N,N-Dimethyltryptamine

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
IUPAC name
  • 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 mass188.274 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]
SMILES
  • CN(CCC1=CNC2=C1C=CC=C2)C
InChI
  • 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
  (verify)

N,N-Dimethyltryptamine (DMT or N,N-DMT) is a substituted tryptamine that occurs in many plants and animals and which is both a derivative and a structural analog of tryptamine.[3] It is used as a recreational psychedelic drug and prepared by various cultures for ritual purposes as an entheogen.[4]

DMT has a rapid onset, intense effects, and a relatively short duration of action. For those reasons, DMT was known as the "business trip" during the 1960s in the United States, as a user could access the full depth of a psychedelic experience in considerably less time than with other substances such as LSD or psilocybin mushrooms.[5] DMT can be inhaled, ingested, or injected and its effects depend on the dose, as well as the mode of administration. When inhaled or injected, the effects last a short period of time: about five to 15 minutes. Effects can last three hours or more when orally ingested along with a monoamine oxidase inhibitor (MAOI), such as the ayahuasca brew of many native Amazonian tribes.[6] DMT can produce vivid "projections" of mystical experiences involving euphoria and dynamic hallucinations of geometric forms.[7]

DMT is a functional analog and structural analog of other psychedelic tryptamines such as O-acetylpsilocin (4-AcO-DMT), 5-MeO-DMT, psilocybin (4-PO-DMT), psilocin (4-HO-DMT), and bufotenin (5-HO-DMT). The structure of DMT occurs within some important biomolecules like serotonin and melatonin, making them structural analogs of DMT.

Human consumption

DMT is produced in many species of plants often in conjunction with its close chemical relatives 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and bufotenin (5-OH-DMT).[8] DMT-containing plants are commonly used in indigenous Amazonian shamanic practices. It is usually one of the main active constituents of the drink ayahuasca;[9][4] 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.[8] 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.[8][10] Psilocin and its precursor psilocybin, an active chemical in many psilocybin mushrooms, are structurally similar to DMT.

The psychotropic effects of DMT were first studied scientifically by the Hungarian chemist and psychologist Stephen Szára, who performed research with volunteers in the mid-1950s. Szára, who later worked for the United States National Institutes of Health, 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.[11]

DMT is generally not active orally unless it is combined with a monoamine oxidase inhibitor such as a reversible inhibitor of monoamine oxidase A (RIMA), for example, harmaline.[4] Without a MAOI, the body quickly metabolizes orally administered DMT, and it therefore has no hallucinogenic effect unless the dose exceeds the body's monoamine oxidase's metabolic capacity. Other means of 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 an MAOI prior to vaporizing or injecting DMT prolongs and potentiates the effects.[7]

Clinical use research

Dimethyltryptamine (DMT), an endogenous ligand of sigma-1 receptors (Sig-1Rs), acts against systemic hypoxia. Research demonstrates DMT reduces the number of apoptotic and ferroptotic cells in mammalian forebrain and supports astrocyte survival in an ischemic environment. According to these data, DMT may be considered as adjuvant pharmacological therapy in the management of acute cerebral ischemia.[12]

Neuropharmocology

Quantities of dimethyltryptamine and O-methyl-bufotenine were found present in the cerebrospinal fluid of humans in a psychiatric study.[13]

Effects

Subjective psychedelic experiences

Induced DMT experiences can include profound time-dilation, visual, auditory, tactile, and proprioceptive distortions and hallucinations, and other experiences that, by most firsthand accounts, defy verbal or visual description.[14] Examples include perceiving hyperbolic geometry or seeing Escher-like impossible objects.[15]

Several scientific experimental studies have tried to measure subjective experiences of altered states of consciousness induced by drugs under highly controlled and safe conditions.

Rick Strassman and his colleagues conducted a five-year-long DMT study at the University of New Mexico in the 1990s.[16] The results provided insight about the quality of subjective psychedelic experiences. In this study participants received the DMT dosage via intravenous injection and the findings suggested that different psychedelic experiences can occur, depending on the level of dosage. Lower doses (0.01 and 0.05 mg/kg) produced somaesthetic and emotional responses, but not hallucinogenic experiences (e.g., 0.05 mg/kg had mild mood elevating and calming properties).[16] In contrast, responses produced by higher doses (0.2 and 0.4 mg/kg) researchers labeled as "hallucinogenic" that elicited "intensely colored, rapidly moving display of visual images, formed, abstract or both". Comparing to other sensory modalities the most affected was the visual. Participants reported visual hallucinations, fewer auditory hallucinations and specific physical sensations progressing to a sense of bodily dissociation, as well as to experiences of euphoria, calm, fear, and anxiety.[16] These dose-dependent effects match well with anonymously posted "trip reports" online, where users report "breakthroughs" above certain doses.[17][18][19] These "breakthrough" experiences often result with the user becoming completely or almost completely detached from reality (especially visually and auditorily), and thrust into "DMT hyperspace". It is here that most users report contact with entities, while even doses slightly under a breakthrough dose have far less extreme effects.

Strassman also stressed the importance of the context where the drug has been taken. He claimed that DMT has no beneficial effects of itself, rather the context when and where people take it plays an important role.[11][16]

It appears that DMT can induce a state or feeling where the person believes to "communicate with other intelligent-life forms" (see "machine elves"). High doses of DMT produce a state that involves a sense of "another intelligence" that people sometimes describe as "super-intelligent", but "emotionally detached".[16]

Machine elf / jester

A 1995 study by Adolf Dittrich and Daniel Lamparter found that the DMT-induced altered state of consciousness (ASC) is strongly influenced by habitual rather than situative factors. In the study, researchers used three dimensions of the APZ questionnaire to examine ASC. The first dimension, oceanic boundlessness (OB), refers to dissolution of ego boundaries and is mostly associated with positive emotions.[20] The second dimension, anxious ego-dissolution (AED), represents a disordering of thoughts and decreases in autonomy and self-control. Last, visionary restructuralization (VR) refers to auditory/visual illusions and hallucinations.[21] Results showed strong effects within the first and third dimensions for all conditions, especially with DMT, and suggested strong intrastability of elicited reactions independently of the condition for the OB and VR scales.[20]

Reported encounters with external entities

Entities perceived during DMT inebriation have been represented in diverse forms of psychedelic art. The term machine elf was coined by ethnobotanist Terence McKenna for the entities he encountered in DMT "hyperspace", also using terms like fractal elves, or self-transforming machine elves.[22][23] McKenna first encountered the "machine elves" after smoking DMT in Berkeley in 1965. His subsequent speculations regarding the hyperdimensional space in which they were encountered have inspired a great many artists and musicians, and the meaning of DMT entities has been a subject of considerable debate among participants in a networked cultural underground, enthused by McKenna's effusive accounts of DMT hyperspace.[24] Cliff Pickover has also written about the "machine elf" experience, in the book Sex, Drugs, Einstein, & Elves,[6] while Rick Strassman notes many similarities between self-reports of his DMT study participants' encounters with these "entities", and mythological descriptions of figures such as Chayot Ha Kodesh in ancient religions, including both angels and demons.[25] Strassman also argues for a similarity in his study participants' descriptions of mechanized wheels, gears and machinery in these encounters, with those described in visions of encounters with the Living Creatures and Ophanim of the Hebrew Bible, noting they may stem from a common neuropsychopharmacological experience.[25]

Strassman argues that the more positive of the "external entities" encountered in DMT experiences should be understood as analogous to certain forms of angels:

The medieval Jewish philosophers whom I rely upon for understanding the Hebrew Bible text and its concept of prophecy portray angels as God's intermediaries. That is, they perform a certain function for God. Within the context of my DMT research, I believe that the beings that volunteers see could be conceived of as angelic - that is, previously invisible, incorporeal spiritual forces that are engarbed or enclothed in a particular form - determined by the psychological and spiritual development of the volunteers - bringing a particular message or experience to that volunteer.[26]

