DMT: Difference between revisions

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{{MedTemplate

| generic = DMT

| brand =

| structure =

| classes = Classic Psychedelic, Tryptamine

| classes = [[:Category:Classical Psychedelics (Serotonergic)|Classic Psychedelic]], [[:Category:Tryptamines|Tryptamine]]

| mechanism = 5-HT2A agonist; sigma-1 ~~receptor~~ agonist

| uses =

| ~~uses~~ =

| starting_dose =

| ~~starting_dose~~ =

| preparations =

| ~~preparations~~ =

| fda_max =

| ~~fda_max~~ =

| pill_id =

| ~~routes~~ =

| routes =

| ~~onset~~ =

| onset =

| ~~duration~~ =

| duration = About 20 minutes

| ~~halflife~~ =

| halflife = 9–12 minutes (intravenous)

| ~~bioavailability~~ =

| bioavailability =

| ~~pregnancy~~ =

| pregnancy =

| legal =

| legal = [[USLegal:DEA Schedule I|Schedule I]] (United States)

| ~~intro~~ =

| mechanism = 5-HT2A partial agonist; sigma-1 agonist

| ~~pharmacokinetics~~ =

| intro = The earliest record of human use of DMT-bearing medicines comes from the Amazon and the Orinoco, where indigenous peoples have for centuries prepared visionary preparations from plants that contain the molecule. The most widespread of these is [[Ayahuasca|ayahuasca]], a brew of the [[Banisteriopsis caapi]] vine cooked together with the leaves of [[Psychotria viridis]] or related DMT-bearing companions. The vine contains [[Harmine|harmine]] and [[Harmaline|harmaline]], which inhibit [[Monoamine oxidase|monoamine oxidase]] and allow orally administered DMT, which would otherwise be destroyed in the gut, to reach the brain. The pairing is the technical accomplishment that defines the tradition. Whether indigenous knowledge of the pairing predates European contact in its present form is debated by ethnobotanists, but the brew was encountered by missionaries in the upper Amazon in the 19th century and entered ethnographic literature through [[Richard Spruce]]'s botanical work in the 1850s and, later, through [[Richard Evans Schultes]] at the Harvard Botanical Museum.<ref name="schultes1969">Schultes RE. Hallucinogens of plant origin. Science. 1969;163(3864):245-254. PMID: 4883616.</ref>

| ~~pharmacodynamics~~ =

| ~~indications~~ =

{{PendellsCorner

| ~~dosing~~ =

| quote = In the old days, for pot-smokers and acid heads, there was pot, there was acid, and then, beyond them all, there was DMT.

| effects =

| volume = Gnosis

| ~~contraindications~~ =

| page = 227

| ~~interactions~~ =

}}

| ~~pregnancy_details~~ =

| ~~monitoring~~ =

The other major lineage is the snuffs. [[Anadenanthera peregrina]] and [[Anadenanthera colubrina]], leguminous trees of the South American lowlands, yield seeds that indigenous peoples have ground, toasted, and inhaled as the snuffs [[Cohoba|cohoba]] and [[Yopo|yopo]]. Cohoba was reported by the Spanish chronicler Ramón Pané at Hispaniola in 1496, in an account commissioned by Columbus, making the European written record of DMT-bearing medicine more than four centuries old.

| ~~counseling~~ =

| ~~anecdotes~~ =

{{ShulginsCorner

| seealso =

| quote = There is a drug (chemistry), and a plant (botany) that produces an effect (pharmacology) in some people out there (anthropology) that might have some healing use (medicine) or some spiritual impact (theology).

