DMT (1) - Science & Psychedelia

I thought an article on DMT and dreaming would be interesting, since there is a great deal of theory on this topic, but little real empirical data or research. This is the first of a short series of DMT articles I am posting. Please follow any links in the text/click the 'DMT' label below the article, to see further articles or previous posts which may be of interest.

N,N-Dimethyltryptamine (DMT or N,N-DMT) is a naturally occurring psychedelic compound of the tryptamine group, found widely throughout the plant kingdom. DMT occurs in trace amounts in mammals, including humans, where it putatively functions as a trace amine neurotransmitter. It is derived originally from the essential amino acid, tryptophan and is ultimately produced by the enzyme INMT during normal metabolism. Structurally, DMT is analogous to the neurotransmitter serotonine (5-HT), the hormone melatonin and other psychadelic tryptamines, such as 5-MeO-DMT, bufotenin and psilocin (the active metabolite of psiolcybin). The significance of the widespread natural presence of DTM remains largely undetermined. 

Ingested, DMT acts as a psychedelic drug, and depending on dosage and method of administration, subjective effects range from short-live psychedelic states to powerfully immersive dream-like experiences which are often described as a total loss of connection from conventional reality and an encounter with alien realms. Indigenous Amazonian Amerindian cultures ingest DMT as the primary psychoactive in ‘avahuasca’ (combined with MAOI, an enzyme inhibitor which allows DMT to be orally active) – a shamanistic brew which is used for divinatory and healing purposes.

The following section of information was sourced (and partially edited by myself, with great difficulty and a lot of cross-referencing!) from the Wikipedia entry on DMT. I do not claim to understand the bio-chemistry/pharmacology (I have enough trouble teaching myself psychology and understanding neuroscience and lucid dream supplements, all of which are a lot simpler for me to learn than the material I have posted below). However, to provide a comprehensive article on what DMT is – or is thought to be – I felt it was important to include the ‘science bit’ for my readers who may have more expertise or knowledge in this area. If, like myself, the following section is a little too dense to mentally digest in one go, I recommend skipping down to the section ‘The psychedelic effects of DMT’ and reading from there onwards, where I cover DMT as a psychedelic/hallucinogenic drug and thereafter DMT and theories of dreaming, which shall appear as a second post. I chose to present the scientific material in a very similar, if slightly re-phrased, manner to the way in which it originally appeared on Wikipedia, as I am not competent enough to ensure the scientific information is correct if I were to change the content too much, and I am confident Wikipedia, which cites all referenced articles/sources, is much more reliable than myself in this respect. Thereafter, the remaining sections of this article are written from a variety of different resources I found during my research and some original observations from myself upon such material.

The scientific history of DMT

DMT was first synthesised by Canadian chemist, Richard Helmuth Fredrick Manske (1901 – 1977) in 1931, although its discovery as an organic product is generally credited to Brazilian chemist and microbiologist, Oswaldo Goncalves de Lima (1908 – 1989) in 1946, when he isolated an alkaloid (‘nigerina’ – i.e. nigerine) from the root bark of the jurema preta (the mimosa tenuflora). However, in a review of the evidence, Jonathan Ott demonstrated how  the empirical formula for nigerine – which notably contains an atom of oxygen – can only match a partial ‘impure’ or ‘contaminated’ form of DMT. In 1959, Gonzales de Lima provided American scientists with a sample of mimosa tenuflora and DMT was unequivocally identified as existing in this plant material. In 1955 DMT has been formally identified in the seeds and pods of the anadenanthera peregrina by a team of American chemists led by Evan Horning (1916 – 1993). Since 1955, DMT has been discovered in a range of different host organisms – in at least 50 different plant species belonging to 10 genotypes; and at least four animal species, including one gorgonian and three mammalian species. This form of DMT is known as ‘endogenous DMT’.

