''N'',''N''-Dimethyltryptamine (DMT or ''N'',''N''-DMT, SPL026) is a
substituted tryptamine that occurs in many plants and animals, including human beings, and which is both a
derivative
In mathematics, the derivative of a function of a real variable measures the sensitivity to change of the function value (output value) with respect to a change in its argument (input value). Derivatives are a fundamental tool of calculus. ...
and a
structural analog
A structural analog (analogue in modern traditional English; Commonwealth English), also known as a chemical analog or simply an analog, is a compound having a structure similar to that of another compound, but differing from it in respect to a c ...
of
tryptamine
Tryptamine is an indolamine metabolite of the essential amino acid, tryptophan. The chemical structure is defined by an indole ─ a fused benzene and pyrrole ring, and a 2-aminoethyl group at the second carbon (third aromatic atom, with the f ...
.
It is used as a
psychedelic drug and prepared by various cultures for
ritual
A ritual is a sequence of activities involving gestures, words, actions, or objects, performed according to a set sequence. Rituals may be prescribed by the traditions of a community, including a religious community. Rituals are characterized ...
purposes as an
entheogen
Entheogens are psychoactive substances that induce alterations in perception, mood, consciousness, cognition, or behavior for the purposes of engendering spiritual development or otherwiseRätsch, Christian, ''The Encyclopedia of Psychoac ...
.
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
Lysergic acid diethylamide (LSD), also known colloquially as acid, is a potent psychedelic drug. Effects typically include intensified thoughts, emotions, and sensory perception. At sufficiently high dosages LSD manifests primarily mental, vi ...
or
psilocybin mushroom
Psilocybin mushrooms, commonly known as magic mushrooms, are a polyphyletic informal group of fungi that contain psilocybin which turns into psilocin upon ingestion. Biological genera containing psilocybin mushrooms include ''Psilocybe'', '' ...
s. 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.
DMT can produce vivid "projections" of
mystical experiences involving euphoria and dynamic
pseudohallucination
A pseudohallucination (from grc, ψευδής (pseudḗs) "false, lying" + "hallucination") is an involuntary sensory experience vivid enough to be regarded as a hallucination, but which is recognised by the person experiencing it as being subject ...
s of geometric forms.
DMT is a
functional analog and
structural analog
A structural analog (analogue in modern traditional English; Commonwealth English), also known as a chemical analog or simply an analog, is a compound having a structure similar to that of another compound, but differing from it in respect to a c ...
of other psychedelic tryptamines such as
''O''-acetylpsilocin (4-AcO-DMT),
psilocybin
Psilocybin ( , ) is a naturally occurring psychedelic prodrug compound produced by more than 200 species of fungi. The most potent are members of the genus ''Psilocybe'', such as '' P. azurescens'', '' P. semilanceata'', and '' P.&nbs ...
(4-PO-DMT),
psilocin
Psilocin (also known as 4-HO-DMT, 4-hydroxy DMT, psilocine, psilocyn, or psilotsin) is a substituted tryptamine alkaloid and a serotonergic psychedelic substance. It is present in most psychedelic mushrooms together with its phosphorylated cou ...
(4-HO-DMT),
''O''-methylbufotenin (5-MeO-DMT), and
bufotenin
Bufotenin (5-HO-DMT, bufotenine) is a tryptamine derivative - more specifically, a DMT derivative - related to the neurotransmitter serotonin. It is an alkaloid found in some species of toads (especially the skin), mushrooms and plants.
...
(5-HO-DMT). Parts of the structure of DMT occur 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
5-MeO-DMT (5-methoxy-''N'',''N''-dimethyltryptamine) or O-methyl-bufotenin is a psychedelic of the tryptamine class. It is found in a wide variety of plant species, and also is secreted by the glands of at least one toad species, the Colorado R ...
) and
bufotenin
Bufotenin (5-HO-DMT, bufotenine) is a tryptamine derivative - more specifically, a DMT derivative - related to the neurotransmitter serotonin. It is an alkaloid found in some species of toads (especially the skin), mushrooms and plants.
...
(5-OH-DMT).
DMT-containing plants are commonly used in
indigenous Amazonian shamanic practices. It is usually one of the main active constituents of the drink
ayahuasca
AyahuascaPronounced as in the UK and in the US. Also occasionally known in English as ''ayaguasca'' ( Spanish-derived), ''aioasca'' (Brazilian Portuguese-derived), or as ''yagé'', pronounced or . Etymologically, all forms but ''yagé'' desce ...
;
however, ayahuasca is sometimes brewed with plants that do not produce DMT. It occurs as the primary psychoactive
alkaloid
Alkaloids are a class of basic, naturally occurring organic compounds that contain at least one nitrogen atom. This group also includes some related compounds with neutral and even weakly acidic properties. Some synthetic compounds of similar ...
in several plants including ''
Mimosa tenuiflora
''Mimosa tenuiflora'', syn. ''Mimosa hostilis'', also known as jurema preta, calumbi (Brazil), tepezcohuite (México), carbonal, cabrera, jurema, black jurema, and binho de jurema, is a perennial tree or shrub native to the northeastern region of ...
'', ''
Diplopterys cabrerana'', and ''
Psychotria viridis
''Psychotria viridis'', also known as ''chacruna'', ''chacrona'', or ''chaqruy'' in the Quechua languages, is a perennial, shrubby flowering plant in the coffee family Rubiaceae. It is a close relative of '' Psychotria carthagenensis'' (a.k.a. ...
''. DMT is found as a minor alkaloid in snuff made from
Virola
''Virola'' is a genus of medium-sized trees native to the South American rainforest and closely related to other Myristicaceae, such as nutmeg. Species are known commonly as ''epená'', ''patricá'', or ''cumala''. They have glossy, dark green le ...
bark resin in which
5-MeO-DMT
5-MeO-DMT (5-methoxy-''N'',''N''-dimethyltryptamine) or O-methyl-bufotenin is a psychedelic of the tryptamine class. It is found in a wide variety of plant species, and also is secreted by the glands of at least one toad species, the Colorado R ...
is the main active alkaloid.
DMT is also found as a minor alkaloid in bark, pods, and beans of ''
Anadenanthera peregrina'' and ''
Anadenanthera colubrina
''Anadenanthera colubrina'' (also known as vilca, huilco, huilca, wilco, willka, curupay, curupau, cebil, or angico) is a South American tree closely related to yopo, or ''Anadenanthera peregrina''. It grows to tall and the trunk is very thorn ...
'' used to make
Yopo
''Anadenanthera peregrina'', also known as yopo, jopo, cohoba, parica or calcium tree, is a perennial tree of the genus ''Anadenanthera'' native to the Caribbean and South America. It grows up to tall, and has a horny bark. Its flowers grow ...
and
Vilca snuff, in which bufotenin is the main active alkaloid.
Psilocin
Psilocin (also known as 4-HO-DMT, 4-hydroxy DMT, psilocine, psilocyn, or psilotsin) is a substituted tryptamine alkaloid and a serotonergic psychedelic substance. It is present in most psychedelic mushrooms together with its phosphorylated cou ...
and its precursor
psilocybin
Psilocybin ( , ) is a naturally occurring psychedelic prodrug compound produced by more than 200 species of fungi. The most potent are members of the genus ''Psilocybe'', such as '' P. azurescens'', '' P. semilanceata'', and '' P.&nbs ...