| references =

| volume = TiHKAL

| page = p. 247

| voice = Commentary

}}

| history = The chemistry came much later. The molecule itself was first synthesized in 1931 by the Canadian chemist [[Richard Helmuth Frederick Manske]] at the National Research Council laboratories in Ottawa, as part of a systematic study of the methyltryptamines.<ref name="manske1931">Manske RHF. A synthesis of the methyltryptamines and some derivatives. Canadian Journal of Research. 1931;5:592-600.</ref> At the time, no one knew the compound occurred in any plant. The natural-product identification came in 1946, when the Brazilian chemist [[Oswaldo Gonçalves de Lima]] isolated an alkaloid he called nigerine from the roots of [[Mimosa hostilis]], the plant used in the northeastern Brazilian preparation known as the wine of jurema.<ref name="lima1946">Gonçalves de Lima O. Observações sobre o "vinho da Jurema" utilizado pelos índios Pancarú de Tacaratú (Pernambuco). Arquivos do Instituto de Pesquisas Agronômicas. 1946;4:45-80.</ref> Nigerine was later shown to be DMT. In 1955, M. S. Fish, N. M. Johnson, and E. C. Horning identified DMT and related tryptamines as the active constituents of Anadenanthera peregrina seeds, finally connecting the 500-year-old cohoba record to the molecule.<ref name="fish1955">Fish MS, Johnson NM, Horning EC. Piptadenia alkaloids. Indole bases of P. peregrina (L.) Benth. and related species. Journal of the American Chemical Society. 1955;77(22):5892-5895.</ref>

{{ShulginsCorner

| quote = Are "natural" drugs inherently safer or better than synthetic drugs? DMT was first synthesized in the laboratory and remained a "synthetic" drug for a couple of decades until it was identified from a plant source. Then, of course, it became a "natural" drug. Nothing changed except for the positions taken by the advocates on the two sides.

| volume = TiHKAL

| page = p. 278

| voice = Commentary

}}

The proof that DMT was psychoactive in humans is owed to [[Stephen Szára]]. A young Hungarian chemist and psychiatrist working in Budapest in the mid-1950s, Szára was studying the model-psychosis hypothesis and wanted to work with [[LSD]]. He wrote to Sandoz in Basel and was refused. Sandoz declined to send a powerful psychotropic compound across the Iron Curtain, fearing it would reach Communist hands. Szára turned instead to a molecule he could synthesize himself, and in 1956 administered DMT intramuscularly to a series of healthy volunteers, mostly young physician colleagues. The effects, brief, intense, and unmistakably psychedelic, were published the same year in Experientia.<ref name="szara1956">Szára S. Dimethyltryptamin: its metabolism in man; the relation to its psychotic effect to the serotonin metabolism. Experientia. 1956;12(11):441-442. PMID: 13384414.</ref> After the Hungarian uprising later that year, Szára emigrated, eventually joining the National Institute of Mental Health in the United States, where he and colleagues characterized DMT alongside its diethyl and dipropyl homologs.

{{ShulginsCorner

| quote = To some users, it is a connection to a vivid world of magic and mystical beings. To others, it is a dark exposure to the most negative aspects of the psyche. And everything in-between.

| volume = TiHKAL

| page = p. 249

| voice = Commentary

}}

The clinical-research era that followed was abbreviated by prohibition. In the United States, the [[Controlled Substances Act]] of 1970 placed DMT in Schedule I, the most restrictive category, and human research effectively ceased for two decades. The reopening came in the early 1990s, when [[Rick Strassman]] obtained the regulatory permissions required to administer intravenous DMT to healthy volunteers at the University of New Mexico. Strassman's group published the first modern dose-response work in 1994, characterizing the neuroendocrine, autonomic, and subjective effects of the molecule and reviving the field.<ref name="strassman1994a">Strassman RJ, Qualls CR. Dose-response study of N,N-dimethyltryptamine in humans. I. Neuroendocrine, autonomic, and cardiovascular effects. Archives of General Psychiatry. 1994;51(2):85-97. PMID: 8297216.</ref><ref name="strassman1994b">Strassman RJ, Qualls CR, Uhlenhuth EH, Kellner R. Dose-response study of N,N-dimethyltryptamine in humans. II. Subjective effects and preliminary results of a new rating scale. Archives of General Psychiatry. 1994;51(2):98-108. PMID: 8297217.</ref>

{{PendellsCorner

| quote = Deep psychonauts of DMT space usually agree that it is very difficult to bring anything back from the space, or to talk about it in any way with someone who hasn't been there.

| volume = Gnosis

| page = 227

}}

The legal status of DMT-bearing preparations has been litigated as well as legislated. In 2006, the United States Supreme Court ruled unanimously in Gonzales v. O Centro Espírita Beneficente União do Vegetal that the federal government could not bar the União do Vegetal, a Brazilian-origin religious community, from sacramental use of ayahuasca within the United States, applying the Religious Freedom Restoration Act. The decision opened a narrow legal channel for ayahuasca use that remains in place.