However, Strassman's experimental participants also note that some other entities can subjectively resemble creatures more like insects and aliens.[27] As a result, Strassman writes these experiences among his experimental participants "also left me feeling confused and concerned about where the spirit molecule was leading us. It was at this point that I began to wonder if I was getting in over my head with this research."[28]

Hallucinations of strange creatures had been reported by Stephen Szara in a 1958 study in psychotic patients, in which he described how one of his subjects under the influence of DMT had experienced "strange creatures, dwarves or something" at the beginning of a DMT trip.[29][30]

Other researchers of the entities seemingly encountered by DMT users describe them as "entities" or "beings" in humanoid as well as animal form, with descriptions of "little people" being common (non-human gnomes, elves, imps, etc.).[31] Strassman and others have speculated that this form of hallucination may be the cause of alien abduction and extraterrestrial encounter experiences, which may occur through endogenously-occurring DMT.[32][33]

Likening them to descriptions of rattling and chattering auditory phenomenon described in encounters with the Hayyoth in the Book of Ezekiel, Rick Strassman notes that participants in his studies, when reporting encounters with the alleged entities, have also described loud auditory hallucinations, such as one subject reporting typically "the elves laughing or talking at high volume, chattering, twittering".[25]

Near-death experience

A 2018 study found significant relationships between a DMT experience and a near-death experience.[34] A 2019 large-scale study found that ketamine, Salvia divinorum, and DMT (and other classical psychedelic substances) are linked to near-death experiences.[35]

Physiological response

According to a dose-response study in human subjects, dimethyltryptamine administered intravenously 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 rise equally in response to all doses of DMT, and melatonin levels were unaffected."[16]

Dependence liability

The dependence potential of DMT and the risk of sustained psychological disturbance may be minimal when used infrequently, as in religious ceremonies; however, the physiological dependence potential of DMT and ayahuasca has not yet been documented convincingly.[36]

Conjecture regarding endogenous effects

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.[37] 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.[38] DMT is naturally occurring in small amounts in rat brain, human cerebrospinal fluid, and other tissues of humans and other mammals.[39][40][41][42] Further, mRNA for the enzyme necessary for the production of DMT, INMT, are expressed in the human cerebral cortex, choroid plexus, and pineal gland, suggesting an endogenous role in the human brain.[43] In 2011, Nicholas V. Cozzi, of the University of Wisconsin School of Medicine and Public Health, concluded that INMT, an enzyme that is 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] Neurobiologist Andrew Gallimore (2013) suggested that while DMT might not have a modern neural function, it may have been an ancestral neuromodulator once secreted in psychedelic concentrations during REM sleep, a function now lost.[31]

Routes of administration

Inhalation

A standard dose for vaporized DMT is 20–60 milligrams, depending highly on the efficiency of vaporization as well as body weight and personal variation.[45] In general, this is inhaled in a few successive breaths, but lower doses can be used if the user can inhale it in fewer breaths (ideally one). 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 "business trip" in the US because of the relatively short duration (and rapid onset) of action when inhaled.[46] DMT can be inhaled using a bong, typically when sandwiched between layers of plant matter, using a specially designed pipe, or by using an e-cigarette once it has been dissolved in propylene glycol or vegetable glycerin.[47] Some users have also started using vaporizers meant for cannabis extracts ("wax pens") for ease of temperature control when vaporizing crystals. A DMT-infused smoking blend is called Changa, and is typically used in pipes or other utensils meant for smoking dried plant matter.

Injection

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 that the subjects reported visiting while under the influence of DMT.[11]

Oral ingestion

Ayahuasca preparation

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).[4] 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.[4] The Ayahuasca vine contains harmala alkaloids,[48] highly active reversible inihibitors of monoamine oxidase A (RIMAs),[49] rendering the DMT orally active by protecting it from deamination.[4] A variety of different recipes are used to make the brew depending on the purpose of the ayahuasca session,[50] 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 but also contain gramine, which is toxic and difficult to separate. 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.

Taken orally with an RIMA, DMT produces a long lasting (over three hour), slow, deep metaphysical experience similar to that of psilocybin mushrooms, but more intense.[51] RIMAs should be used with caution as they can have fatal interactions with some prescription drugs such as SSRI antidepressants, and some over-the-counter drugs known as sympathomimetics such as Ephedrine or certain cough medicines and even some herbal remedies .[48]

History

Naturally occurring substances (of both vegetable and animal origin) containing DMT have been used in South America since pre-Columbian times.[52][53]

DMT was first synthesized in 1931 by chemist Richard Helmuth Fredrick Manske (born 1901 in Berlin, Germany – 1977).[54][55] 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.[55][11][56] 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.[57] 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.[57][58] 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).[57][59] Since 1955, DMT has been found in a host of organisms: in at least fifty plant species belonging to ten families,[60] and in at least four animal species, including one gorgonian[61] and three mammalian species (including humans).

In terms of a scientific understanding, the hallucinogenic properties of DMT were not uncovered until 1956 by Hungarian chemist and psychiatrist Stephen Szara. In his paper “Dimethyltryptamin: Its Metabolism in Man; the Relation of its Psychotic Effect to the Serotonin Metabolism”, Szara employed synthetic DMT, synthesized by the method of Speeter and Anthony, which was then administered to 20 volunteers by intramuscular injection. Urine samples were collected from these volunteers for the identification of DMT metabolites.[62] This is considered to be the converging link between the chemical structure DMT to its cultural consumption as a psychoactive and religious sacrament.[63]

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.[64] 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.[65][66] The mistake likely led the writer William Burroughs to regard the DMT he experimented with in Tangier in 1961 as "Prestonia".[67] 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).[66] Published in 1970, the first identification of DMT in the plant Psychotria viridis,[56] another common additive of ayahuasca, was made by a team of American researchers led by pharmacologist Ara der Marderosian.[68] Not only did they detect DMT in leaves of P. viridis obtained from Kaxinawá indigenous people, but they also were the first to identify it in a sample of an ayahuasca decoction, prepared by the same indigenous people.[56]

International law

By country and continent

Asia

  • Israel – DMT is an illegal substance; production, trade and possession are prosecuted as crimes.[69]
  • India – DMT is completely illegal to produce, transport, trade in or possess.[70]

Europe

  • France – DMT, along with most of its plant sources, is classified as a stupéfiant (narcotic).
  • Germany – DMT is prohibited as a class I drug.[71]
  • Republic of Ireland – DMT is an illegal Schedule 1 drug under the Misuse of Drugs Acts.[72] An attempt in 2014 by a member of the Santo Daime church to gain a religious exemption to import the drug failed.[73]
  • Latvia — DMT is prohibited as a Schedule I drug.[74][75]
  • Netherlands – The drug is banned as it is classified as a List 1 Drug per the Opium Law. Production, trade and possession of DMT are prohibited.
  • Russia – Classified as a Schedule I narcotic, including its derivatives (see sumatriptan and zolmitriptan).[76]
  • Serbia – DMT, along with stereoisomers and salts is classified as List 4 (Psychotropic substances) substance according to Act on Control of Psychoactive Substances.
  • Sweden - DMT is considered a Schedule 1 drug. The Swedish supreme court concluded in 2018 that possession of processed plant material containing a significant amount of DMT is illegal. However, possession of unprocessed such plant material was ruled legal.[77][78]
  • United Kingdom – DMT is classified as a Class A drug.
  • Belgium - DMT cannot be possessed, sold, purchased or imported. Usage is not specifically prohibited, but since usage implies possession one could be prosecuted that way.[79]

North America

  • Canada – DMT is classified as a Schedule III drug under the Controlled Drugs and Substances Act, but is legal for religious groups to use.[80]

In 2017 the Santo Daime Church Céu do Montréal received religious exemption to use Ayahuasca as a sacrament in their rituals.[81]

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 Espírita Beneficente União do Vegetal, the Supreme Court heard arguments on 1 November 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,[82] presided over by Judge Owen M. Panner, was ruled in favor of the Santo Daime church. As of 21 March 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.[83]