Another breakthrough in the scientific history of DMT is its discovery in plants frequently used by the Amazonian natives, which is added to the vine, banisteriopsis caapi to make avahuasca decoctions. In 1957, American chemists, Hochstein and Paradies identified DMT in an ‘aquseous extract’ of leaves of a plant named prestonia amazonicum and it was described as being commonly mixed with b. caapi. The lack of proper botanical identification of prestonia amazonicum in this study, led American entheo-botanist Richard Evans Schultes (1915 – 2001) and other scientists to raise serious doubts as to the claimed identity of the plant. Further, strengthened evidence was presented in 1965 by French pharmacologist, Jacques Poisson, who isolated DMT as a sole alkaloid from leaves provided and used by Aguaruna Indians which was identified as pertaining to the vine diplopterys cabrerana (also known as banisteriopsis rusbyana). The first identification of DMT in other commonly used plant additive, psychotria viridis, was published in 1970 by pharmacologist Ara der Marderosian, and a group of American scientists. Not only were they able to detect DMT in the leaves of the p. viridis obtained from Cashinahua Indians, but they were also the first scientists to identify it in a sample of ayahuasxa decoction, prepared by the same group of Indians. 

Dimethyltryptamine is an indole alkaloid derived from the shikimate pathway. Its biosynthesis is relatively simple and summarised in the diagramatic image attached to this post (below). In plants, the parent amino acid L-tryptophan is produced endogenously; whereas 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) catalyses 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). 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 and DMT 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 radio-labeling of SAM methyl group with carbon-14.

Published in Science (1961), Julius Axelrod found an N-methyltransferase enzyme capable of mediating biotransformation of tryptamine into DMT in a rabbit's lung. This discovery initiated a still ongoing scientific interest in endogenous DMT production in humans and other mammals. From then on, two major complementary lines of evidence have been investigated: localisation and further characterisation of the N-methyltransferase enzyme; and analytical studies looking for endogenously produced DMT in body fluids and tissues.

Before techniques of molecular biology were used to localise indolethylamine N-methyltransferase (INMT), characterisation and localisation went on a par - samples of the biological material where INMT is hypothesised to be active are subject to enzyme assay. Those enzyme assays are performed either with a radio-labeled methyl donor like (14C-CH3)SAM to which known amounts of unlabeled substrates like tryptamine are added, or with addition of a radio-labeled substrate like (14C)NMT to demonstrate in vivo formation. As qualitative determination of the radioactively tagged product of the enzymatic reaction is sufficient to characterise INMT existence and activity (or lack of), analytical methods used in INMT assays aren't 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. Also, robust evidence that INMT can catalyse transmethylation of tryptamine into NMT and DMT could be provided with reverse isotope dilution analysis coupled to mass spectrometry for rabbit and human 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 and negligible amounts of DMT in brain tissue. It is indeed simultaneously realised that the TLC methods used thus far in almost all published studies on INMT and DMT biosynthesis are incapable to resolve DMT from those tetrahydro-β-carbolines.

These findings are a blow for all previous claims of evidence of INMT activity and DMT biosynthesis in avian and mammalian brain, including in vivo, as they all relied upon use of the problematic TLC methods; their validity is doubted in replication studies that make use of improved TLC methods, and fail to evidence DMT-producing INMT activity in rat and human brain tissues. Published in 1978, the last study attempting to evidence in vivo INMT activity and DMT production in brain (rat) with TLC methods finds biotransformation of radio-labeled tryptamine into DMT to be real but "insignificant". Capability of the method used in this latter study to resolve DMT from tetrahydro-β-carbolines is questioned later. To localise INMT, a qualitative leap is accomplished with use of modern techniques of molecular biology, and of immune-histo-chemistry. In humans, a gene encoding INMT is determined to be located on chromosome 7. Northern blot analyses reveal INMT messenger RNA (mRNA) to be highly expressed in rabbit lung, and in human thyroid, adrenal gland, and lung.  Intermediate levels of expression are found in human heart, skeletal muscle, trachea, stomach, small intestine, pancreas, testis, prostate, placenta, lymph node, and spinal cord. Low to very low levels of expression are noted in rabbit brain, and human thymus, liver, spleen, kidney, colon, ovary, and bone marrow.  INMT mRNA expression is absent in human peripheral blood leukocytes, whole brain, and in tissue from seven specific brain regions (thalamus, subthalamic nucleus, caudate nucleus, hippocampus, amygdala, substantia nigra, and corpus callosum). Immunohistochemistry showed INMT to be present in large amounts in glandular epithelial cells of small and large intestines, and to be absent in neurons. The first claimed detection of mammalian endogenous DMT was published in June 1965 - German researchers Franzen and Gross report to have evidenced and quantified DMT, along with its structural analog bufotenin (5-OH-DMT), in human blood and urine. In an article published four months later, the method used in their study is strongly criticised, and credibility of their results challenged. In 2001, surveys, made in research articles, point that few of the analytical methods previously used to measure levels of endogenously formed DMT had enough sensitivity and selectivity to produce reliable results. Gas chromatography, preferably coupled to mass spectrometry (GC-MS), is considered a minimum requirement. A study published in 2005 implements the most sensitive and selective method ever used to measure endogenous DMT - liquid chromatography-tandem mass spectrometry with electrospray ionization (LC-ESI-MS/MS) allows to reach limits of detection (LODs) 12 to 200 fold lower (that is, better) than those attained by the best methods employed in the 1970s.