{{PendellsCorner

| quote = DMT is now known to be widespread in the plant world, particularly in the grasses and the pea family. In trace amounts, as Alexander Shulgin titled a chapter in TIHKAL, "DMT is everywhere." It is also found in the human body, and in the human brain.

| volume = Gnosis

| page = 229

}}

The endogenous question runs alongside the human-use history. DMT was identified in human urine in 1965 and in human blood and cerebrospinal fluid in the years that followed; it is now established as a normal, trace constituent of the mammalian body, though its physiological role remains the subject of active investigation.<ref name="barker2018">Barker SA. N,N-Dimethyltryptamine (DMT), an Endogenous Hallucinogen. Frontiers in Neuroscience. 2018;12:536. PMID: 30127713.</ref> The molecule's presence in the brain has driven a long-running and unresolved discussion about whether endogenous DMT contributes to ordinary or pathological states of consciousness, a question that became prominent during the modern research renaissance.

{{ShulginsCorner

| quote = DMT is, most simply, almost everywhere you choose to look. It is in this flower here, in that tree over there, and in yonder animal.

| volume = TiHKAL

| page = p. 249

| voice = Commentary

}}

That renaissance has continued. Exploratory clinical work in the 2020s has examined intravenous DMT in healthy volunteers and in patients with major depressive disorder.<ref name="dsouza2022">D'Souza DC, Syed SA, Flynn LT, Safi-Aghdam H, et al. Exploratory study of the dose-related safety, tolerability, and efficacy of dimethyltryptamine (DMT) in healthy volunteers and major depressive disorder. Neuropsychopharmacology. 2022;47(10):1854-1862. PMID: 35660802.</ref> The compound's very short duration of action, roughly twenty minutes when given by inhalation or intravenous infusion, has driven interest in formulations and infusion schemes designed to extend or control the experience for therapeutic purposes.

{{PendellsCorner

| quote = The main problem of DMT art, aside from the ubiquitous presence of spiritual clichés, is its embarrassing obviousness. Subtlety is not one of DMT's qualities.

| volume = Gnosis

| page = 233

}}

DMT is not currently licensed as a medicine in any major jurisdiction. Clinical investigation is active in major depressive disorder, with phase I and II trials of intravenous formulations underway. Ayahuasca, the orally active preparation, has been studied in a randomized placebo-controlled trial for treatment-resistant depression, with rapid antidepressant effects reported at follow-up.<ref name="palhanofontes2019">Palhano-Fontes F, Barreto D, Onias H, Andrade KC, et al. Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial. Psychological Medicine. 2019;49(4):655-663. PMID: 29903051.</ref> Outside of formal trials, DMT-containing preparations are used in religious and ceremonial settings under varying legal frameworks.

{{ShulginsCorner

| quote = Mushrooms are everywhere, and frogs are everywhere. And DMT is almost everywhere. They just don't happen to be in the same everywhere.

| volume = TiHKAL

| page = p. 256

| voice = Commentary

}}

DMT is a Schedule I controlled substance in the United States and is similarly restricted under the 1971 United Nations Convention on Psychotropic Substances. The Gonzales v. O Centro decision (2006) established a religious-use exemption for the União do Vegetal; the Santo Daime church has subsequently obtained similar exemptions in several jurisdictions. Brazil, the country of the ayahuasca traditions, has permitted religious use of the brew since the late 1980s.