Oceania

  • New Zealand – DMT is classified as a Class A drug under the Misuse of Drugs Act 1975.[84][85]
  • Australia – DMT is listed as a Schedule 9 prohibited substance in Australia under the Poisons Standard (October 2015).[86] A schedule 9 drug is outlined in the Poisons Act 1964 as "Substances which may be abused or misused, the manufacture, possession, sale or use of which should be prohibited by law except when required for medical or scientific research, or for analytical, teaching or training purposes with approval of the CEO."[87] 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".[88] 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 people).[89] Under the Misuse of Drugs act 1981 6.0 g of DMT is considered enough to determine a court of trial and 2.0 g is considered intent to sell and supply.[90]

Chemistry

DMT crystals

DMT is commonly handled and stored as a fumarate,[91] as other DMT acid salts are extremely 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 as it has a lower boiling point.[91]

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 adjacent picture. 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).[92][93] 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,[94][95][96] and DMT[94][96] 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.[92][94][96][97][98]

Laboratory synthesis

DMT can be synthesized through several possible pathways from different starting materials. The two most commonly encountered synthetic routes are through the reaction of indole with oxalyl chloride followed by reaction with dimethylamine and reduction of the carbonyl functionalities with lithium aluminum hydride to form DMT.[99] The second commonly encountered route is through the n,n-dimethylation of tryptamine using formaldehyde followed by reduction with sodium cyanoborohydride or sodium triacetoxyborohydride. Sodium borohydride can be used but requires a larger excess of reagents and lower temperatures due to it having a higher selectivity for carbonyl groups as opposed to imines.[100] Procedures using sodium cyanoborohydride and sodium triacetoxyborohydride (presumably created in situ from cyanoborohydride though this may not be the case due to the presence of water and/or methanol) also result in the creation of cyanated tryptamine and beta-carboline by-products of unknown toxicity while using sodium borohydride in absence of acid does not.[101] Bufotenine, a plant extract, can also be synthesized into DMT.[102] Alternatively methyl iodide can be used but this results in the creation of a quaternary ammonium salt which must be transformed back into a tertiary amine.

Clandestine manufacture

DMT during various stages of purification

In a clandestine setting, DMT is not typically synthesized due to the lack of availability of the starting materials, namely tryptamine and oxalyl chloride. Instead, it is more often extracted from plant sources using a non-polar hydrocarbon solvent such as naphtha or heptane, and a base such as sodium hydroxide.

Alternatively, an acid-base extraction is sometimes used instead.

A variety of plants contain DMT at sufficient levels for being viable sources,[103] but specific plants such as Mimosa tenuiflora and Acacia confusa are most often used.

The chemicals involved in the extraction are commonly available. The plant material may be illegal to procure in some countries. The end product (DMT) is illegal in most countries.

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.[92] This finding initiated a still ongoing scientific interest in endogenous DMT production in humans and other mammals.[93][39] 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.[93]

In 2013, researchers reported DMT in the pineal gland microdialysate of rodents.[104]

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.[105] It is assumed that more than half of the amount of DMT produced by the acidophilic cells of the pineal gland is secreted before and during death, the amount being 0.0025-0.0034 g/kg. However, this claim by Strassman has been criticized by David Nichols who notes that DMT does not appear to be produced in any meaningful amount by the pineal gland. Removal or calcification of the pineal gland does not induce any of the symptoms caused by removal of DMT. The symptoms presented are consistent solely with reduction in melatonin, which is the pineal gland's known function. Nichols instead suggests that dynorphin and other endorphins are responsible for the reported euphoria experienced by patients during a near-death experience.[106] In 2014, researchers demonstrated the immunomodulatory potential of DMT and 5-MeO-DMT through the Sigma-1 receptor of human immune cells. This immunomodulatory activity may contribute to significant anti-inflammatory effects and tissue regeneration.[107]

Endogenous DMT

N,N-dimethyltryptamine (DMT), a psychedelic compound identified endogenously in mammals, is biosynthesized by aromatic-L-amino acid decarboxylase (AADC) and indolethylamine-N-methyltransferase (INMT). Studies have investigated brain expression of INMT transcript in rats and humans, co-expression of INMT and AADC mRNA in rat brain and periphery, and brain concentrations of DMT in rats. INMT transcripts were identified in the cerebral cortex, pineal gland, and choroid plexus of both rats and humans via in situ hybridization. Notably, INMT mRNA was colocalized with AADC transcript in rat brain tissues, in contrast to rat peripheral tissues where there existed little overlapping expression of INMT with AADC transcripts. Additionally, extracellular concentrations of DMT in the cerebral cortex of normal behaving rats, with or without the pineal gland, were similar to those of canonical monoamine neurotransmitters including serotonin. A significant increase of DMT levels in the rat visual cortex was observed following induction of experimental cardiac arrest, a finding independent of an intact pineal gland. These results show for the first time that the rat brain is capable of synthesizing and releasing DMT at concentrations comparable to known monoamine neurotransmitters and raise the possibility that this phenomenon may occur similarly in human brains.[108]

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-HO-DMT), in human blood and urine.[109] In an article published four months later, the method used in their study was strongly criticized, and the credibility of their results challenged.[110]

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.[111][112] Gas chromatography, preferably coupled to mass spectrometry (GC-MS), is considered a minimum requirement.[112] A study published in 2005[39] implements the most sensitive and selective method ever used to measure endogenous DMT:[113] liquid chromatography-tandem mass spectrometry with electrospray ionization (LC-ESI-MS/MS) allows for reaching limits of detection (LODs) 12 to 200 fold lower than those attained by the best methods employed in the 1970s. The data summarized in the table below are from studies conforming to the abovementioned requirements (abbreviations used: CSF = cerebrospinal fluid; LOD = limit of detection; n = number of samples; ng/L and ng/kg = nanograms (10−9 g) per litre, and nanograms per kilogram, respectively):

DMT in body fluids and tissues (NB: units have been harmonized)
Species Sample Results
Human Blood serum < LOD (n = 66)[39]
Blood plasma < LOD (n = 71)[39]  ♦  < LOD (n = 38); 1,000 & 10,600 ng/L (n = 2)[114]
Whole blood < LOD (n = 20); 50–790 ng/L (n = 20)[115]
Urine < 100 ng/L (n = 9)[39]  ♦  < LOD (n = 60); 160–540 ng/L (n = 5)[112]  ♦  Detected in n = 10 by GC-MS[116]
Feces < 50 ng/kg (n = 12); 130 ng/kg (n = 1)[39]
Kidney 15 ng/kg (n = 1)[39]
Lung 14 ng/kg (n = 1)[39]
Lumbar CSF 100,370 ng/L (n = 1); 2,330–7,210 ng/L (n = 3); 350 & 850 ng/L (n = 2)[40]
Rat Kidney 12 &16 ng/kg (n = 2)[39]
Lung 22 & 12 ng/kg (n = 2)[39]
Liver 6 & 10 ng/kg (n = 2)[39]
Brain 10 &15 ng/kg (n = 2)[39]  ♦  Measured in synaptic vesicular fraction[41]
Rabbit Liver < 10 ng/kg (n = 1)[39]

A 2013 study found DMT in microdialysate obtained from a rat's pineal gland, providing evidence of endogenous DMT in the mammalian brain.[104] In 2019 experiments showed that the rat brain is capable of synthesizing and releasing DMT. These results raise the possibility that this phenomenon may occur similarly in human brains.[43]

Detection in body fluids

DMT may be measured 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. Less than 0.1% of an oral dose is eliminated unchanged in the 24-hour urine of humans.[117][118]

