller, Michael Spedding and Richard B. Mailman (2006-06-27). "Functional Selectivity and Classical Concepts of Quantitative Pharmacology". JPET. 320 (1): 1–13. doi:10.1124/jpet.106.104463. PMID 16803859.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  75. ^ a b c Fontanilla D., Johannessen M., Hajipour A.R., Cozzi N.V., Jackson M.B., Ruoho A.E. (February 2009). "The Hallucinogen N,N-Dimethyltryptamine (DMT) Is an Endogenous Sigma-1 Receptor Regulator". Science. 323 (5916): 934–7. doi:10.1126/science.1166127. PMC 2947205. PMID 19213917.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  76. ^ a b Cozzi N.V., Gopalakrishnan A., Anderson L.L., Feih J.T., Shulgin A.T., Daley P.F., Ruoho A.E. (December 2009). "Dimethyltryptamine and other hallucinogenic tryptamines exhibit substrate behavior at the serotonin uptake transporter and the vesicle monoamine transporter" (PDF). Journal of Neural Transmission. 116 (12): 1591–9. doi:10.1007/s00702-009-0308-8. PMID 19756361.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  77. ^ Glennon, R.A. (1994). "Classical hallucinogens: an introductory overview". In Lin, G.C.; Glennon, R.A. (eds.). Hallucinogens: An Update (PDF). NIDA Research Monograph Series. Vol. 146. Rockville, MD: U.S. Dept. of Health and Human Services, Public Health Service, National Institutes of Health, National Institute on Drug Abuse. p. 4.
  78. ^ Fantegrossi W.E., Murnane K.S., Reissig C.J. (January 2008). "The behavioral pharmacology of hallucinogens" (PDF). Biochemical Pharmacology. 75 (1): 17–33. doi:10.1016/j.bcp.2007.07.018. PMC 2247373. PMID 17977517.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  79. ^ a b c Nichols D.E. (February 2004). "Hallucinogens". Pharmacology & Therapeutics. 101 (2): 131–81. doi:10.1016/j.pharmthera.2003.11.002. PMID 14761703.
  80. ^ Vollenweider F.X., Vollenweider-Scherpenhuyzen M.F., Bäbler A., Vogel H., Hell D. (December 1998). "Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action". NeuroReport. 9 (17): 3897–902. doi:10.1097/00001756-199812010-00024. PMID 9875725.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  81. ^ a b Strassman R.J. (1996). "Human psychopharmacology of N,N-dimethyltryptamine" (PDF). Behavioural Brain Research. 73 (1–2): 121–4. doi:10.1016/0166-4328(96)00081-2. PMID 8788488.
  82. ^ Glennon R.A., Titeler M., McKenney J.D. (December 1984). "Evidence for 5-HT2 involvement in the mechanism of action of hallucinogenic agents". Life Sciences. 35 (25): 2505–11. doi:10.1016/0024-3205(84)90436-3. PMID 6513725.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  83. ^ Roth B.L., Choudhary M.S., Khan N., Uluer A.Z. (February 1997). "High-affinity agonist binding is not sufficient for agonist efficacy at 5-hydroxytryptamine2A receptors: evidence in favor of a modified ternary complex model" (PDF). Journal of Pharmacology and Experimental Therapeutics. 280 (2): 576–83. PMID 9023266.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  84. ^ Canal C.E., Olaghere da Silva U.B., Gresch P.J., Watt E.E., Sanders-Bush E., Airey D.C. (April 2010). "The serotonin 2C receptor potently modulates the head-twitch response in mice induced by a phenethylamine hallucinogen" (PDF). Psychopharmacology. 209 (2): 163–74. doi:10.1007/s00213-010-1784-0. PMC 2868321. PMID 20165943.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  85. ^ a b Su T.P., Hayashi T., Vaupel D.B. (2009). "When the Endogenous Hallucinogenic Trace Amine N,N-Dimethyltryptamine Meets the Sigma-1 Receptor" (PDF). Science Signaling. 2 (61): pe12. doi:10.1126/scisignal.261pe12. PMC 3155724. PMID 19278957.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  86. ^ Morinan A., Collier J.G. (1981). "Effects of pargyline and SKF-525A on brain N,N-dimethyltryptamine concentrations and hyperactivity in mice". Psychopharmacology. 75 (2): 179–83. doi:10.1007/BF00432184. PMID 6798607.