, an active chemical in many
psilocybin mushroom
Psilocybin mushrooms, commonly known as magic mushrooms, are a polyphyletic informal group of fungi that contain psilocybin which turns into psilocin upon ingestion. Biological genera containing psilocybin mushrooms include ''Psilocybe'', '' ...
s, 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
The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late ...
, had turned his attention to DMT after his order for
LSD
Lysergic acid diethylamide (LSD), also known colloquially as acid, is a potent psychedelic drug. Effects typically include intensified thoughts, emotions, and sensory perception. At sufficiently high dosages LSD manifests primarily mental, vi ...
from the Swiss company
Sandoz Laboratories
Novartis AG is a Swiss-American multinational pharmaceutical corporation based in Basel, Switzerland and
Cambridge, Massachusetts, United States (global research).name="novartis.com">https://www.novartis.com/research-development/research-loca ...
was rejected on the grounds that the powerful psychotropic could be dangerous in the hands of a communist country.
[ ()]
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
Harmaline is a fluorescent indole alkaloid from the group of harmala alkaloids and beta-carbolines. It is the partly hydrogenated form of harmine.
Occurrence in nature
Various plants contain harmaline including ''Peganum harmala'' (Syrian rue) ...
.
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 consumption 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.
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
Brain ischemia is a condition in which there is insufficient bloodflow to the brain to meet metabolic demand. This leads to poor oxygen supply or cerebral hypoxia and thus leads to the death of brain tissue or cerebral infarction/ischemic stroke. ...
.
DMT is studied as a potential treatment for
Parkinson’s disease
Parkinson's disease (PD), or simply Parkinson's, is a chronic condition, long-term neurodegeneration, degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disea ...
in a
Phase 1/2 clinical trial.
SPL026 (DMT fumarate) is currently undergoing
phase II clinical trials
The phases of clinical research are the stages in which scientists conduct experiments with a health intervention to obtain sufficient evidence for a process considered effective as a medical treatment. For drug development, the clinical phases ...
investigating its use alongside supportive psychotherapy as a potential treatment
Major Depressive Disorder
Major depressive disorder (MDD), also known as clinical depression, is a mental disorder characterized by at least two weeks of pervasive low mood, low self-esteem, and loss of interest or pleasure in normally enjoyable activities. Intro ...
. Additionally, a safety study is underway to investigate the effects of combining SSRIs with SPL026.
Neuropharmocology
Recently, researchers discovered that N,N-Dimethyltryptamine (DMT or N,N-DMT) is a potent
psychoplastogen, a compound capable of promoting rapid and sustained
neuroplasticity
Neuroplasticity, also known as neural plasticity, or brain plasticity, is the ability of neural networks in the brain to change through growth and reorganization. It is when the brain is rewired to function in some way that differs from how it p ...
that may have wide-ranging therapeutic benefit.
Quantities of dimethyltryptamine and
''O''-methylbufotenin were found present in the cerebrospinal fluid of humans in a psychiatric study.
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.
Examples include perceiving
hyperbolic geometry
In mathematics, hyperbolic geometry (also called Lobachevskian geometry or Bolyai–Lobachevskian geometry) is a non-Euclidean geometry. The parallel postulate of Euclidean geometry is replaced with:
:For any given line ''R'' and point ''P ...
or seeing
Escher-like
impossible object
An impossible object (also known as an impossible figure or an undecidable figure) is a type of optical illusion that consists of a two- dimensional figure which is instantly and naturally understood as representing a projection of a three-d ...
s.
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
Rick Strassman is an American clinical associate professor of psychiatry at the University of New Mexico School of Medicine. He has held a fellowship in clinical psychopharmacology research at the University of California San Diego and was Profess ...
and his colleagues conducted a five-year-long DMT study at the
University of New Mexico
The University of New Mexico (UNM; es, Universidad de Nuevo México) is a public research university in Albuquerque, New Mexico. Founded in 1889, it is the state's flagship academic institution and the largest by enrollment, with over 25,400 ...
in the 1990s.
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 some aesthetic and emotional responses, but not hallucinogenic experiences (e.g., 0.05 mg/kg had mild mood elevating and calming properties).
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.
These dose-dependent effects match well with anonymously posted "trip reports" online, where users report "breakthroughs" above certain doses.
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.
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".
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.
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. 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.
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
Terence Kemp McKenna (November 16, 1946 – April 3, 2000) was an American ethnobotanist and mystic who advocated the responsible use of naturally occurring psychedelic plants. He spoke and wrote about a variety of subjects, including ...
for the entities he encountered in DMT "hyperspace", also using terms like ''fractal elves'', or ''self-transforming machine elves''. 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.
Cliff Pickover
Clifford Alan Pickover (born August 15, 1957) is an American author, editor, and columnist in the fields of science, mathematics, science fiction, innovation, and creativity. For many years, he was employed at the IBM Thomas J. Watson Resea ...
has also written about the "machine elf" experience, in the book ''Sex, Drugs, Einstein, & Elves''.
Strassman noted similarities between self-reports of his DMT study participants' encounters with these "entities", and mythological descriptions of figures such as
Ḥayyot haq-Qodesh in ancient religions, including both angels and demons.
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
In biology, an organism () is any living system that functions as an individual entity. All organisms are composed of cells (cell theory). Organisms are classified by taxonomy into groups such as multicellular animals, plants, and fungi; ...
and
Ophanim
The ophanim (Hebrew: ''ʿōp̄annīm'', "wheels"; singular: ''ʿōp̄ān'', “Ofan”), alternatively spelled ''auphanim'' or ''ofanim'', and also called ''galgalim'' (Hebrew: ''galgallīm'', "spheres", "wheels", "whirlwinds"; singular: ''gal ...
of the Hebrew Bible, noting they may stem from a common
neuropsychopharmacological experience.
Strassman argues that the more positive of the "external entities" encountered in DMT experiences should be understood as analogous to certain forms of angels:
Strassman's experimental participants also note that some other entities can subjectively resemble creatures more like insects and aliens. 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."
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.
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
A gnome is a mythological creature and diminutive spirit in Renaissance magic and alchemy, first introduced by Paracelsus in the 16th century and later adopted by more recent authors including those of modern fantasy literature. Its character ...
, elves,
imps IMPS or Imps may refer to:
* ''Imps*'', a comedy film released in 2009
* OMA Instant Messaging and Presence Service
* Infinite Monkey Protocol Suite, an April Fools' Day RFC
* The Oxford Imps, an improvisational comedy troupe
* Insensitive muni ...
, etc.).
Strassman and others have speculated that this form of hallucination may be the cause of
alien abduction
Alien abduction (also called abduction phenomenon, alien abduction syndrome, or UFO abduction) refers to the phenomenon of people reporting their experience of being kidnapped by extraterrestrial beings and subjected to physical and psychologica ...
and extraterrestrial encounter experiences, which may occur through
endogenously-occurring DMT.