DMT peak levels concentrations (Cmax) measured in whole blood after intramuscular (IM) injection (0.7 mg/kg, n = 11) and in plasma following intravenous (IV) administration (0.4 mg/kg, n = 10) of fully psychedelic doses are in the range of ≈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. 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. 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, and 2 minutes in plasma after IV administration. 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, and 90 – 120 minutes, respectively. The pharmacokinetics for smoking DMT have not been studied or reported. DMT binds non-selectively with affinities < 0.6 μM to the following serotonin receptors: 5-HT1A, 5-HT1B, 5-HT1D, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT6, and 5-HT7. An agonist action has been determined at 5-HT1A, 5-HT2A and 5-HT2C. Its efficacies at other serotonin receptors remain to be determined. Of special interest will be the determination of its efficacy at human 5-HT2B receptor as two in vitro assays evidenced DMT high affinity for this receptor: 0.108 μM and 0.184 μM. This may be of importance because chronic or frequent uses of serotonergic drugs showing preferential high affinity and clear agonism at 5-HT2B receptor have been causally linked to valvular heart disease. It has also been shown to possess affinity for the dopamine D1, α1-adrenergic, α2-adrenergic, imidazoline-1, sigma-1 (σ1), and trace amine-associated receptors. Agonism was demonstrated at 1 μM at the rat trace amine-associated receptor 1 (TAAR1) and converging lines of evidence established activation of the σ1 receptor at concentrations of 50 – 100 μM. Its efficacies at the other receptor binding sites are unclear. It has also been shown in vitro to be a substrate for the cell-surface serotonin transporter (SERT) and the intracellular vesicular monoamine transporter 2 (VMAT2), inhibiting SERT-mediated serotonin uptake in human platelets at an average concentration of 4.00 ± 0.70 μM and VMAT2-mediated serotonin uptake in vesicles (of army worm Sf9 cells) expressing rat VMAT-2 at an average concentration of 93 ± 6.8 μM. As with other so-called ‘classical hallucinogens’, a large part of DMT psychedelic effects can be attributed to a specific activation of the 5-HT2A receptor. 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. This range of values coincides well with the range of concentrations measured in blood and plasma after administration of a fully psychedelic dose. As DMT has been shown to have slightly better efficacy (EC50) at human serotonin 2C receptor than at 2A receptor, 5-HT2C highly likely also is implicated in DMT overall effects. Other receptors, such as 5-HT_1A σ1 and TAAR1 may also play a role.

In 2009 it was hypothesised that DMT may be an endogenous ligand for the σ1 receptor. The concentration of DMT needed for σ1 activation in vitro (50 – 100 μM) is similar to the behaviourally active concentration measured in mouse brain of approximately 106 μM. This is minimally 4 orders of magnitude (104) higher than the average concentrations measured in rat brain tissue or human plasma under basal conditions, so σ1 receptors are likely to be activated only under conditions of high local DMT concentrations. If DMT is stored in synaptic vesicles, such concentrations might occur during vesicular release.