INMT

Before techniques of molecular biology were used to localize indolethylamine N-methyltransferase (INMT),[96][98] 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[93] or with addition of a radiolabeled substrate like (14C)NMT to demonstrate in vivo formation.[94][97] 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.[93] 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[119][120] and human[121] 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,[93][94][122] and negligible amounts of DMT in brain tissue.[93] 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.[93] These findings are a blow for all previous claims of evidence of INMT activity and DMT biosynthesis in avian[123] and mammalian brain,[124][125] including in vivo,[126][127] as they all relied upon use of the problematic TLC methods:[93] 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.[128][129] 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".[130] Capability of the method used in this latter study to resolve DMT from tetrahydro-β-carbolines is questioned later.[94]
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.[98] Northern blot analyses reveal INMT messenger RNA (mRNA) to be highly expressed in rabbit lung,[96] and in human thyroid, adrenal gland, and lung.[98][131] Intermediate levels of expression are found in human heart, skeletal muscle, trachea, stomach, small intestine, pancreas, testis, prostate, placenta, lymph node, and spinal cord.[98][131] Low to very low levels of expression are noted in rabbit brain,[98] and human thymus, liver, spleen, kidney, colon, ovary, and bone marrow.[98][131] 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).[98][131] 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] A 2020 study using in-situ hybridization, a far more accurate tool than the northern blot analysis, found mRNA coding for INMT expressed in the human cerebral cortex, choroid plexus, and pineal gland.[43]

Pharmacology

Pharmacokinetics

DMT peak level concentrations (Cmax) measured in whole blood after intramuscular (IM) injection (0.7 mg/kg, n = 11)[132] and in plasma following intravenous (IV) administration (0.4 mg/kg, n = 10)[16] 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.[133][134][135][136][137] 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.[138][139]

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,[132] and 2 minutes in plasma after IV administration.[16] 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,[140] and 90–120 minutes,[141] respectively. The pharmacokinetics for vaporizing DMT have not been studied or reported.

Neurogenesis

In September 2020, an in vitro and in vivo study showed that DMT present in the ayahuasca infusion promotes neurogenesis.[142]

Pharmacodynamics

DMT binds non-selectively with affinities < 0.6 μM to the following serotonin receptors: 5-HT1A,[143][144][145] 5-HT1B,[143][146] 5-HT1D,[143][145][146] 5-HT2A,[143][145][146][147] 5-HT2B,[143][146] 5-HT2C,[143][146][147] 5-HT6,[143][146] and 5-HT7.[143][146] An agonist action has been determined at 5-HT1A,[144] 5-HT2A and 5-HT2C.[143][146][147] 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[146] and 0.184 μM.[143] 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.[148][149][150]

It has also been shown to possess affinity for the dopamine D1, α1-adrenergic, α2-adrenergic, imidazoline-1, and σ1 receptors.[145][146][151] Converging lines of evidence established activation of the σ1 receptor at concentrations of 50–100 μM.[152] Its efficacies at the other receptor binding sites are unclear. It has also been shown in vitro to be a substrate for the cell-surface serotonin transporter (SERT) expressed in human platelets, and the rat vesicular monoamine transporter 2 (VMAT2), which was transiently expressed in fall armyworm Sf9 cells. DMT inhibited SERT-mediated serotonin uptake into platelets at an average concentration of 4.00 ± 0.70 μM and VMAT2-mediated serotonin uptake at an average concentration of 93 ± 6.8 μM.[153]

As with other so-called "classical hallucinogens",[154] a large part of DMT psychedelic effects can be attributed to a functionally selective activation of the 5-HT2A receptor.[16][143][155][156][157][158][159] 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.[143][146][147][160] 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,[146][147] 5-HT2C is also likely implicated in DMT's overall effects.[156][161] Other receptors, such as 5-HT1A[145][156][158] σ1,[152][162] may also play a role.

In 2009, it was hypothesized that DMT may be an endogenous ligand for the σ1 receptor.[152][162] 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[163] 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,[153] 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,[138][139] the concentration of serotonin in synaptic vesicles was measured at 270 mM.[164] 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.

Binding sites Binding affinity Ki (μM)[165]
5-HT1A 0.075
5-HT2A 0.237
5-HT2C 0.424
D1 6
D2 3
D3 6.3
α1A 1.3
α2A 2.1
TAAR1 2.2
H1 0.22
SERT 6
DAT 22
NET 6.5

Society and culture

Black market

Electronic cigarette cartridges filled with DMT started to be sold on the black market in 2018.[166]