Likening them to descriptions of rattling and chattering auditory phenomena described in encounters with the
Hayyoth
The living creatures, living beings, or ''hayyot'' (Hebrew חַיּוֹת ''ḥayyōṯ'') are a class of heavenly beings in Jewish mythology. They are described in the prophet Ezekiel's vision of the heavenly chariot in the first and tenth ch ...
in the
Book of Ezekiel
The Book of Ezekiel is the third of the Latter Prophets in the Tanakh and one of the major prophetic books, following Isaiah and Jeremiah. According to the book itself, it records six visions of the prophet Ezekiel, exiled in Babylon, during ...
, 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".
Near-death experience
A 2018 study found significant relationships between a DMT experience and a
near-death experience
A near-death experience (NDE) is a profound personal experience associated with death or impending death which researchers claim share similar characteristics. When positive, such experiences may encompass a variety of sensations including detac ...
. A 2019 large-scale study found that
ketamine
Ketamine is a dissociative anesthetic used medically for induction and maintenance of anesthesia. It is also used as a recreational drug. It is one of the safest anesthetics, as, in contrast with opiates, ether, and propofol, it suppresses ...
, ''
Salvia divinorum'', and DMT (and other classical psychedelic substances) are linked to
near-death experience
A near-death experience (NDE) is a profound personal experience associated with death or impending death which researchers claim share similar characteristics. When positive, such experiences may encompass a variety of sensations including detac ...
s.
Physiological response
According to a dose-response study in human subjects, dimethyltryptamine administered
intravenously
Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrie ...
slightly elevated blood pressure, heart rate, pupil diameter, and rectal temperature, in addition to elevating blood concentrations of beta-
endorphin
Endorphins (contracted from endogenous morphine) are chemical signals in the brain that block the perception of pain and increase feelings of wellbeing. They are produced and stored in an area of the brain known as the pituitary gland.
Hist ...
,
corticotropin
Adrenocorticotropic hormone (ACTH; also adrenocorticotropin, corticotropin) is a polypeptide tropic hormone produced by and secreted by the anterior pituitary gland. It is also used as a medication and diagnostic agent. ACTH is an important ...
,
cortisol, and
prolactin
Prolactin (PRL), also known as lactotropin, is a protein best known for its role in enabling mammals to produce milk. It is influential in over 300 separate processes in various vertebrates, including humans. Prolactin is secreted from the pit ...
;
growth hormone
Growth hormone (GH) or somatotropin, also known as human growth hormone (hGH or HGH) in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. It is thus important in h ...
blood levels rise equally in response to all doses of DMT, and
melatonin levels were unaffected."
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.
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.
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.
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.
In 2011, Nicholas V. Cozzi, of the
University of Wisconsin School of Medicine and Public Health
A university () is an institution of higher (or tertiary) education and research which awards academic degrees in several academic disciplines. Universities typically offer both undergraduate and postgraduate programs. In the United States, the ...
, 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.
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.
Routes of administration
Inhalation
![Vapor Genie DMT Vaporization Pipe](https://upload.wikimedia.org/wikipedia/commons/5/50/Vapor_Genie_DMT_Vaporization_Pipe.png)
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. 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 "businessman's trip" in the US because of the relatively short duration (and rapid onset) of action when inhaled. DMT can be inhaled using a
bong
A bong (also known as a water pipe) is a filtration device generally used for smoking cannabis, tobacco, or other herbal substances. In the bong shown in the photo, the gas flows from the lower port on the left to the upper port on the right.
...
, typically when sandwiched between layers of plant matter, using a specially designed pipe, or by using an
e-cigarette
An electronic cigarette is an electronic device that simulates tobacco smoking. It consists of an atomizer, a power source such as a battery, and a container such as a cartridge or tank. Instead of smoke, the user inhales vapor. As such ...
once it has been dissolved in propylene glycol and/or vegetable glycerin. 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
The University of New Mexico (UNM; es, Universidad de Nuevo México) is a public research university in Albuquerque, New Mexico. Founded in 1889, it is the state's flagship academic institution and the largest by enrollment, with over 25,400 ...
psychiatrist
Rick Strassman
Rick Strassman is an American clinical associate professor of psychiatry at the University of New Mexico School of Medicine. He has held a fellowship in clinical psychopharmacology research at the University of California San Diego and was Profess ...
found that some volunteers injected with high doses of DMT reported experiences with perceived
alien
Alien primarily refers to:
* Alien (law), a person in a country who is not a national of that country
** Enemy alien, the above in times of war
* Extraterrestrial life, life which does not originate from Earth
** Specifically, intelligent extrater ...
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.
Oral ingestion
![Aya-preparation](https://upload.wikimedia.org/wikipedia/commons/e/e7/Aya-preparation.jpg)
DMT is broken down by the enzyme
monoamine oxidase through a process called
deamination
Deamination is the removal of an amino group from a molecule. Enzymes that catalyse this reaction are called deaminases.
In the human body, deamination takes place primarily in the liver, however it can also occur in the kidney. In situations of ...
, and is quickly inactivated orally unless combined with a
monoamine oxidase inhibitor (MAOI).
The traditional South American beverage
ayahuasca
AyahuascaPronounced as in the UK and in the US. Also occasionally known in English as ''ayaguasca'' ( Spanish-derived), ''aioasca'' (Brazilian Portuguese-derived), or as ''yagé'', pronounced or . Etymologically, all forms but ''yagé'' desce ...
, 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 viridis'', also known as ''chacruna'', ''chacrona'', or ''chaqruy'' in the Quechua languages, is a perennial, shrubby flowering plant in the coffee family Rubiaceae. It is a close relative of '' Psychotria carthagenensis'' (a.k.a. ...
'', ''
Psychotria carthagenensis'', or ''
Diplopterys cabrerana''.
The Ayahuasca vine contains
harmala alkaloids
Several alkaloids that function as monoamine oxidase inhibitors (MAOIs) are found in the seeds of ''Peganum harmala'' (also known as ''Harmal'' or ''Syrian Rue''), as well as tobacco leaves including harmine, harmaline, and harmalol, which are m ...
,
highly active reversible inihibitors of monoamine oxidase A (
RIMA
Rima, also known as Rima the Jungle Girl, is the fictional heroine of W. H. Hudson's 1904 novel '' Green Mansions: A Romance of the Tropical Forest''. In it, Rima, a primitive girl of the shrinking rain forest of South America, meets Abel, a pol ...
s),
rendering the DMT orally active by protecting it from
deamination
Deamination is the removal of an amino group from a molecule. Enzymes that catalyse this reaction are called deaminases.
In the human body, deamination takes place primarily in the liver, however it can also occur in the kidney. In situations of ...
.
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'', or reed canary grass, is a tall, perennial bunchgrass that commonly forms extensive single-species stands along the margins of lakes and streams and in wet open areas, with a wide distribution in Europe, Asia, northern ...
(''
Phalaris arundinacea
''Phalaris arundinacea'', or reed canary grass, is a tall, Perennial plant, perennial bunchgrass that commonly forms extensive single-species stands along the margins of lakes and streams and in wet open areas, with a wide distribution in Europe ...
'') and
Harding grass
''Phalaris aquatica'', known by the common names bulbous canary-grass and Harding grass, is a species of grass in the genus ''Phalaris'' of the family Poaceae.
Description
It is an erect, waist-high, stout perennial bunch grass, with grayish to ...