{{PendellsCorner

| quote = And a bit of whatever the place is where magic lives. All adding up to a very spicy and seductive song. THERE IS MEANING HERE. THE SECRET IS HERE.

| volume = Gnosis

| page = 236

}}

| effects =

'''Physical'''

* <effect ref="changes-in-felt-bodily-form" author="MDElliottMD"/>

* <effect ref="increased-heart-rate" author="MDElliottMD"/>

* <effect ref="increased-blood-pressure" author="MDElliottMD"/>

* <effect ref="neurogenesis" author="MDElliottMD"/>

* <effect ref="neuroplasticity" author="MDElliottMD"/>

* <effect ref="pupil-dilation" author="MDElliottMD"/>

* <effect ref="physical-autonomy" author="MDElliottMD"/>

* <effect ref="spatial-disorientation" author="MDElliottMD"/>

* <effect ref="temperature-regulation-suppression" author="MDElliottMD"/>

* <effect ref="spontaneous-bodily-sensations" author="MDElliottMD"/>

* <effect ref="physical-euphoria" author="MDElliottMD"/>

* <effect ref="changes-in-felt-gravity" author="MDElliottMD"/>

* <effect ref="nausea" author="MDElliottMD"/>

* <effect ref="increased-libido" author="MDElliottMD"/>

* <effect ref="seizure" author="MDElliottMD"/>

'''Visual'''

* <effect ref="color-enhancement" author="MDElliottMD"/>

* <effect ref="pattern-recognition-enhancement" author="MDElliottMD"/>

* <effect ref="visual-acuity-enhancement" author="MDElliottMD"/>

* <effect ref="magnification" author="MDElliottMD"/>

* <effect ref="drifting" author="MDElliottMD"/>

* <effect ref="color-replacement" author="MDElliottMD"/>

* <effect ref="color-shifting" author="MDElliottMD"/>

* <effect ref="color-tinting" author="MDElliottMD"/>

* <effect ref="tracers" author="MDElliottMD"/>

* <effect ref="after-images" author="MDElliottMD"/>

* <effect ref="recursion" author="MDElliottMD"/>

* <effect ref="scenery-slicing" author="MDElliottMD"/>

* <effect ref="symmetrical-texture-repetition" author="MDElliottMD"/>

* <effect ref="environmental-patterning" author="MDElliottMD"/>

* <effect ref="geometry" author="MDElliottMD"/>

* <effect ref="machinescapes" author="MDElliottMD"/>

* <effect ref="transformations" author="MDElliottMD"/>

* <effect ref="internal-hallucination" author="MDElliottMD"/>

* <effect ref="external-hallucination" author="MDElliottMD"/>

'''Cognitive'''

* <effect ref="anxiety" author="MDElliottMD"/>

* <effect ref="feelings-of-impending-doom" author="MDElliottMD"/>

* <effect ref="d-j-vu" author="MDElliottMD"/>

* <effect ref="delusion" author="MDElliottMD"/>

* <effect ref="ego-replacement" author="MDElliottMD"/>

* <effect ref="emotion-intensification" author="MDElliottMD"/>

* <effect ref="empathy-affection-and-sociability-enhancement" author="MDElliottMD"/>

* <effect ref="euthymia" author="MDElliottMD"/>

* <effect ref="catharsis" author="MDElliottMD"/>

* <effect ref="analysis-enhancement" author="MDElliottMD"/>

* <effect ref="creativity-enhancement" author="MDElliottMD"/>

* <effect ref="immersion-intensification" author="MDElliottMD"/>

* <effect ref="cognitive-euphoria" author="MDElliottMD"/>

* <effect ref="increased-music-appreciation" author="MDElliottMD"/>

* <effect ref="memory-enhancement" author="MDElliottMD"/>

* <effect ref="memory-suppression" author="MDElliottMD"/>

* <effect ref="ego-death" author="MDElliottMD"/>

* <effect ref="mindfulness" author="MDElliottMD"/>

* <effect ref="multiple-thought-streams" author="MDElliottMD"/>

* <effect ref="novelty-enhancement" author="MDElliottMD"/>

* <effect ref="personal-bias-suppression" author="MDElliottMD"/>

* <effect ref="suggestibility-intensification" author="MDElliottMD"/>

* <effect ref="rejuvenation" author="MDElliottMD"/>

* <effect ref="appetite-suppression" author="MDElliottMD"/>

* <effect ref="decreased-libido" author="MDElliottMD"/>

* <effect ref="autonomous-voice-communication" author="MDElliottMD"/>

* <effect ref="conceptual-thinking" author="MDElliottMD"/>

* <effect ref="thought-acceleration" author="MDElliottMD"/>

* <effect ref="thought-connectivity" author="MDElliottMD"/>

* <effect ref="thought-organization" author="MDElliottMD"/>

* <effect ref="time-distortion" author="MDElliottMD"/>

* <effect ref="wakefulness" author="MDElliottMD"/>

'''Auditory'''