To illustrate, while the average concentration of serotonin in brain tissue is in the 1.5 - 4 μM range, the concentration of serotonin in synaptic vesicles was measured at 270 mM. Following vesicular release, the resulting concentration of serotonin in the synaptic cleft, to which serotonin receptors are exposed, is estimated to be about 300 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.

DMT occurs naturally in many species of plants often in conjunction with its close chemical relatives 5-MeO-DMT and bufotenin (5-OH-DMT). DMT-containing plants are commonly used in South American Shamanic practices. It is usually one of the main active constituents of the drink ayahuasca, however ayahuasca is sometimes brewed with plants which don't produce DMT. It occurs as the primary psychoactive alkaloid in several plants including mimosa tenuiflora, diplopterys cabrerana, and psychotria viridis. DMT is found as a minor alkaloid in snuff made from virola bark resin in which 5-MeO-DMT is the main active alkaloid.  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. Psilocin, an active chemical in many psychedelic mushrooms, is structurally similar to DMT.

Molecular structures of DMT & harmala alkaloids

DMT molecule

Pure DMT crystals

DMT extraction

The psychedelic effects of 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 Institute 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. DMT can produce powerful entheogenic experiences including intense visuals, euphoria and hallucinations (perceived extensions of reality). DMT is generally not active orally unless it is combined with a monoamine oxidase inhibitor (MAOI) such as a reversible inhibitor of monoamine oxidase A (RIMA), for example, harmaline. Without an MAOI, the body quickly metabolises orally administered DMT, and it therefore has no hallucinogenic effect unless the dose exceeds monoamine oxidase's metabolic capacity. Other means of ingestion such as smoking or injecting the drug can produce powerful hallucinations and entheogenic activity for a short time (usually less than half an hour), as the DMT reaches the brain before it can be metabolised by the body's natural monoamine oxidase. Taking a MAOI prior to smoking or injecting DMT prolongs and potentiates the effects. A standard dose for vaporised DMT is between 15 – 60 mg. This is generally inhaled in a few successive breaths. The effects last for a short period of time, usually 5 - 15 minutes, depending on the dose. The onset after inhalation is very fast (less than 45 seconds) and peak effects are reached within a minute. In the 1960s, some reportedly referred to DMT as ‘the businessman's trip’ because of the relatively short duration (and rapid onset) of action when smoked. The most common way to administer DMT among people who use it is to vaporise it. The inhalation of DMT is most effectively achieved by vaporising it through the use of a glass pipe. Combining DMT with plant matter or depositing it upon a substrate of ash also facilitates use of an ordinary smoking pipe or a vaporiser. The vapour is sometimes described as harsh, and some users even compare its flavour and aroma to that of burning plastic or mothballs. Insufflating DMT (commonly as a freebase or fumarate) requires a higher dose than inhalation. The duration is markedly increased, and some users report diminished euphoria but an intensified otherworldly experience. A dose of approximately 70 - 120 mg of insufflated DMT will induce medium to strong effects. If successful in containing this pain inducing insufflation, the trip should last anywhere from 20 - 50 minutes, with undefinable peak(s). Injected DMT produces an experience that is similar to inhalation in duration, intensity, and characteristics.

In the 1950s, the endogenous production of psychoactive agents was considered to be a potential explanation for the hallucinatory symptoms of some psychiatric diseases as the transmethylation hypothesis, though this hypothesis does not account for the natural presence of endogenous DMT in otherwise normal humans, rats and other laboratory animals. Writers on DMT include Terence McKenna, Jeremy Narby and Graham Hancock. In his writings and speeches, McKenna recounts encounters with entities he sometimes describes as "Self-Transforming Machine Elves" among other phrases. McKenna believed DMT to be a tool that could be used to enhance communication and allow for communication with other-worldly entities. Other users report visitation from external intelligences attempting to impart information.