(''
Phalaris aquatica
''Phalaris aquatica'', known by the common names bulbous canary-grass and Harding grass, is a species of grass in the genus ''Phalaris'' of the family Poaceae.
Description
It is an erect, waist-high, stout perennial bunch grass, with grayish to ...
''). These invasive grasses contain low levels of DMT and other alkaloids but also contain
gramine
Gramine (also called donaxine) is a naturally occurring indole alkaloid present in several plant species. Gramine may play a defensive role in these plants, since it is toxic to many organisms.
Occurrence
Gramine has been found in the giant reed, ...
, which is toxic and difficult to separate. In addition,
Jurema (''
Mimosa tenuiflora
''Mimosa tenuiflora'', syn. ''Mimosa hostilis'', also known as jurema preta, calumbi (Brazil), tepezcohuite (México), carbonal, cabrera, jurema, black jurema, and binho de jurema, is a perennial tree or shrub native to the northeastern region of ...
'') 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
Rima, also known as Rima the Jungle Girl, is the fictional heroine of W. H. Hudson's 1904 novel '' Green Mansions: A Romance of the Tropical Forest''. In it, Rima, a primitive girl of the shrinking rain forest of South America, meets Abel, a pol ...
, DMT produces a long-lasting (over three hours), slow, deep metaphysical experience similar to that of
psilocybin mushrooms
Psilocybin mushrooms, commonly known as magic mushrooms, are a polyphyletic informal group of fungi that contain psilocybin which turns into psilocin upon ingestion. Biological genera containing psilocybin mushrooms include ''Psilocybe'', ''Pa ...
, but more intense.
RIMA
Rima, also known as Rima the Jungle Girl, is the fictional heroine of W. H. Hudson's 1904 novel '' Green Mansions: A Romance of the Tropical Forest''. In it, Rima, a primitive girl of the shrinking rain forest of South America, meets Abel, a pol ...
s 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.
The intensity of orally administered DMT depends on the type and dose of MAOI administered alongside it. When ingested with 120mg of
harmine
Harmine is a beta-carboline and a harmala alkaloid. It occurs in a number of different plants, most notably the Syrian rue and ''Banisteriopsis caapi''. Harmine reversibly inhibits monoamine oxidase A (MAO-A), an enzyme which breaks down monoamin ...
(a
RIMA
Rima, also known as Rima the Jungle Girl, is the fictional heroine of W. H. Hudson's 1904 novel '' Green Mansions: A Romance of the Tropical Forest''. In it, Rima, a primitive girl of the shrinking rain forest of South America, meets Abel, a pol ...
and member of the
harmala alkaloids
Several alkaloids that function as monoamine oxidase inhibitors (MAOIs) are found in the seeds of ''Peganum harmala'' (also known as ''Harmal'' or ''Syrian Rue''), as well as tobacco leaves including harmine, harmaline, and harmalol, which are m ...
), 20mg of DMT was reported to have psychoactive effects by author and
ethnobotanist
Ethnobotany is the study of a region's plants and their practical uses through the traditional knowledge of a local culture and people. An ethnobotanist thus strives to document the local customs involving the practical uses of local flora for m ...
Jonathan Ott
Jonathan Ott (born 1949 in Hartford, Connecticut) is an ethnobotanist, writer, translator, publisher, natural products chemist and botanical researcher in the area of entheogens and their cultural and historical uses, and helped coin the term "' ...
. Ott reported that to produce a visionary state, the threshold oral dose was 30mg DMT alongside 120mg
harmine
Harmine is a beta-carboline and a harmala alkaloid. It occurs in a number of different plants, most notably the Syrian rue and ''Banisteriopsis caapi''. Harmine reversibly inhibits monoamine oxidase A (MAO-A), an enzyme which breaks down monoamin ...
.
This is not necessarily indicative of a standard dose, as dose-dependent effects may vary due to individual variations in drug metabolism.
History
Naturally occurring substances (of both vegetable and animal origin) containing DMT have been used in South America since pre-Columbian times.
DMT was first synthesized in 1931 by chemist Richard Helmuth Fredrick Manske (born 1901 in Berlin, Germany – 1977).
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
''Mimosa tenuiflora'', syn. ''Mimosa hostilis'', also known as jurema preta, calumbi (Brazil), tepezcohuite (México), carbonal, cabrera, jurema, black jurema, and binho de jurema, is a perennial tree or shrub native to the northeastern region of ...
''.
However, in a careful review of the case
Jonathan Ott
Jonathan Ott (born 1949 in Hartford, Connecticut) is an ethnobotanist, writer, translator, publisher, natural products chemist and botanical researcher in the area of entheogens and their cultural and historical uses, and helped coin the term "' ...
shows that the
empirical formula
In chemistry, the empirical formula of a chemical compound is the simplest whole number ratio of atoms present in a compound. A simple example of this concept is that the empirical formula of sulfur monoxide, or SO, would simply be SO, as is the ...
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.
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.
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).
Since 1955, DMT has been
found in a host of organisms: in at least fifty plant species belonging to ten
families
Family (from la, familia) is a group of people related either by consanguinity (by recognized birth) or affinity (by marriage or other relationship). The purpose of the family is to maintain the well-being of its members and of society. Ideal ...
,
and in at least four animal species, including one
gorgonian 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. This is considered to be the converging link between the chemical structure DMT to its cultural consumption as a psychoactive and religious sacrament.
Another historical milestone is the discovery of DMT in plants frequently used by Amazonian natives as additive to the vine ''
Banisteriopsis caapi
''Banisteriopsis caapi'', also known as ayahuasca, caapi, soul vine, or yagé (yage), is a South American liana of the family Malpighiaceae. It is one half of ayahuasca, a decoction with a long history of its entheogenic (connecting to spirit) us ...
'' to make
ayahuasca
AyahuascaPronounced as in the UK and in the US. Also occasionally known in English as ''ayaguasca'' ( Spanish-derived), ''aioasca'' (Brazilian Portuguese-derived), or as ''yagé'', pronounced or . Etymologically, all forms but ''yagé'' desce ...
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''. The lack of a proper botanical identification of ''
Prestonia amazonica'' in this study led American
ethnobotanist
Ethnobotany is the study of a region's plants and their practical uses through the traditional knowledge of a local culture and people. An ethnobotanist thus strives to document the local customs involving the practical uses of local flora for m ...
Richard Evans Schultes (1915–2001) and other scientists to raise serious doubts about the claimed plant identity.
The mistake likely led the writer
William Burroughs
William Seward Burroughs II (; February 5, 1914 – August 2, 1997) was an American writer and visual artist, widely considered a primary figure of the Beat Generation and a major postmodern author who influenced popular cultur ...
to regard the DMT he experimented with in Tangier in 1961 as "Prestonia". 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'').
Published in 1970, the first identification of DMT in the plant ''
Psychotria viridis
''Psychotria viridis'', also known as ''chacruna'', ''chacrona'', or ''chaqruy'' in the Quechua languages, is a perennial, shrubby flowering plant in the coffee family Rubiaceae. It is a close relative of '' Psychotria carthagenensis'' (a.k.a. ...