See also

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" [Trifluoracetylation of methylated derivatives of tryptamine and serotonin by different reagents: synthesis, spectroscopic characterizations, and separations by capillary-gas-chromatography]. Zeitschrift für Naturforschung B. 54 (3): 397–414. doi:10.1515/znb-1999-0319. S2CID 101000504.
  2. ↑ Corothie E, Nakano T (May 1969). "Constituents of the bark of Virola sebifera". Planta Medica. 17 (2): 184–8. doi:10.1055/s-0028-1099844. PMID 5792479.
  3. ↑ Carbonaro TM, Gatch MB (September 2016). "Neuropharmacology of N,N-dimethyltryptamine". Brain Research Bulletin. 126 (Pt 1): 74–88. doi:10.1016/j.brainresbull.2016.04.016. PMC 5048497. PMID 27126737.
  4. 1 2 3 4 5 6 McKenna DJ, Towers GH, Abbott F (April 1984). "Monoamine oxidase inhibitors in South American hallucinogenic plants: tryptamine and beta-carboline constituents of ayahuasca". Journal of Ethnopharmacology. 10 (2): 195–223. doi:10.1016/0378-8741(84)90003-5. PMID 6587171.
  5. ↑ Haroz R, Greenberg MI (November 2005). "Emerging drugs of abuse". The Medical Clinics of North America. 89 (6): 1259–76. doi:10.1016/j.mcna.2005.06.008. OCLC 610327022. PMID 16227062.
  6. 1 2 Pickover C (2005). Sex, Drugs, Einstein, and Elves: Sushi, Psychedelics, Parallel Universes, and the Quest for Transcendence. Smart Publications. ISBN 978-1-890572-17-4.
  7. 1 2 "Erowid DMT (Dimethyltryptamine) Vault". Erowid.org. Retrieved 20 September 2012.
  8. 1 2 3 Torres CM, Repke DB (2006). Anadenanthera: Visionary Plant Of Ancient South America. Binghamton, NY: Haworth Herbal. pp. 107–122. ISBN 978-0-7890-2642-2.
  9. ↑ Rivier L, Lindgren JE (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. S2CID 34669901.
  10. ↑ 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. S2CID 5877023.
  11. 1 2 3 4 Strassman RJ (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.)
  12. ↑ Szabó Í, Varga VÉ, Dvorácskó S, Farkas AE, Körmöczi T, Berkecz R, et al. (July 2021). "N,N-Dimethyltryptamine attenuates spreading depolarization and restrains neurodegeneration by sigma-1 receptor activation in the ischemic rat brain". Neuropharmacology. 192: 108612. doi:10.1016/j.neuropharm.2021.108612. PMID 34023338. S2CID 235169696.
  13. ↑ Corbett L, Christian ST, Morin RD, Benington F, Smythies JR (February 1978). "Hallucinogenic N-methylated indolealkylamines in the cerebrospinal fluid of psychiatric and control populations". The British Journal of Psychiatry. 132 (2): 139–144. doi:10.1192/bjp.132.2.139. PMID 272218. S2CID 37144421.
  14. ↑ Strassman RJ, Qualls CR, Uhlenhuth EH, Kellner R (February 1994). "Dose-response study of N,N-dimethyltryptamine in humans. II. Subjective effects and preliminary results of a new rating scale". Archives of General Psychiatry. 51 (2): 98–108. doi:10.1001/archpsyc.1994.03950020022002. PMID 8297217.
  15. ↑ Gómez Emilsson A (5 October 2019). The Hyperbolic Geometry of DMT Experiences (Speech). Harvard Science of Psychedelics Club. Harvard University, Cambridge, Massachusetts: Qualia Research Institute. Archived from the original on 2021-12-11. Retrieved 27 April 2020.
  16. 1 2 3 4 5 6 7 8 9 Strassman RJ, Qualls CR (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.
  17. ↑ "DMT - How and Why to Get Off". users.aalto.fi. Archived from the original on 2021-01-26. Retrieved 2021-03-24.
  18. ↑ St John G (2018). "The Breakthrough Experience: DMT Hyperspace and its Liminal Aesthetics". Anthropology of Consciousness. 29 (1): 57–76. doi:10.1111/anoc.12089. ISSN 1556-3537.
  19. ↑ "DMT - Erowid Exp - 'Break Through'". erowid.org. Retrieved 2021-03-24.
  20. 1 2 Lamparter D, Dittrich A (1995). "Intraindividuelle Stabilität von ABZ unter sensorischer Deprivation, N,N-Dimethyltryptamin (DMT) und Stickoxydul". Yearbook of the European College for the Study of Consciousness: 33–44.
  21. ↑ Vollenweider FX (December 2001). "Brain mechanisms of hallucinogens and entactogens". Dialogues in Clinical Neuroscience. 3 (4): 265–79. doi:10.31887/DCNS.2001.3.4/fxvollenweider. PMC 3181663. PMID 22033605.
  22. ↑ Strassman R (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 with such entities. Since most of these people were from California, I admittedly chalked up these stories to some kind of West Coast eccentricity
  23. ↑ McKenna T (1975). The Invisible Landscape: Mind, Hallucinogens and the I Ching.
  24. ↑ Graham St John (2015). Mystery School in Hyperspace: A Cultural History of DMT, North Atlantic Books / Evolver. ISBN 978-1-58394-732-6. Berkeley, CA. chapters 4, 8, and 12.
  25. 1 2 3 Strassman R (2014). DMT and the Soul of Prophecy: A New Science of Spiritual Revelation in the Hebrew Bible. Simon and Schuster. ISBN 978-1-62055-168-4.
  26. ↑ Interview: Dr. Rick Strassman / AVI SOLOMON / 6:39 AM TUE 3 May 2011
  27. ↑ Strassman R (2001). DMT: the Spirit Molecule: A Doctor's Revolutionary Research into the Biology of near-Death and Mystical Experiences. pp. 206–208. ISBN 978-0-89281-927-0.
  28. ↑ Strassman R (2001). DMT: the Spirit Molecule: A Doctor's Revolutionary Research into the Biology of near-Death and Mystical Experiences. pp. 202. ISBN 978-0-89281-927-0.
  29. ↑ Hanks MA (10 September 2010). "Causal Multiplicity: The Science Behind Schizophrenia".
  30. ↑ Gallimore AR, Luke DP (15 December 2015). "DMT research from 1956 to the edge of time" (PDF).
  31. 1 2 Gallimore, A (2013). "Evolutionary Implications of the Astonishing Psychoactive Effects of N,N-Dimethyltryptamine (DMT)". Journal of Scientific Exploration. 27 (3): 455–503.
  32. ↑ Luke DP (2011). "Discarnate entities and dimethyltryptamine (DMT): Psychopharmacology, phenomenology and ontology". Journal of the Society for Psychical Research. 75 (902): 26–42.
  33. ↑ Luke DP (2012). "Psychoactive substances and paranormal phenomena: A comprehensive review". International Journal of Transpersonal Studies. 31: 97–156. doi:10.24972/ijts.2012.31.1.97.
  34. ↑ Timmermann, Christopher; Roseman, Leor; Williams, Luke; Erritzoe, David; Martial, Charlotte; Cassol, Héléna; Laureys, Steven; Nutt, David; Carhart-Harris, Robin (2018). "DMT Models the Near-Death Experience". Frontiers in Psychology. 9: 1424. doi:10.3389/fpsyg.2018.01424. PMC 6107838. PMID 30174629.
  35. ↑ Martial, C; Cassol, H; Charland-Verville, V; Pallavicini, C; Sanz, C; Zamberlan, F; Vivot, RM; Erowid, F; Erowid, E; Laureys, S; Greyson, B; Tagliazucchi, E (March 2019). "Neurochemical models of near-death experiences: A large-scale study based on the semantic similarity of written reports". Consciousness and Cognition. 69: 52–69. doi:10.1016/j.concog.2019.01.011. hdl:2268/231971. PMID 30711788. S2CID 73432875.
  36. ↑ Gable RS (January 2007). "Risk assessment of ritual use of oral dimethyltryptamine (DMT) and harmala alkaloids" (PDF). Addiction. 102 (1): 24–34. CiteSeerX 10.1.1.655.8494. doi:10.1111/j.1360-0443.2006.01652.x. PMID 17207120. Archived from the original (PDF) on 29 December 2017. Retrieved 24 October 2017.
  37. ↑ Hoffer A, Osmond H, Smythies J (January 1954). "Schizophrenia; a new approach. II. Result of a year's research". The Journal of Mental Science. 100 (418): 29–45. doi:10.1192/bjp.100.418.29. PMID 13152519.
  38. ↑ "DMT: The psychedelic drug 'produced in your brain'". SBS. 8 November 2013. Retrieved 27 March 2014.
  39. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Kärkkäinen J, Forsström T, Tornaeus J, Wähälä K, Kiuru P, Honkanen A, et al. (April 2005). "Potentially hallucinogenic 5-hydroxytryptamine receptor ligands bufotenine and dimethyltryptamine in blood and tissues". Scandinavian Journal of Clinical and Laboratory Investigation. 65 (3): 189–99. doi:10.1080/00365510510013604. PMID 16095048. S2CID 20005294.