  87. ^ Bruns D., Riedel D., Klingauf J., Jahn R. (October 2000). "Quantal release of serotonin". Neuron. 28 (1): 205–20. doi:10.1016/S0896-6273(00)00097-0. PMID 11086995.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  88. ^ a b c Torres, Constantino Manuel; Repke, David B. (2006). Anadenanthera: Visionary Plant Of Ancient South America. Binghamton, NY: Haworth Herbal. pp. 107–122. ISBN 978-0-7890-2642-2.
  89. ^ Rivier, Laurent; Lindgren, Jan-Erik (1972). ""Ayahuasca," the South American hallucinogenic drink: An ethnobotanical and chemical investigation". Economic Botany. 26 (2): 101–129. doi:10.1007/BF02860772. ISSN 0013-0001.
  90. ^ McKenna, Dennis J.; Towers, G.H.N.; Abbott, F. (1984). "Monoamine oxidase inhibitors in South American hallucinogenic plants: Tryptamine and β-carboline constituents of Ayahuasca". Journal of Ethnopharmacology. 10 (2): 195–223. doi:10.1016/0378-8741(84)90003-5. ISSN 0378-8741. PMID 6587171.
  91. ^ Ott J. (2001). "Pharmañopo-psychonautics: human intranasal, sublingual, intrarectal, pulmonary and oral pharmacology of bufotenine" (PDF). Journal of Psychoactive Drugs. 33 (3): 273–81. doi:10.1080/02791072.2001.10400574. PMID 11718320.
  92. ^ Ayahuasca: Hallucinogens, Consciousness and the Spirit of Nature. ISBN 978-1-56025-160-6. {{cite book}}: |editor1-first= missing |editor1-last= (help)
  93. ^ The Invisible Landscape: Mind, Hallucinogens and the I Ching Terence McKenna, 1975
  94. ^ a b Rick Strassman (2001). Dmt: the Spirit Molecule: A Doctor's Revolutionary Research into the Biology of near-Death and Mystical Experiences. pp. 187–8, also pp.173–4. ISBN 978-0-89281-927-0. I had expected to hear about some of these types of experiences once we began giving DMT. I was familiar with Terence McKenna's tales of the "self-transforming machine elves" he encountered after smoking high doses of the drug. Interviews conducted with twenty experienced DMT smokers before beginning the New Mexico research also yielded some tales of similar meetings. Since most of these people were from California, I admittedly chalked up these stories to some kind of West Coast eccentricity
  95. ^ Lyttle, Thomas (1991). Psychedelic Monographs and Essays Volume 5. P M & E PUBLISHING.
  96. ^ Evans-Wentz, Walter (1990). The Fairy-Faith in Celtic Countries. New Page Books. ISBN 1-56414-708-8.
  97. ^ Haroz, Rachel; Greenberg, Michael I. (November 2005). "Emerging Drugs of Abuse". Medical Clinics of North America. 89 (6). Philadelphia: Saunders: 1259–76. doi:10.1016/j.mcna.2005.06.008. ISSN 0025-7125. OCLC 610327022. PMID 16227062. Use of DMT was first encountered in the United States in the 1960s, when it was known as a "businessman's trip" because of the rapid onset of action when smoked (2 to 5 minutes) and short duration of action (20 minutes to 1 hour).
  98. ^ a b Callaway, James C.; Grob, Charles S. (1998). "Ayahuasca Preparations and Serotonin Reuptake Inhibitors: A Potential Combination for Severe Adverse Interactions" (PDF). Journal of Psychoactive Drugs. 30 (4): 367–9. doi:10.1080/02791072.1998.10399712. ISSN 0279-1072. PMID 9924842.
  99. ^ Bergström, Mats; Westerberg, Göran; Långström, Bengt (1997). "11C-harmine as a tracer for monoamine oxidase A (MAO-A): In vitro and in vivo studies". Nuclear Medicine and Biology. 24 (4): 287–293. doi:10.1016/S0969-8051(97)00013-9. ISSN 0969-8051. PMID 9257326.