'',
another common additive of ayahuasca, was made by a team of American researchers led by pharmacologist Ara der Marderosian. Not only did they detect DMT in leaves of ''P. viridis'' obtained from
Kaxinawá indigenous people
Indigenous peoples are culturally distinct ethnic groups whose members are directly descended from the earliest known inhabitants of a particular geographic region and, to some extent, maintain the language and culture of those original people ...
, but they also were the first to identify it in a sample of an ayahuasca decoction, prepared by the same indigenous people.
Legal status
International law
Internationally DMT is illegal, but ayahuasca and DMT brews and preparations are lawful. DMT is controlled by the Convention on Psychotropic Substances at the international level. The Convention makes it illegal to possess, buy, purchase, sell, to retail and to dispense without a licence.
By country and continent
In some countries Ayahuasca is a forbidden substance or a controlled substance or regulated substance while in other countries is not a controlled substance or is even all
allowed, permited, lawful and legal its consumption, sale, trade, shop, possession and production.
Asia
*
Israel
Israel (; he, יִשְׂרָאֵל, ; ar, إِسْرَائِيل, ), officially the State of Israel ( he, מְדִינַת יִשְׂרָאֵל, label=none, translit=Medīnat Yīsrāʾēl; ), is a country in Western Asia. It is situated ...
– DMT is an illegal substance; production, trade and possession are prosecuted as crimes.
*
India
India, officially the Republic of India (Hindi: ), is a country in South Asia. It is the seventh-largest country by area, the second-most populous country, and the most populous democracy in the world. Bounded by the Indian Ocean on the so ...
– DMT is completely illegal to produce, transport, trade in or possess with a minimum prison or jail punishment of ten years.
Europe
*
France
France (), officially the French Republic ( ), is a country primarily located in Western Europe. It also comprises of overseas regions and territories in the Americas and the Atlantic, Pacific and Indian Oceans. Its metropolitan area ...
– DMT, along with most of its plant sources, is classified as a ''stupéfiant'' (
narcotic).
*
Germany
Germany,, officially the Federal Republic of Germany, is a country in Central Europe. It is the second most populous country in Europe after Russia, and the most populous member state of the European Union. Germany is situated betwe ...
– DMT is prohibited as a class I drug.
*
Republic of Ireland
Ireland ( ga, Éire ), also known as the Republic of Ireland (), is a country in north-western Europe consisting of 26 of the 32 Counties of Ireland, counties of the island of Ireland. The capital and largest city is Dublin, on the eastern ...
– DMT is an illegal Schedule 1 drug under the
Misuse of Drugs Acts. An attempt in 2014 by a member of the
Santo Daime
Santo Daime () is a syncretic religion founded in the 1930s in the Brazilian Amazonian state of Acre by Raimundo Irineu Serra, known as Mestre Irineu. Santo Daime incorporates elements of several religious or spiritual traditions including Folk ...
church to gain a religious exemption to import the drug failed.
*
Latvia — DMT is prohibited as a Schedule I drug.
*
Netherlands
)
, anthem = ( en, "William of Nassau")
, image_map =
, map_caption =
, subdivision_type = Sovereign state
, subdivision_name = Kingdom of the Netherlands
, established_title = Before independence
, established_date = Spanish Netherl ...
– The drug is banned as it is classified as a List 1 Drug per the
Opium Law
The Opium Law (or ''Opiumwet'' in Dutch) is the section of the Dutch law which covers nearly all psychotropic drugs.
Origin and history
In 1912, the First International Opium Conference took place in The Hague, where agreements were made abou ...
. Production, trade and possession of DMT are prohibited.
*
Russia
Russia (, , ), or the Russian Federation, is a transcontinental country spanning Eastern Europe and Northern Asia. It is the largest country in the world, with its internationally recognised territory covering , and encompassing one-eig ...
– Classified as a Schedule I narcotic, including its derivatives (see
sumatriptan and
zolmitriptan).
*
Serbia
Serbia (, ; Serbian: , , ), officially the Republic of Serbia (Serbian: , , ), is a landlocked country in Southeastern and Central Europe, situated at the crossroads of the Pannonian Basin and the Balkans. It shares land borders with Hungar ...
– 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.
*
United Kingdom
The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom (UK) or Britain, is a country in Europe, off the north-western coast of the European mainland, continental mainland. It comprises England, Scotlan ...
– DMT is classified as a
Class A drug
These drugs are known in the UK as ''controlled drugs'', because this is the term by which the act itself refers to them. In more general terms, however, many of these drugs are also controlled by the Medicines Act 1968, there are many other dru ...
.
*
Belgium
Belgium, ; french: Belgique ; german: Belgien officially the Kingdom of Belgium, is a country in Northwestern Europe. The country is bordered by the Netherlands to the north, Germany to the east, Luxembourg to the southeast, France to th ...
- DMT cannot be possessed, sold, purchased or imported. Usage is not specifically prohibited, but since usage implies possession one could be prosecuted that way.
North America
*
Canada
Canada is a country in North America. Its ten provinces and three territories extend from the Atlantic Ocean to the Pacific Ocean and northward into the Arctic Ocean, covering over , making it the world's second-largest country by tot ...
– DMT is classified as a
Schedule III drug under the Controlled Drugs and Substances Act, but is legal for religious groups to use. As of 2022 DMT has been decriminalized in Vancouver, and there are now several outlets which openly sell this substance in numerous forms
There are also many websites purporting to sell DMT onlinewith seemingly no repercussion.
In 2017 the
Santo Daime
Santo Daime () is a syncretic religion founded in the 1930s in the Brazilian Amazonian state of Acre by Raimundo Irineu Serra, known as Mestre Irineu. Santo Daime incorporates elements of several religious or spiritual traditions including Folk ...
Church Céu do Montréal received religious exemption to use
Ayahuasca
AyahuascaPronounced as in the UK and in the US. Also occasionally known in English as ''ayaguasca'' ( Spanish-derived), ''aioasca'' (Brazilian Portuguese-derived), or as ''yagé'', pronounced or . Etymologically, all forms but ''yagé'' desce ...
as a sacrament in their rituals.
*
United States
The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territori ...
– DMT is classified in the United States as a
Schedule I drug under the
Controlled Substances Act of 1970
The Controlled Substances Act (CSA) is the statute establishing federal U.S. drug policy under which the manufacture, importation, possession, use, and distribution of certain substances is regulated. It was passed by the 91st United States ...
.
In December 2004, the
Supreme Court lifted a stay, thereby allowing the
Brazil
Brazil ( pt, Brasil; ), officially the Federative Republic of Brazil (Portuguese: ), is the largest country in both South America and Latin America. At and with over 217 million people, Brazil is the world's fifth-largest country by area ...
-based
União do Vegetal
The Beneficent Spiritist Center ''União do Vegetal'' ( pt, Centro Espírita Beneficente União do Vegetal, links=no ; or UDV) is a religious society founded on July 22, 1961 in Porto Velho ( Rondônia) by José Gabriel da Costa, known as Mest ...
(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
AyahuascaPronounced as in the UK and in the US. Also occasionally known in English as ''ayaguasca'' ( Spanish-derived), ''aioasca'' (Brazilian Portuguese-derived), or as ''yagé'', pronounced or . Etymologically, all forms but ''yagé'' desce ...