  40. 1 2 Smythies JR, Morin RD, Brown GB (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.
  41. 1 2 Christian ST, 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.
  42. ↑ "The God Chemical: Brain Chemistry And Mysticism". NPR.org. NPR. Retrieved 20 September 2012.
  43. 1 2 3 Dean JG, Liu T, Huff S, Sheler B, Barker SA, Strassman RJ, et al. (June 2019). "Biosynthesis and Extracellular Concentrations of N,N-dimethyltryptamine (DMT) in Mammalian Brain". Scientific Reports. 9 (1): 9333. Bibcode:2019NatSR...9.9333D. doi:10.1038/s41598-019-45812-w. PMC 6597727. PMID 31249368.
  44. 1 2 Cozzi NV, Mavlyutov TA, Thompson MA, Ruoho AE (2011). "Indolethylamine N-methyltransferase expression in primate nervous tissue" (PDF). Society for Neuroscience Abstracts. 37: 840.19. Archived from the original (PDF) on 13 September 2012. Retrieved 20 September 2012.
  45. ↑ "DMT Dosage". Erowid. Retrieved 25 June 2018.
  46. ↑ Haroz R, Greenberg MI (November 2005). "Emerging drugs of abuse". The Medical Clinics of North America. 89 (6): 1259–76. doi:10.1016/j.mcna.2005.06.008. 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).
  47. ↑ Power M (5 June 2020). "I Sell DMT Vape Pens So People Can 'Break Through' at Their Own Speed". www.vice.com. Retrieved 12 July 2020.
  48. 1 2 Callaway JC, Grob CS (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. PMID 9924842. Archived from the original (PDF) on 1 February 2012. Retrieved 10 April 2012.
  49. ↑ Bergström M, Westerberg G, Långström B (May 1997). "11C-harmine as a tracer for monoamine oxidase A (MAO-A): in vitro and in vivo studies". Nuclear Medicine and Biology. 24 (4): 287–93. doi:10.1016/S0969-8051(97)00013-9. PMID 9257326.
  50. ↑ Andritzky W (1989). "Sociopsychotherapeutic functions of ayahuasca healing in Amazonia". Journal of Psychoactive Drugs. 21 (1): 77–89. doi:10.1080/02791072.1989.10472145. PMID 2656954. Archived from the original on 26 February 2008.
  51. ↑ Salak K. "Hell and back". National Geographic Adventure.
  52. ↑ Miller MJ, Albarracin-Jordan J, Moore C, Capriles JM (June 2019). "Chemical evidence for the use of multiple psychotropic plants in a 1,000-year-old ritual bundle from South America". Proceedings of the National Academy of Sciences of the United States of America. 116 (23): 11207–11212. doi:10.1073/pnas.1902174116. PMC 6561276. PMID 31061128.
  53. ↑ Anwar Y (6 May 2019). "Ayahuasca fixings found in 1,000-year-old Andean sacred bundle". Berkeley News. Retrieved 21 May 2019.
  54. ↑ Manske R.H.F. (1931). "A synthesis of the methyltryptamines and some derivatives". Canadian Journal of Research. 5 (5): 592–600. Bibcode:1931CJRes...5..592M. doi:10.1139/cjr31-097.
  55. 1 2 Bigwood J, Ott J (November 1977). "DMT: the fifteen minute trip". Head. 2 (4): 56–61. Archived from the original on 27 January 2006. Retrieved 28 November 2010.
  56. 1 2 3 Ott J (1996). Pharmacotheon: Entheogenic Drugs, Their Plant Sources and History (2nd, densified ed.). Kennewick, WA: Natural Products. ISBN 978-0-9614234-9-0.
  57. 1 2 3 Ott J (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 978-3-86135-033-0.
  58. ↑ Pachter IJ, Zacharias DE, 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.
  59. ↑ Fish MS, Johnson NM, Horning EC (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.
  60. ↑ Ott J (1994). Ayahuasca Analogues: Pangæan Entheogens (1st ed.). Kennewick, WA, USA: Natural Products. pp. 81–3. ISBN 978-0-9614234-5-2. OCLC 32895480.
  61. ↑ Cimino G, De Stefano S (1978). "Chemistry of Mediterranean gorgonians: simple indole derivatives from Paramuricea chamaeleon". Comparative Biochemistry and Physiology C. 61 (2): 361–2. doi:10.1016/0306-4492(78)90070-9.
  62. ↑ Szara S (November 1956). "Dimethyltryptamin: its metabolism in man; the relation to its psychotic effect to the serotonin metabolism". Experientia. 12 (11): 441–2. doi:10.1007/bf02157378. PMID 13384414. S2CID 7775625.
  63. ↑ McKenna DJ, Callaway JC, Grob CS (1998). "The scientific investigation of Ayahuasca: a review of past and current research". The Heffter Review of Psychedelic Research. 1 (65–77): 195–223.
  64. ↑ Hochstein FA, Paradies AM (1957). "Alkaloids of Banisteria caapi and Prestonia amazonicum". Journal of the American Chemical Society. 79 (21): 5735–36. doi:10.1021/ja01578a041.
  65. ↑ Schultes RE, Raffauf RF (1960). "Prestonia: An Amazon narcotic or not?". Botanical Museum Leaflets, Harvard University. 19 (5): 109–122. doi:10.5962/p.168526. ISSN 0006-8098. S2CID 91123988.
  66. 1 2 Poisson J (April 1965). "Note on "Natem", A Toxic Peruvian Beverage, and ITS Alkaloids" [Note on "Natem", a toxic Peruvian beverage, and its alkaloids]. Annales Pharmaceutiques Françaises (in French). 23: 241–4. PMID 14337385.
  67. ↑ St John G (2015). Mystery School in Hyperspace: A Cultural History of DMT. Berkeley, CA.: North Atlantic Books / Evolver. p. 29. ISBN 978-1-58394-732-6.
  68. ↑ Der Marderosian AH, Kensinger KM, Chao JM, Goldstein FJ (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.
  69. ↑ Senyor E (6 August 2013). "Judge's son arrested for importing 2kg of hallucinogenic drug". Ynetnews. Tel Aviv: Yediot Ahronot. Retrieved 11 August 2017. Son of central district judge arrested for allegedly importing DMT – LSD like drug – from Holland. [...] The suspect denies the allegations against him and claims he did not know the substance was on the list of illegal drugs.
  70. ↑ "THE GOD DRUG- DMT". www.mangaloretoday.com. Retrieved 10 August 2020.
  71. ↑ "Gesetz über den Verkehr mit Betäubungsmitteln (Betäubungsmittelgesetz - BtMG) Anlage I (zu § 1 Abs. 1) (nicht verkehrsfähige Betäubungsmittel)". gesetze-im-internet.de.
  72. ↑ "Man fined for having drug used in Amazon". www.irishexaminer.com. 8 September 2017.
  73. ↑ "Sect leader spared jail for importing hallucinogenic drug for religious 'sacrament'". Independent.ie.
  74. ↑ "Noteikumi par Latvijā kontrolējamajām narkotiskajām vielām, psihotropajām vielām un prekursoriem". likumi.lv. Retrieved 13 February 2019.
  75. ↑ "Regulations Regarding Narcotic Substances, Psychotropic Substances and Precursors to be Controlled in Latvia". likumi.lv. Retrieved 13 February 2019.
  76. ↑ "Постановление Правительства РФ от 30 June 1998 N 681 "Об утверждении перечня наркотических средств, психотропных веществ и их прекурсоров, подлежащих контролю в Российской Федерации" (с изменениями и дополнениями)". base.garant.ru.
  77. ↑ "Läkemedelsverkets författningssamling" (PDF). Archived from the original (PDF) on 12 April 2018. Retrieved 22 July 2019.
  78. ↑ https://www.domstol.se/globalassets/filer/domstol/hogstadomstolen/avgoranden/20182/b-1605-18.pdf
  79. ↑ "Wetgeving rond LSD en tripmiddelen | Druglijn.be".
  80. ↑ Health Canada allows more religious groups to import psychedelic ayahuasca, https://www.ctvnews.ca/health/health-canada-allows-more-religious-groups-to-import-psychedelic-ayahuasca-1.4414145 CTV, 8 May 2019.
  81. ↑ Rochester J (17 July 2017). "How Our Santo Daime Church Received Religious Exemption to Use Ayahuasca in Canada". Chacruna. Retrieved 1 May 2019.
  82. ↑ "Church of the Holy Light of the Queen v. Mukasey" (PDF). Archived from the original (PDF) on 3 October 2011. Retrieved 5 December 2018.
  83. ↑ 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
  84. ↑ Berry M, NZPA (19 May 2011). "Rare drug bound for Blenheim". Malborough Express. Blenheim, New Zealand: Fairfax New Zealand. Retrieved 23 May 2012.
  85. ↑ "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.
  86. ↑ Poisons Standard October 2015 comlaw.gov.au