* <effect ref="auditory-acuity-enhancement" author="MDElliottMD"/>

* <effect ref="auditory-distortion" author="MDElliottMD"/>

* <effect ref="auditory-hallucination" author="MDElliottMD"/>

'''Multi-sensory'''

* <effect ref="synaesthesia" author="MDElliottMD"/>

'''Transpersonal'''

* <effect ref="spirituality-intensification" author="MDElliottMD"/>

* <effect ref="existential-self-realization" author="MDElliottMD"/>

* <effect ref="near-death-experience" author="MDElliottMD"/>

* <effect ref="perception-of-eternalism" author="MDElliottMD"/>

* <effect ref="perception-of-self-design" author="MDElliottMD"/>

* <effect ref="perceived-exposure-to-inner-mechanics-of-consciousness" author="MDElliottMD"/>

* <effect ref="unity-and-interconnectedness" author="MDElliottMD"/>

<small>Subjective-effect profile adapted from [https://psychonautwiki.org/wiki/DMT PsychonautWiki], CC BY-SA 4.0.</small>

| pharmacodynamics = {{PendellsCorner

| quote = There are fibers of geometry that dumbfound even sailors.

| volume = Gnosis

| page = 235

}}

DMT is a substituted [[:Category:Tryptamines|tryptamine]] whose effects in the central nervous system are mediated primarily by partial agonism at the serotonin 5-HT2A receptor, with additional activity at other 5-HT receptor subtypes and, at higher concentrations, at sigma-1 and trace amine-associated receptors.<ref name="nichols2016">Nichols DE. Psychedelics. Pharmacological Reviews. 2016;68(2):264-355. PMID: 26841800.</ref> Taken orally without an accompanying inhibitor, DMT is inactive: monoamine oxidase A in the gut and liver metabolizes it before it reaches the brain. Inhalation, insufflation, or parenteral administration bypass this first-pass destruction, as does oral co-administration with a [[:Category:Monoamine Oxidase Inhibitors (MAOIs)|monoamine oxidase inhibitor]], which is the pharmacological logic of ayahuasca. Plasma elimination half-life after intravenous administration is approximately 9 to 12 minutes, among the shortest of any psychoactive medicine in clinical use.

Doses used outside the research setting are not standardized. Harm-reduction documentation such as the Erowid DMT Vault records inhaled use ranging from a few milligrams to roughly sixty milligrams, with effects beginning within about a minute and largely resolving within twenty minutes.<ref name="erowid-dmt-dose">Erowid. DMT Dosage. Erowid DMT Vault, 1997, last modified 21 February 2015. https://www.erowid.org/chemicals/dmt/dmt_dose.shtml (accessed 21 May 2026).</ref> Because DMT is active in the range of tens of milligrams and the purity of any non-pharmaceutical preparation is uncertain, the dose actually received outside a clinical setting is difficult to know, a point of practical relevance when a clinician is assessing a patient's reported exposure.

{{ShulginsCorner

| quote = In a sense, DMT is to the world of indolic psychedelics what mescaline is to the world of phenethylamine psychedelics. It is the starting point of both our classification and understanding of the hallucinogenic psychedelics, and from it our entire understanding of the relationship between structure and activity must evolve.

| volume = TiHKAL

| page = p. 249

| voice = Commentary

}}

| interactions = <pharmaInteractions/>

| seealso = [[Ayahuasca]], [[LSD]]

| references = <references/>

}}

[[Category:~~Classic_Psychedelics~~]]

[[Category:Psychedelics]]

[[Category:Classical Psychedelics (Serotonergic)]]

[[Category:Tryptamines]]

[[Category:Plants]]

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