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
The Religious Freedom Restoration Act of 1993, Pub. L. No. 103-141, 107 Stat. 1488 (November 16, 1993), codified at through (also known as RFRA, pronounced "rifra"), is a 1993 United States federal law that "ensures that interests in religiou ...
.
In September 2008, the three
Santo Daime
Santo Daime () is a syncretic religion founded in the 1930s in the Brazilian Amazonian state of Acre by Raimundo Irineu Serra, known as Mestre Irineu. Santo Daime incorporates elements of several religious or spiritual traditions including Folk ...
churches filed suit in federal court to gain legal status to import DMT-containing
ayahuasca
AyahuascaPronounced as in the UK and in the US. Also occasionally known in English as ''ayaguasca'' ( Spanish-derived), ''aioasca'' (Brazilian Portuguese-derived), or as ''yagé'', pronounced or . Etymologically, all forms but ''yagé'' desce ...
tea. The case, ''
Church of the Holy Light of the Queen v. Mukasey'', presided over by Judge
Owen M. Panner
Owen Murphy Panner (July 28, 1924 – December 19, 2018) was an American attorney and jurist from Oregon who served as a United States district judge of the United States District Court for the District of Oregon.
Early life
Panner was born in ...
, 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
Freedom of religion or religious liberty is a principle that supports the freedom of an individual or community, in public or private, to manifest religion or belief in teaching, practice, worship, and observance. It also includes the freed ...
. His order prohibits the federal government from interfering with and prosecuting church members who follow a list of regulations set out in his order.
Oceania
*
New Zealand
New Zealand ( mi, Aotearoa ) is an island country in the southwestern Pacific Ocean. It consists of two main landmasses—the North Island () and the South Island ()—and over 700 smaller islands. It is the sixth-largest island count ...
– DMT is classified as a Class A drug under the
Misuse of Drugs Act 1975
The Misuse of Drugs Act 1975 is a New Zealand drug control law that classifies drugs into three classes, or schedules, purportedly based on their projected risk of serious harm. However, in reality, classification of drugs outside of passing law ...
.
*
Australia – DMT is listed as a Schedule 9 prohibited substance in
Australia under the
Poisons Standard (October 2015).
[Poisons Standard October 201]
comlaw.gov.au
/ref> A schedule 9 drug is outlined in the Poisons Act 1964
Poison is a chemical substance that has a detrimental effect to life. The term is used in a wide range of scientific fields and industries, where it is often specifically defined. It may also be applied colloquially or figuratively, with a broa ...
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." Between 2011 and 2012, the Australian Federal Government
The Australian Government, also known as the Commonwealth Government, is the national government of Australia, a federal parliamentary constitutional monarchy. Like other Westminster-style systems of government, the Australian Government ...
was considering changes to the Australian Criminal Code that would classify any plants containing any amount of DMT as "controlled plants". 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
''Acacia pycnantha'', most commonly known as the golden wattle, is a tree of the family Fabaceae native to southeastern Australia. It grows to a height of and has phyllodes (flattened leaf stalks) instead of true leaves. Sickle-shaped, these ...
(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). 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.
Chemistry
DMT is commonly handled and stored as a hemifumarate, as other DMT acid salts are extremely hygroscopic
Hygroscopy is the phenomenon of attracting and holding water molecules via either absorption or adsorption from the surrounding environment, which is usually at normal or room temperature. If water molecules become suspended among the substan ...
and will not readily crystallize. Its freebase
Freebase may refer to:
*Free base or freebase, the pure basic form of an amine, as opposed to its salt form
*Freebase (database), a former online database service
*Freebase (mixtape), ''Freebase'' (mixtape), 2014 mixtape by 2 Chainz
*An original ...
form, although less stable than DMT hemifumarate, is favored by recreational users choosing to vaporize the chemical as it has a lower boiling point.
Biosynthesis
Dimethyltryptamine is an indole alkaloid
Indole alkaloids are a class of alkaloids containing a structural moiety of indole; many indole alkaloids also include isoprene groups and are thus called terpene indole or secologanin tryptamine alkaloids. Containing more than 4100 known diffe ...
derived from the shikimate
Shikimic acid, more commonly known as its anionic form shikimate, is a cyclohexene, a cyclitol and a cyclohexanecarboxylic acid. It is an important biochemical metabolite in plants and microorganisms. Its name comes from the Japanese flower ''s ...
pathway. Its biosynthesis is relatively simple and summarized in the adjacent picture. In plants, the parent amino acid L-tryptophan
Tryptophan (symbol Trp or W)
is an α-amino acid that is used in the biosynthesis of proteins. Tryptophan contains an Alpha_and_beta_carbon , α-amino group, an α-carboxylic acid group, and a side chain indole, making it a polar molecule with ...
is produced endogenously where in animals L-tryptophan
Tryptophan (symbol Trp or W)
is an α-amino acid that is used in the biosynthesis of proteins. Tryptophan contains an Alpha_and_beta_carbon , α-amino group, an α-carboxylic acid group, and a side chain indole, making it a polar molecule with ...
is an essential amino acid
An essential amino acid, or indispensable amino acid, is an amino acid that cannot be synthesized from scratch by the organism fast enough to supply its demand, and must therefore come from the diet. Of the 21 amino acids common to all life form ...
coming from diet. No matter the source of L-tryptophan
Tryptophan (symbol Trp or W)
is an α-amino acid that is used in the biosynthesis of proteins. Tryptophan contains an Alpha_and_beta_carbon , α-amino group, an α-carboxylic acid group, and a side chain indole, making it a polar molecule with ...
, the biosynthesis begins with its decarboxylation by an aromatic amino acid decarboxylase
Aromatic L-amino acid decarboxylase (AADC or AAAD), also known as DOPA decarboxylase (DDC), tryptophan decarboxylase, and 5-hydroxytryptophan decarboxylase, is a lyase enzyme (), located in region 7p12.2-p12.1.
Mechanism
The enzyme uses pyrid ...
(AADC) enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
(step 1). The resulting decarboxylated tryptophan analog
Analog or analogue may refer to:
Computing and electronics
* Analog signal, in which information is encoded in a continuous variable
** Analog device, an apparatus that operates on analog signals
*** Analog electronics, circuits which use analog ...
is tryptamine
Tryptamine is an indolamine metabolite of the essential amino acid, tryptophan. The chemical structure is defined by an indole ─ a fused benzene and pyrrole ring, and a 2-aminoethyl group at the second carbon (third aromatic atom, with the f ...
. Tryptamine then undergoes a transmethylation (step 2): the enzyme indolethylamine-N-methyltransferase (INMT) catalyzes the transfer of a methyl group
In organic chemistry, a methyl group is an alkyl derived from methane, containing one carbon atom bonded to three hydrogen atoms, having chemical formula . In formulas, the group is often abbreviated as Me. This hydrocarbon group occurs in ma ...
from cofactor S-adenosyl-methionine (SAM), via nucleophilic
In chemistry, a nucleophile is a chemical species that forms bonds by donating an electron pair. All molecules and ions with a free pair of electrons or at least one pi bond can act as nucleophiles. Because nucleophiles donate electrons, they are ...
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 radiolabeling
A radioactive tracer, radiotracer, or radioactive label is a chemical compound in which one or more atoms have been replaced by a radionuclide so by virtue of its radioactive decay it can be used to explore the mechanism of chemical reactions by ...
of SAM methyl group with carbon-14 (14C-CH3)SAM.