  87. ↑ "Poisons Act" (PDF). slp.wa.gov.au. 1964. Archived from the original (PDF) on 22 December 2015.
  88. ↑ "Consultation on implementation of model drug schedules for Commonwealth serious drug offenses". Australian Government, Attorney-General's Department. 24 June 2010. Archived from the original on 7 November 2011.
  89. ↑ "AUSSIE DMT BAN". American Herb Association Quarterly Newsletter. 27 (3): 14. August 2012. Archived from the original on 16 December 2014.
  90. ↑ "Misuse of Drugs Act 1981 (2015)" (PDF). slp.wa.gov.au. Archived from the original (PDF) on 22 December 2015.
  91. 1 2 "Erowid Online Books : "TIHKAL" - #6 DMT". www.erowid.org.
  92. 1 2 3 Axelrod J (August 1961). "Enzymatic formation of psychotomimetic metabolites from normally occurring compounds". Science. 134 (3475): 343. Bibcode:1961Sci...134..343A. doi:10.1126/science.134.3475.343. PMID 13685339. S2CID 39122485.
  93. 1 2 3 4 5 6 7 8 9 Rosengarten H, Friedhoff AJ (1976). "A review of recent studies of the biosynthesis and excretion of hallucinogens formed by methylation of neurotransmitters or related substances". Schizophrenia Bulletin. 2 (1): 90–105. doi:10.1093/schbul/2.1.90. PMID 779022.
  94. 1 2 3 4 5 6 Barker SA, Monti JA, Christian ST (1981). "N,N-Dimethyltryptamine: An Endogenous Hallucinogen". N, N-dimethyltryptamine: an endogenous hallucinogen. International Review of Neurobiology. Vol. 22. pp. 83–110. doi:10.1016/S0074-7742(08)60291-3. ISBN 978-0-12-366822-6. PMID 6792104.
  95. ↑ Lin RL, Narasimhachari N, Himwich HE (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.
  96. 1 2 3 4 5 Thompson MA, Weinshilboum RM (December 1998). "Rabbit lung indolethylamine N-methyltransferase. cDNA and gene cloning and characterization". The Journal of Biological Chemistry. 273 (51): 34502–10. doi:10.1074/jbc.273.51.34502. PMID 9852119.
  97. 1 2 Mandel LR, Prasad R, Lopez-Ramos B, Walker RW (January 1977). "The biosynthesis of dimethyltryptamine in vivo". Research Communications in Chemical Pathology and Pharmacology. 16 (1): 47–58. PMID 14361.
  98. 1 2 3 4 5 6 7 8 Thompson MA, Moon E, Kim UJ, Xu J, Siciliano MJ, Weinshilboum RM (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.
  99. ↑ "Erowid Online Books : "TIHKAL" - #6 DMT". erowid.org.
  100. ↑ Bosch J, Roca T, Armengol M, Fernández-Forner D (4 February 2001). "Synthesis of 5-(sulfamoylmethyl)indoles". Tetrahedron. 57 (6): 1041–1048. doi:10.1016/S0040-4020(00)01091-7.
  101. ↑ Brandt SD, Moore SA, Freeman S, Kanu AB (July 2010). "Characterization of the synthesis of N,N-dimethyltryptamine by reductive amination using gas chromatography ion trap mass spectrometry". Drug Testing and Analysis. 2 (7): 330–338. doi:10.1002/dta.142. PMID 20648523.
  102. ↑ Moreira LA, Murta MM, Gatto CC, Fagg CW, dos Santos ML (April 2015). "Concise synthesis of N,N-dimethyltryptamine and 5-methoxy-N,N-dimethyltryptamine starting with bufotenine from Brazilian Anadenanthera ssp". Natural Product Communications. 10 (4): 581–584. doi:10.1177/1934578X1501000411. PMID 25973481. S2CID 34076965.
  103. ↑ Carbonaro TM, Gatch MB (September 2016). "Neuropharmacology of N,N-dimethyltryptamine". Brain Research Bulletin. 126 (Pt 1): 74–88. doi:10.1016/j.brainresbull.2016.04.016. PMC 5048497. PMID 27126737.
  104. 1 2 Barker SA, Borjigin J, Lomnicka I, Strassman R (December 2013). "LC/MS/MS analysis of the endogenous dimethyltryptamine hallucinogens, their precursors, and major metabolites in rat pineal gland microdialysate" (PDF). Biomedical Chromatography. 27 (12): 1690–700. doi:10.1002/bmc.2981. hdl:2027.42/101767. PMID 23881860.
  105. ↑ Gomes MM, Coimbra JB, Clara RO, Dörr FA, Moreno AC, Chagas JR, et al. (April 2014). "Biosynthesis of N,N-dimethyltryptamine (DMT) in a melanoma cell line and its metabolization by peroxidases". Biochemical Pharmacology. 88 (3): 393–401. doi:10.1016/j.bcp.2014.01.035. PMID 24508833.
  106. ↑ Nichols, DE (Nov 2017). "N,N-dimethyltryptamine and the pineal gland: Separating fact from myth". Journal of Psychopharmacology. 32 (1): 30–36. doi:10.1177/0269881117736919. PMID 29095071.
  107. ↑ Szabo A, Kovacs A, Frecska E, Rajnavolgyi E (29 August 2014). "Psychedelic N,N-dimethyltryptamine and 5-methoxy-N,N-dimethyltryptamine modulate innate and adaptive inflammatory responses through the sigma-1 receptor of human monocyte-derived dendritic cells". PLOS ONE. 9 (8): e106533. Bibcode:2014PLoSO...9j6533S. doi:10.1371/journal.pone.0106533. PMC 4149582. PMID 25171370.
  108. ↑ Dean JG, Liu T, Huff S, Sheler B, Barker SA, Strassman RJ, et al. (June 2019). "Biosynthesis and Extracellular Concentrations of N,N-dimethyltryptamine (DMT) in Mammalian Brain". Scientific Reports. 9 (1): 9333. Bibcode:2019NatSR...9.9333D. doi:10.1038/s41598-019-45812-w. PMC 6597727. PMID 31249368.
  109. ↑ 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. Bibcode:1965Natur.206.1052F. doi:10.1038/2061052a0. PMID 5839067. S2CID 4226040. 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.
  110. ↑ 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.
  111. ↑ Barker SA, Littlefield-Chabaud MA, 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, Biomedical Sciences and Applications. 751 (1): 37–47. doi:10.1016/S0378-4347(00)00442-4. PMID 11232854.
  112. 1 2 3 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.
  113. ↑ Shen HW, Jiang XL, Yu AM (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.
  114. ↑ Wyatt RJ, Mandel LR, Ahn HS, Walker RW, Vanden Heuvel WJ (July 1973). "Gas chromatographic-mass spectrometric isotope dilution determination of N,N-dimethyltryptamine concentrations in normals and psychiatric patients". Psychopharmacologia. 31 (3): 265–70. doi:10.1007/BF00422516. PMID 4517484. S2CID 42469897.
  115. ↑ Angrist B, Gershon S, Sathananthan G, Walker RW, Lopez-Ramos B, Mandel LR, Vandenheuvel WJ (May 1976). "Dimethyltryptamine levels in blood of schizophrenic patients and control subjects". Psychopharmacology. 47 (1): 29–32. doi:10.1007/BF00428697. PMID 803203. S2CID 5850801.
  116. ↑ Oon MC, 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.
  117. ↑ Callaway JC, Raymon LP, Hearn WL, McKenna DJ, Grob CS, Brito GS, Mash DC (October 1996). "Quantitation of N,N-dimethyltryptamine and harmala alkaloids in human plasma after oral dosing with ayahuasca". Journal of Analytical Toxicology. 20 (6): 492–7. doi:10.1093/jat/20.6.492. PMID 8889686.
  118. ↑ R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 9th edition, Biomedical Publications, Seal Beach, CA, 2011, pp. 525–526.
  119. ↑ Mandel LR, Rosenzweig S, Kuehl FA (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.
  120. ↑ Lin R, 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.
  121. ↑ Mandel LR, Ahn HS, VandenHeuvel WJ (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.
  122. ↑ Rosengarten H, Meller E, Freidhoff AJ (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.
  123. ↑ Morgan M, Mandell AJ (August 1969). "Indole(ethyl)amine N-methyltransferase in the brain". Science. 165 (3892): 492–3. Bibcode:1969Sci...165..492M. doi:10.1126/science.165.3892.492. PMID 5793241. S2CID 43317224.
  124. ↑ Mandell AJ, Morgan M (March 1971). "Indole(ethyl)amine N-methyltransferase in human brain". Nature. 230 (11): 85–7. doi:10.1038/newbio230085a0. PMID 5279043.
  125. ↑ Saavedra JM, Coyle JT, 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. S2CID 42038762.
  126. ↑ Saavedra JM, Axelrod J (March 1972). "Psychotomimetic N-methylated tryptamines: formation in brain in vivo and in vitro" (PDF). Science. 175 (4028): 1365–6. Bibcode:1972Sci...175.1365S. doi:10.1126/science.175.4028.1365. PMID 5059565. S2CID 30864349.