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. The Australian Federal Government is considering changes to the Australian Criminal Code that would classify any plants containing any amount of DMT as "controlled plants". As of February 2012, the Therapeutic Goods Administration and Federal Authority made a motion to not reschedule DMT or DMT containing substances as they may still hold potential entheogenic value to native and/or religious peoples. The final decision was handed down 1 May 2012. DMT is classified in Canada as a Schedule III drug. DMT, along with most of its plant sources, is classified in France as a stupéfiant (narcotic). DMT is classified in the United Kingdom and New Zealand as a Class A drug under the Misuse of Drugs Acts 1973 and 1975, respectively. 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 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 Religious Freedom Restoration Act 1993. 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, presided over by U.S. District Judge Owen M Panner, was ruled in favour 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. Panner issued a permanent injunction barring the government from prohibiting or penalising 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.

In South America there are a number of indigenous traditions and more recent religious movements based on the use of ayahuasca, usually in an animistic context that may be mixed with Christian imagery. There are three main groups using DMT-MAOI based sacraments in South America:

1. The Amazon Basin's indigenous population. There are many indigenous cultures in South America, mostly in the Upper Amazon Basin whose traditional religious practices include the use of ayahuasca. These are the oldest cultures in the whole of South America that continue to use ayahuasca or analogue brews, such as the ones made from Jurema in the Pernambuco, near Recife or Iquitos in Peru. 
2. Santo Daime ("Holy Give Unto Me") and Barquinha ("Little Boat") - asyncretic religion from Brazil. The former was founded by Raimundo Irineu Serra in the early 1930s, as an esoteric Christian religion with shamanic tendencies. The Barquinha was derived from this one. The Santo Daime also includes children in their Entheogenic rituals; studies done by the Brazilian government concluded that there were no physical or mental damage caused by this practice, so it is allowed.
3. União do Vegetal ("Union of the Plants" or UDV). Another Christian ayahuasca religion from Brazil, a single unified organization with a democratic structure.

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. DMT is naturally occurring in small amounts in rat brain, human cerebrospinal fluid, and other tissues of humans and other mammals.  It may play a role in mediating the visual effects of natural dreaming, and also near-death experiences, religious visions and other states. A biochemical mechanism for this was proposed by the medical researcher 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. A new hypothesis proposed is that in addition to being involved in altered states of consciousness, endogenous DMT may be involved in the creation of normal waking states of consciousness. It is proposed that DMT and other endogenous hallucinogens mediate their neurological abilities by acting as neurotransmitters at a sub-class of the trace amine receptors; a group of receptors found in the CNS where DMT and other hallucinogens have been shown to have activity. Wallach further proposes that in this way waking consciousness can be thought of as a controlled psychedelic experience. It is when the control of these systems becomes loosened and their behaviour no longer correlates with the external world that the altered states arise. 

During his talk Psychoactive Drugs Through-out Human History at a 1983 University of California at Santa Barbara conference, Andrew Weil mentioned: "Dimethyltryptamine...is almost certainly made by the pineal gland in the brain." Meanwhile, at U.C. San Diego, Strassman had begun to wonder whether or not the pineal might produce psychedelic compounds. That same year, in his booklet Eros and the Pineal: The Layman's Guide to Cerebral Solitaire, Albert Most claimed that: "A pair of naturally occurring pineal enzymes...is capable of converting serotonin into a number of potent hallucinogens." Most stated that the pineal could transform serotonin into 5-methoxy-N-methyltryptamine, and then make that into 5-methyoxy-N,N-dimethyltrptamine. Alas, no references were provided to support Most's description of pineal catabolism. Nevertheless, it seems likely that this general line of thinking - that some psychoactive tryptamine is created in the pineal - was developed in the early 1980s.