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
Indole is an aromatic heterocyclic organic compound
In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other c ...
with oxalyl chloride
Oxalyl chloride is an organic chemical compound with the formula (COCl)2. This colorless, sharp-smelling liquid, the diacyl chloride of oxalic acid, is a useful reagent in organic synthesis.
Preparation
Oxalyl chloride was first prepared in 1892 ...
followed by reaction with dimethylamine
Dimethylamine is an organic compound with the formula (CH3)2NH. This secondary amine is a colorless, flammable gas with an ammonia-like odor. Dimethylamine is commonly encountered commercially as a solution in water at concentrations up to aroun ...
and reduction of the carbonyl functionalities with lithium aluminum hydride
Lithium aluminium hydride, commonly abbreviated to LAH, is an inorganic compound with the chemical formula Li Al H4. It is a white solid, discovered by Finholt, Bond and Schlesinger in 1947. This compound is used as a reducing agent in organic sy ...
to form DMT. 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. 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. Bufotenine, a plant extract, can also be synthesized into DMT. 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
In a clandestine setting, DMT is not typically synthesized due to the lack of availability of the starting materials, namely tryptamine
Tryptamine is an indolamine metabolite of the essential amino acid, tryptophan. The chemical structure is defined by an indole ─ a fused benzene and pyrrole ring, and a 2-aminoethyl group at the second carbon (third aromatic atom, with the f ...
and oxalyl chloride
Oxalyl chloride is an organic chemical compound with the formula (COCl)2. This colorless, sharp-smelling liquid, the diacyl chloride of oxalic acid, is a useful reagent in organic synthesis.
Preparation
Oxalyl chloride was first prepared in 1892 ...
. Instead, it is more often extracted from plant sources using a non-polar hydrocarbon solvent such as naphtha
Naphtha ( or ) is a flammable liquid hydrocarbon mixture.
Mixtures labelled ''naphtha'' have been produced from natural gas condensates, petroleum distillates, and the distillation of coal tar and peat. In different industries and regions ' ...
or heptane
Heptane or ''n''-heptane is the straight-chain alkane with the chemical formula H3C(CH2)5CH3 or C7H16. When used as a test fuel component in anti-knock test engines, a 100% heptane fuel is the zero point of the octane rating scale (the 100 poin ...
, 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, but specific plants such as ''Mimosa tenuiflora
''Mimosa tenuiflora'', syn. ''Mimosa hostilis'', also known as jurema preta, calumbi (Brazil), tepezcohuite (México), carbonal, cabrera, jurema, black jurema, and binho de jurema, is a perennial tree or shrub native to the northeastern region of ...
, Acacia Acuminata
''Acacia acuminata'', known as mangart and jam, is a tree in the family Fabaceae. Endemic to Western Australia, it occurs throughout the south west of the State. It is common in the Wheatbelt, and also extends into the semi-arid interior.
...
'' and ''Acacia confusa
''Acacia confusa'' is a perennial tree native to South-East Asia. Some common names for it are acacia petit feuille, Ayangile, small Philippine acacia, Formosa acacia (Taiwan acacia), Philippine Wattle, and Formosan koa. It grows to a height of 1 ...
'' 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
Science is a systematic endeavor that Scientific method, builds and organizes knowledge in the form of Testability, testable explanations and predictions about the universe.
Science may be as old as the human species, and some of the earli ...
'' in 1961, Julius Axelrod
Julius Axelrod (May 30, 1912 – December 29, 2004) was an American biochemist. He won a share of the Nobel Prize in Physiology or Medicine in 1970 along with Bernard Katz and Ulf von Euler. The Nobel Committee honored him for his work on the re ...
found an ''N''-methyltransferase
Methyltransferases are a large group of enzymes that all methylate their substrates but can be split into several subclasses based on their structural features. The most common class of methyltransferases is class I, all of which contain a Ross ...
enzyme capable of mediating biotransformation of tryptamine into DMT in a rabbit's lung. This finding 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: localization and further characterization of the ''N''-methyltransferase enzyme, and analytical studies looking for endogenously produced DMT in body fluids and tissues.
In 2013, researchers reported DMT in the pineal gland microdialysate of rodents.
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.
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
A near-death experience (NDE) is a profound personal experience associated with death or impending death which researchers claim share similar characteristics. When positive, such experiences may encompass a variety of sensations including detac ...
.
In 2014, researchers demonstrated the immunomodulatory potential of DMT and 5-MeO-DMT
5-MeO-DMT (5-methoxy-''N'',''N''-dimethyltryptamine) or O-methyl-bufotenin is a psychedelic of the tryptamine class. It is found in a wide variety of plant species, and also is secreted by the glands of at least one toad species, the Colorado R ...
through the Sigma-1 receptor
The sigma-1 receptor (σ1R), one of two sigma receptor subtypes, is a chaperone protein at the endoplasmic reticulum (ER) that modulates calcium signaling through the IP3 receptor. In humans, the σ1 receptor is encoded by the ''SIGMAR1'' gen ...
of human immune cells. This immunomodulatory activity may contribute to significant anti-inflammatory effects and tissue regeneration.
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.
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
A structural analog (analogue in modern traditional English; Commonwealth English), also known as a chemical analog or simply an analog, is a compound having a structure similar to that of another compound, but differing from it in respect to a c ...
bufotenin (5-HO-DMT), in human blood and urine. In an article published four months later, the method used in their study was strongly criticized, and the credibility of their results challenged.
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. 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
In chemical analysis, chromatography is a laboratory technique for the separation of a mixture into its components. The mixture is dissolved in a fluid solvent (gas or liquid) called the ''mobile phase'', which carries it through a system (a ...
-tandem mass spectrometry
Tandem mass spectrometry, also known as MS/MS or MS2, is a technique in instrumental analysis where two or more mass analyzers are coupled together using an additional reaction step to increase their abilities to analyse chemical samples. A com ...
with electrospray ionization
Electrospray ionization (ESI) is a technique used in mass spectrometry to produce ions using an electrospray in which a high voltage is applied to a liquid to create an aerosol. It is especially useful in producing ions from macromolecules becaus ...
(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
Cerebrospinal fluid (CSF) is a clear, colorless body fluid found within the tissue that surrounds the brain and spinal cord of all vertebrates.
CSF is produced by specialised ependymal cells in the choroid plexus of the ventricles of the ...
; LOD = limit of detection
The limit of detection (LOD or LoD) is the lowest signal, or the lowest corresponding quantity to be determined (or extracted) from the signal, that can be observed with a sufficient degree of confidence or statistical significance. However, the ...
; n = number of samples; ng/L and ng/kg = nanograms (10−9 g) per litre, and nanograms per kilogram, respectively):
A 2013 study found DMT in microdialysate obtained from a rat's pineal gland, providing evidence of endogenous DMT in the mammalian brain. 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.
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.
INMT
Before techniques of molecular biology
Molecular biology is the branch of biology that seeks to understand the molecular basis of biological activity in and between cells, including biomolecular synthesis, modification, mechanisms, and interactions. The study of chemical and physi ...
were used to localize indolethylamine ''N''-methyltransferase (INMT), characterization and localization went on a par: samples of the biological material where INMT is hypothesized to be active are subject to enzyme assay
Enzyme assays are laboratory methods for measuring enzymatic activity. They are vital for the study of enzyme kinetics and enzyme inhibition.