  127. ↑ Wu PH, Boulton AA (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.
  128. ↑ Boarder MR, 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. S2CID 36334101.
  129. ↑ Gomes UR, Neethling AC, Shanley BC (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. S2CID 6043841.
  130. ↑ Stramentinoli G, Baldessarini RJ (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. S2CID 26099031.
  131. 1 2 3 4 "INMT - Indolethylamine N-methyltransferase - Homo sapiens (Human) - INMT gene & protein". www.uniprot.org.
  132. 1 2 Kaplan J, Mandel LR, Stillman R, Walker RW, VandenHeuvel WJ, Gillin JC, Wyatt RJ (1974). "Blood and urine levels of N,N-dimethyltryptamine following administration of psychoactive dosages to human subjects". Psychopharmacologia. 38 (3): 239–45. doi:10.1007/BF00421376. PMID 4607811. S2CID 12346844.
  133. ↑ Barker SA, Beaton JM, Christian ST, Monti JA, Morris PE (August 1982). "Comparison of the brain levels of N,N-dimethyltryptamine and alpha, alpha, beta, beta-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.
  134. ↑ Sangiah S, Gomez MV, Domino EF (December 1979). "Accumulation of N,N-dimethyltryptamine in rat brain cortical slices". Biological Psychiatry. 14 (6): 925–36. PMID 41604.
  135. ↑ Sitaram BR, Lockett L, Talomsin R, Blackman GL, McLeod WR (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.
  136. ↑ 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". The International Journal of Applied Radiation and Isotopes. 36 (12): 965–9. doi:10.1016/0020-708X(85)90257-1. PMID 3866749.
  137. ↑ 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". European Journal of Nuclear Medicine. 12 (3): 141–6. doi:10.1007/BF00276707. PMID 3489620. S2CID 20030999.
  138. 1 2 Best J, Nijhout HF, Reed M (August 2010). "Serotonin synthesis, release and reuptake in terminals: a mathematical model". Theoretical Biology & Medical Modelling. 7 (1): 34. doi:10.1186/1742-4682-7-34. PMC 2942809. PMID 20723248.
  139. 1 2 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. S2CID 23783863. Archived from the original (PDF) on 31 October 2018.
  140. ↑ Callaway JC, McKenna DJ, Grob CS, Brito GS, Raymon LP, Poland RE, 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.
  141. ↑ Riba J, Valle M, Urbano G, Yritia M, Morte A, Barbanoj MJ (July 2003). "Human pharmacology of ayahuasca: subjective and cardiovascular effects, monoamine metabolite excretion, and pharmacokinetics". The Journal of Pharmacology and Experimental Therapeutics. 306 (1): 73–83. doi:10.1124/jpet.103.049882. PMID 12660312. S2CID 6147566.
  142. ↑ Morales-Garcia JA, Calleja-Conde J, Lopez-Moreno JA, Alonso-Gil S, Sanz-SanCristobal M, Riba J, Perez-Castillo A (September 2020). "N,N-dimethyltryptamine compound found in the hallucinogenic tea ayahuasca, regulates adult neurogenesis in vitro and in vivo". Translational Psychiatry. 10 (1): 331. doi:10.1038/s41398-020-01011-0. PMC 7522265. PMID 32989216.
  143. 1 2 3 4 5 6 7 8 9 10 11 12 Keiser MJ, Setola V, Irwin JJ, Laggner C, Abbas AI, Hufeisen SJ, et al. (November 2009). "Predicting new molecular targets for known drugs". Nature. 462 (7270): 175–81. Bibcode:2009Natur.462..175K. doi:10.1038/nature08506. PMC 2784146. PMID 19881490.
  144. 1 2 Deliganis AV, Pierce PA, Peroutka SJ (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.
  145. 1 2 3 4 5 Pierce PA, Peroutka SJ (1989). "Hallucinogenic drug interactions with neurotransmitter receptor binding sites in human cortex". Psychopharmacology. 97 (1): 118–22. doi:10.1007/BF00443425. PMID 2540505. S2CID 32936434.
  146. 1 2 3 4 5 6 7 8 9 10 11 12 Ray TS (February 2010). "Psychedelics and the human receptorome". PLOS ONE. 5 (2): e9019. Bibcode:2010PLoSO...5.9019R. doi:10.1371/journal.pone.0009019. PMC 2814854. PMID 20126400.
  147. 1 2 3 4 5 Smith RL, Canton H, Barrett RJ, 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. S2CID 27591297.
  148. ↑ Rothman RB, Baumann MH (May 2009). "Serotonergic drugs and valvular heart disease". Expert Opinion on Drug Safety. 8 (3): 317–29. doi:10.1517/14740330902931524. PMC 2695569. PMID 19505264.
  149. ↑ Roth BL (January 2007). "Drugs and valvular heart disease". The New England Journal of Medicine. 356 (1): 6–9. doi:10.1056/NEJMp068265. PMID 17202450.
  150. ↑ Urban JD, Clarke WP, von Zastrow M, Nichols DE, Kobilka B, Weinstein H, et al. (January 2007). "Functional selectivity and classical concepts of quantitative pharmacology". The Journal of Pharmacology and Experimental Therapeutics. 320 (1): 1–13. doi:10.1124/jpet.106.104463. PMID 16803859. S2CID 447937.
  151. ↑ Burchett SA, Hicks TP (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. OCLC 231983957. PMID 16962229. S2CID 10272684. Archived from the original (PDF) on 1 February 2012.
  152. 1 2 3 Fontanilla D, Johannessen M, Hajipour AR, Cozzi NV, Jackson MB, Ruoho AE (February 2009). "The hallucinogen N,N-dimethyltryptamine (DMT) is an endogenous sigma-1 receptor regulator". Science. 323 (5916): 934–7. Bibcode:2009Sci...323..934F. doi:10.1126/science.1166127. PMC 2947205. PMID 19213917.
  153. 1 2 Cozzi NV, Gopalakrishnan A, Anderson LL, Feih JT, Shulgin AT, Daley PF, Ruoho AE (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. S2CID 15928043. Archived from the original (PDF) on 17 June 2010. Retrieved 20 November 2010.
  154. ↑ Glennon RA (1994). "Classical hallucinogens: an introductory overview" (PDF). In Lin GC, Glennon RA (eds.). Hallucinogens: An Update. 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.
  155. ↑ Fantegrossi WE, Murnane KS, Reissig CJ (January 2008). "The behavioral pharmacology of hallucinogens". Biochemical Pharmacology. 75 (1): 17–33. doi:10.1016/j.bcp.2007.07.018. PMC 2247373. PMID 17977517.
  156. 1 2 3 Nichols DE (February 2004). "Hallucinogens". Pharmacology & Therapeutics. 101 (2): 131–81. doi:10.1016/j.pharmthera.2003.11.002. PMID 14761703.
  157. ↑ Vollenweider FX, Vollenweider-Scherpenhuyzen MF, 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. S2CID 37706068.
  158. 1 2 Strassman RJ (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. S2CID 4047951.
  159. ↑ Glennon RA, Titeler M, McKenney JD (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.
  160. ↑ Roth BL, Choudhary MS, Khan N, Uluer AZ (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). The Journal of Pharmacology and Experimental Therapeutics. 280 (2): 576–83. PMID 9023266.
  161. ↑ Canal CE, Olaghere da Silva UB, Gresch PJ, Watt EE, Sanders-Bush E, Airey DC (April 2010). "The serotonin 2C receptor potently modulates the head-twitch response in mice induced by a phenethylamine hallucinogen". Psychopharmacology. 209 (2): 163–74. doi:10.1007/s00213-010-1784-0. PMC 2868321. PMID 20165943.
  162. 1 2 Su TP, Hayashi T, Vaupel DB (March 2009). "When the endogenous hallucinogenic trace amine N,N-dimethyltryptamine meets the sigma-1 receptor". Science Signaling. 2 (61): pe12. doi:10.1126/scisignal.261pe12. PMC 3155724. PMID 19278957.
  163. ↑ Morinan A, Collier JG (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. S2CID 43576890.
  164. ↑ 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. hdl:11858/00-001M-0000-0029-D137-5. PMID 11086995. S2CID 6364237.
  165. ↑ Rickli A, Moning OD, Hoener MC, Liechti ME (August 2016). "Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens" (PDF). European Neuropsychopharmacology. 26 (8): 1327–37. doi:10.1016/j.euroneuro.2016.05.001. PMID 27216487. S2CID 6685927.
  166. ↑ Black L. "New on the Black Market: Vape Pens Full of DMT". The Stranger.
This article is issued from Offline. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.