In a study conducted from 1990 - 1995, the University of New Mexico psychiatrist  Dr Rick Strassman found that some volunteers injected with high doses of DMT had 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.  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." DMT is broken down by the digestive enzyme monoamine oxidase through a process called deamination, and is therefore inactive if taken orally unless combined with a monoamine oxidase inhibitor (MAOI). The traditional South American ‘ayahuasca’, or ‘yage’, is a beverage 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. The Ayahuasca vine contains harmala alkaloids, highly active reversible inihibitors of monoamine oxidase A (RIMAs), rendering the DMT orally active by protecting it from deamination. A variety of different recipes are used to make the brew depending on the purpose of the ayahuasca session, 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 root-bark of this small tree contains a high concentration of N,N-DMT. Taken orally with an appropriate MAOI, DMT produces a long lasting (over 3 hour), slow, deep metaphysical experience similar to that of psilocybin mushrooms, but more intense. MAOIs should be used with extreme caution as they can have lethal complications with some prescription drugs such as SSRI antidepressants, some over-the-counter drugs and many common foods. 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. 5-MeO-DMT, a psychedelic drug structurally similar to N,N-DMT, is sometimes referred to as DMT through abbreviation. As a white, crystalline solid, it is also similar in appearance to DMT. However, it is considerably more potent (5-MeO-DMT typical smoked dose: 5 – 20 mg), and care should be taken to clearly differentiate between the two drugs to avoid accidental overdose. DMT may be quantitated in blood, plasma or urine using chromatographic techniques as a diagnostic tool in clinical poisoning situations or to aid in the medicolegal investigation of suspicious deaths. Blood or plasma DMT levels in recreational users of the drug are generally in the 10–30 μg/L range during the first several hours post-ingestion. Less than 0.1% of an oral dose is eliminated unchanged in the 24 hour urine of humans. Similar to other psychedelic drugs, there are relatively few physical side effects associated with DMT acute exposure. Second-hand accounts also exist of serious health complications from 5-MeO-DMT use which may be aggravated by interaction with MAOIs. When inhaled, its vapour has been described as "very harsh." According to a Strassman, Dose-response study of N,N-dimethyltryptamine in humans (1994), 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. Psychologically, the DMT experience can be overly-intense, potentially causing overwhelming fear and difficulty integrating experiences if one is not mentally prepared. Furthermore, due to the intense nature of the experience, DMT is generally considered to have no addiction potential.  Just as with all psychedelics, there is a chance for an onset of paranoia, or a 'bad trip'. This risk is more prevalent with DMT, as DMT is more intense than normal psychedelics. Close attention should be paid to dose, set and setting. Also one should note that despite the lack of physical side effects, the intensity of the DMT experience could trigger latent mental illnesses in those who may have a genetic predisposition to such diseases.

Strassman, while conducting his DMT research during the 1990s at the University of New Mexico, also advanced the controversial hypothesis that a massive release of DMT from the pineal gland (soma pinoline – see my next post on this topic) prior to death or near death was the cause of the near death experience (NDE) phenomenon. Several of his test subjects reported NDE-like 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, where the subjects were 'carried,' 'probed,' 'tested,' 'manipulated,' 'dismembered,' 'taught,' 'loved,' and even '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 (see evidence in mammals), 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. Currently there is no published reliable scientific evidence supporting this hypothesis and as such, it is merely a hypothesis. Strassman refers to DMT as the ‘spirit molecular’ and argues that it may be released in massive amounts, not just prior to death, but also at birth and during dreaming and hallucinations. However, in a study of “about 10” human brains from newly-dead corpses, Strassman found no traces of DMT in the pineal glands. This finding does not invalidate his theory, as it is known that DMT metabolises very quickly, and the brains were not fresh frozen at the time of death which may explain why no trace was present upon analysis. Empirical data from fresh-frozen human brains may shed further light on the theory of possible DMT production in the pineal gland and whether large amounts of it are released into the brain at death.

Strassman published a popular book on his findings, DMT: The Spirit Molecule, in 2001, which I discuss in the next post on this topic, which you can access by clicking on the 'DMT' label below this post. Strassman plans to continue his DMT research at the newly-founded Cottonwood Research Foundation in New Mexico. His vice president, Dr Steven Barker at Louisiana State University, is already developing a new ultra-sensitive method of measuring naturally occurring DMT in the body, which will hopefully enable scientists to empirically test Strassman’s controversial theory of pineal DMT (discussed in next post). They hope to be able to compare normal levels with those found in altered states under clinical conditions. Ultimately, Strassman and his team intend to develop a new model of consciousness studies in the Western world. They hope to explore the varieties of human consciousness and their genetic, biochemical and physiological bases - finding the best way to apply these states to healing, creativity and greater wisdom.

Please click on the label marked 'DMT' for further posts on this topic.