Enzyme units
The quantity or concentration of an enzyme can be expressed in molar amounts, as with a ...
. 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 or with addition of a radiolabeled substrate like (14C)NMT to demonstrate in vivo
Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and ...
formation. 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
Thin-layer chromatography (TLC) is a chromatography technique used to separate non-volatile mixtures.
Thin-layer chromatography is performed on a sheet of an inert substrate such as glass, plastic, or aluminium foil, which is coated with a t ...
(TLC) was thus used in a vast majority of studies. 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 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 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. 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
Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and ...
, 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
Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and ...
INMT activity and DMT production in brain (rat) with TLC methods finds biotransformation of radiolabeled 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 localize INMT, a qualitative leap is accomplished with use of modern techniques of molecular biology
Molecular biology is the branch of biology that seeks to understand the molecular basis of biological activity in and between cells, including biomolecular synthesis, modification, mechanisms, and interactions. The study of chemical and physi ...
, and of immunohistochemistry. In humans, a gene encoding INMT is determined to be located on chromosome 7
Chromosome 7 is one of the 23 pairs of chromosomes in humans, who normally have two copies of this chromosome. Chromosome 7 spans about 159 million base pairs (the building material of DNA) and represents between 5 and 5.5 percent of the total D ...
. Northern blot analyses reveal INMT messenger RNA (mRNA) to be highly expressed in rabbit lung, and in human thyroid
The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans it is in the neck and consists of two connected lobes. The lower two thirds of the lobes are connected by a thin band of tissue called the thyroid isthmus. The thy ...
, adrenal gland
The adrenal glands (also known as suprarenal glands) are endocrine glands that produce a variety of hormones including adrenaline and the steroids aldosterone and cortisol. They are found above the kidneys. Each gland has an outer cortex whic ...
, 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
The thymus is a specialized primary lymphoid organ of the immune system. Within the thymus, thymus cell lymphocytes or ''T cells'' mature. T cells are critical to the adaptive immune system, where the body adapts to specific foreign invaders. ...
, liver, spleen
The spleen is an organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The word spleen comes . , kidney, colon, ovary, and bone marrow. INMT mRNA expression is absent in human peripheral blood leukocytes
White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mult ...
, whole brain, and in tissue from 7 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. In 2011, immunohistochemistry revealed the presence of INMT in primate nervous tissue including retina, spinal cord motor neurons, and pineal gland. 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.
Pharmacology
Pharmacokinetics
DMT peak level concentrations (''C''max) 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 concentration
Molar concentration (also called molarity, amount concentration or substance concentration) is a measure of the concentration of a chemical species, in particular of a solute in a solution, in terms of amount of substance per unit volume of sol ...
s 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 (''T''max) 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
AyahuascaPronounced as in the UK and in the US. Also occasionally known in English as ''ayaguasca'' ( Spanish-derived), ''aioasca'' (Brazilian Portuguese-derived), or as ''yagé'', pronounced or . Etymologically, all forms but ''yagé'' desce ...
decoction, and in freeze-dried
Freeze drying, also known as lyophilization or cryodesiccation, is a low temperature dehydration process that involves freezing the product and lowering pressure, removing the ice by sublimation. This is in contrast to dehydration by most conve ...
ayahuasca gel caps, DMT ''T''max is considerably delayed: 107.59 ± 32.5 minutes, and 90–120 minutes, respectively.
The pharmacokinetics for vaporizing DMT have not been studied or reported.
Neurogenesis
In September 2020, an ''in vitro
''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called " test-tube experiments", these studies in biology ...
'' and ''in vivo
Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and ...
'' study showed that DMT present in the ayahuasca infusion promotes neurogenesis.
Pharmacodynamics
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's 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
Valvular heart disease is any cardiovascular disease process involving one or more of the four valves of the heart (the aortic and mitral valves on the left side of heart and the pulmonic and tricuspid valves on the right side of heart). These ...
.
It has also been shown to possess affinity for the dopamine D1, α1-adrenergic, α2-adrenergic, imidazoline-1, and σ1 receptors
Receptor may refer to:
*Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse
*Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a n ...
. 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
The serotonin transporter (SERT or 5-HTT) also known as the sodium-dependent serotonin transporter and solute carrier family 6 member 4 is a protein that in humans is encoded by the SLC6A4 gene. SERT is a type of monoamine transporter protein tha ...
(SERT) expressed in human platelets, and the rat vesicular monoamine transporter 2
The solute carrier family 18 member 2 (SLC18A2) also known as vesicular monoamine transporter 2 (VMAT2) is a protein that in humans is encoded by the ''SLC18A2'' gene. SLC18A2 is an integral membrane protein that transports monoamines—partic ...
(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.
As with other so-called "classical hallucinogens", a large part of DMT psychedelic effects can be attributed to a functionally selective 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 (see Pharmacokinetics).
As DMT has been shown to have slightly better efficacy (EC50) at human serotonin 2C receptor than at the 2A receptor, 5-HT2C is also likely implicated in DMT's overall effects. Other receptors, such as 5-HT1A σ1, may also play a role.
In 2009, it was hypothesized that DMT may be an endogenous ligand
In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. The etymology stems from ''ligare'', which means 'to bind'. In protein-ligand binding, the ligand is usually a m ...
for the σ1 receptor. The concentration of DMT needed for σ1 activation ''in vitro'' (50–100 μM) is similar to the behaviorally active concentration measured in mouse brain
The mouse brain refers to the brain of Mus musculus. Various brain atlases exist.
For reasons of reproducibility, genetically characterized, stable strains like C57BL/6 were chosen to produce high-resolution images and databases. Well known onl ...
of approximately 106 μM 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, 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.
Society and culture
Black market
Electronic cigarette cartridges filled with DMT started to be sold on the black market in 2018.
See also
* DMT-N-oxide
* Psychedelic drug
* List of psychoactive plants
This is a list of plant species that, when consumed by humans, are known or suspected to produce psychoactive effects: changes in nervous system function that alter perception, mood, consciousness, cognition or behavior. Many of these plants ...
* MPMI
* Serotonergic psychedelic
Psychedelics are a subclass of hallucinogenic drugs whose primary effect is to trigger non-ordinary states of consciousness (known as psychedelic experiences or "trips").Pollan, Michael (2018). ''How to Change Your Mind: What the New Science of ...
* Psychoplastogen
* Alexander Shulgin
* SN-22
* Rick Strassman
Rick Strassman is an American clinical associate professor of psychiatry at the University of New Mexico School of Medicine. He has held a fellowship in clinical psychopharmacology research at the University of California San Diego and was Profess ...
References
External links
DMT chapter from ''TiHKAL''
* St John, Graham. 2015
''Mystery School in Hyperspace: A Cultural History of DMT.''
Berkeley, CA.: North Atlantic Books. .
{{DEFAULTSORT:Dimethyltryptamine
Ayahuasca
Entheogens
Tryptamine alkaloids
Psychedelic tryptamines
Serotonin receptor agonists
Dimethylamino compounds