  100. ^ Andritzky, Walter (1989). "Sociopsychotherapeutic Functions of Ayahuasca Healing in Amazonia". Journal of Psychoactive Drugs. 21 (1): 77–89. doi:10.1080/02791072.1989.10472145. ISSN 0279-1072. PMID 2656954. Archived from the original on 26 February 2008. Retrieved 10 April 2012. {{cite journal}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  101. ^ "2C-B, DMT, You and Me". Maps. Retrieved 2007-01-13.
  102. ^ "Entheogens & Visionary Medicine Pages". Miqel.com. Retrieved 2007-08-17.
  103. ^ Callaway JC, Raymon LP, Hearn WL, et al. Quantitation of N,N-dimethyltryptamine and harmala alkaloids in human plasma after oral dosing with ayahuasca (1996). "Quantitation of N,N-dimethyltryptamine and harmala alkaloids in human plasma after oral dosing with ayahuasca". J. Anal. Toxicol. 20 (6): 492–497. doi:10.1093/jat/20.6.492. PMID 8889686.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  104. ^ R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 9th edition, Biomedical Publications, Seal Beach, CA, 2011, pp. 525–526.
  105. ^ Robert S. Gable (2007). "Risk assessment of ritual use of oral dimethyltryptamine (DMT) and harmala alkaloids". Addiction. 102 (1): 24–34. doi:10.1111/j.1360-0443.2006.01652.x. PMID 17207120.
  106. ^ "DMT: The psychedelic drug 'produced in your brain'". SBS. 8 November 2013. Retrieved 27 March 2014.
  107. ^ Wallach J V (2009). "Endogenous hallucinogens as ligands of the trace amine receptors: a possible role in sensory perception". Med Hypotheses. 72 (1): 91–4. doi:10.1016/j.mehy.2008.07.052. PMID 18805646.
  108. ^ "The God Chemical: Brain Chemistry And Mysticism". NPR. Retrieved 2012-09-20.
  109. ^ Callaway J (1988). "A proposed mechanism for the visions of dream sleep". Med Hypotheses. 26 (2): 119–24. doi:10.1016/0306-9877(88)90064-3. PMID 3412201.
  110. ^ Wallach J V (2009). "Endogenous hallucinogens as ligands of the trace amine receptors: a possible role in sensory perception". Med Hypotheses. 72 (1): 91–4. doi:10.1016/j.mehy.2008.07.052. PMID 18805646.
  111. ^ Hoffer A., Osmond H., Smythies J. (January 1954). "Schizophrenia; a new approach. II. Result of a year's research". Journal of Mental Science. 100 (418): 29–45. doi:10.1192/bjp.100.418.29. PMID 13152519.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  112. ^ Schaepe, Herbert (2001). "International control of the preparation "ayahuasca"" (JPG). Erowid. Retrieved November 29, 2010. {{cite web}}: Cite has empty unknown parameter: |month= (help)
  113. ^ "Consultation on implementation of model drug schedules for Commonwealth serious drug offences". Australian Government, Attorney-General’s Department. 24 June 2010.
  114. ^ http://connection.ebscohost.com/c/articles/79564875/aussie-dmt-ban
  115. ^ Berry, Michael; NZPA (19 May 2011). "Rare drug bound for Blenheim". Malborough Express. Blenheim, New Zealand: Fairfax New Zealand. Retrieved 23 May 2012.
  116. ^ "Schedule 1: Class A controlled drugs". Misuse of Drugs Act 1975. Wellington, N.Z.: Parliamentary Counsel Office/Te Tari Tohutohu Pāremata. 1 May 2012. Retrieved 23 May 2012.
  117. ^ Church of the Holy Light of the Queen v. Mukasey
  118. ^ Church of the Holy Light of the Queen v. Mukasey (D. Ore. 2009) ("permanently enjoins Defendants from prohibiting or penalizing the sacramental use of Daime tea by Plaintiffs during Plaintiffs' religious ceremonies"), Text.

External links

Retrieved from "https://en.wikipedia.org/w/index.php?title=N,N-Dimethyltryptamine&oldid=620716339"