Dimethyltryptamine

{{Short description|Psychedelic drug}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Redirect|DMT}} {{About|N,N-dimethyltryptamine|other dimethyltryptamines|Dimethyltryptamine (disambiguation)}} {{Infobox drug | verifiedrevid = 623685269 | Watchedfields = changed | drug_name = Dimethyltryptamine | image = DMT.svg | image_class = skin-invert-image | width = 175px | image2 = Dimethyltryptamine molecule ball.png | image_class2 = bg-transparenT | width2 = 200px

| receptors = At least 13 receptors (e.g., serotonin, sigma, trace amine) | precursor = Tryptophan | source_tissues = Central nervous system (exact source tissues are not fully established) | target_tissues = Central nervous system

| routes_of_administration = Oral (with {{Abbrlink|MAOI|monoamine oxidase inhibitor}}), inhalation (smoking or vaping), intramuscular, subcutaneous, intravenous (bolus or infusion)<ref name="TiHKAL" /><ref name="CameronOlson2018" /><ref name="CarbonaroGatch2016" /><ref name="RodriguesAlmeidaVieira-Coelho2019" /><ref name="Brito-da-CostaDias-da-SilvaGomes2020" /> | class = Serotonin receptor agonist; Serotonin 5-HT2A receptor agonist; Serotonergic psychedelic; Hallucinogen | dependency_liability = None or very low | addiction_liability = None or very low | ATC_prefix = None

| legal_AU = S9 | legal_CA = Schedule III | legal_UK = Class A | legal_US = Schedule I | legal_DE = Anlage I | legal_BR = F2 | legal_BR_comment = <ref>{{cite web | author = Anvisa | date = 2023-07-24 | title = RDC Nº 804 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial | language = pt-BR | publisher = Diário Oficial da União | url = https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-804-de-24-de-julho-de-2023-498447451 | access-date = 2023-08-27 | archive-date = 2023-08-27 | archive-url = https://web.archive.org/web/20230827163149/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-804-de-24-de-julho-de-2023-498447451 | author-link = Brazilian Health Regulatory Agency | trans-title = Collegiate Board Resolution No. 804 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control | url-status = live | publication-date = 2023-07-25 }}</ref> | legal_UN = P I | legal_EU = Illegal | legal_status = SE: Illegal

| bioavailability = Very low and inactive (except with {{Abbrlink|MAOI|monoamine oxidase inhibitor}})<ref name="Brito-da-CostaDias-da-SilvaGomes2020" /> | protein_bound = | metabolism = Oxidative deamination ({{Abbrlink|MAO-A|Monoamine oxidase A}}), ''N''-oxidation, ''N''-demethylation, peroxidation<ref name="CameronOlson2018" /><ref name="CarbonaroGatch2016" /> | metabolites = * Indole-3-acetic acid (NMT) (63–97%)<ref name="CameronOlson2018" /><ref name="CarbonaroGatch2016" /><ref name="Brito-da-CostaDias-da-SilvaGomes2020" /> * DMT-''N''-oxide (DMT-NO) (3–28%)<ref name="CameronOlson2018" /><ref name="CarbonaroGatch2016" /><ref name="Brito-da-CostaDias-da-SilvaGomes2020" /> * ''N''-Methyltryptamine<ref name="CarbonaroGatch2016" /> * Tryptamine<ref name="CameronOlson2018" /> * Others<ref name="CameronOlson2018" /> | onset = * Inhalation: 10–15 seconds<ref name="Brito-da-CostaDias-da-SilvaGomes2020" /><ref name="CameronOlson2018" /><ref name="RodriguesAlmeidaVieira-Coelho2019" /> * Intravenous: ≤2–5 min<ref name="CameronOlson2018" /> * Intramuscular: 2–5{{nbsp}}min<ref name="CarbonaroGatch2016" /><ref name="RodriguesAlmeidaVieira-Coelho2019" /> * Oral with {{Abbrlink|MAOI|monoamine oxidase inhibitor}}: ≤1{{nbsp}}hour<ref name="CarbonaroGatch2016" /><ref name="RodriguesAlmeidaVieira-Coelho2019" /> | elimination_half-life = * Alone: 5–19{{nbsp}}min<ref name="GoodJoelBenway2023" /><ref name="vanderHeijdenOttoSchoones2025" /><ref name="CameronOlson2018" /><ref name="Brito-da-CostaDias-da-SilvaGomes2020" /><ref name="VollebregtStormLucassen2025">{{cite journal | vauthors = Vollebregt R, Storm AE, Lucassen PJ, Somers M | title = Psychedelic Experiences Elicited by Serotonergic Psychedelics; Molecular Mechanisms and Functional Connectivity Changes in /the Brain | journal = Neuroscience and Biobehavioral Reviews | volume = 181| issue = | article-number = 106529 | date = December 2025 | pmid = 41412413 | doi = 10.1016/j.neubiorev.2025.106529 | url = | doi-access = free | hdl = 11245.1/395e2646-cbd3-4836-8c23-2b300b0f1e75 | hdl-access = free }}</ref> * With {{Abbrlink|MAOI|monoamine oxidase inhibitor}}: 1–4{{nbsp}}hours<ref name="Brito-da-CostaDias-da-SilvaGomes2020" /><ref name="VollebregtStormLucassen2025" /> | duration_of_action = * Inhalation: ≤15{{nbsp}}min<ref name="CarbonaroGatch2016" /><ref name="RodriguesAlmeidaVieira-Coelho2019" /> * Intravenous: ≤30{{nbsp}}min<ref name="RodriguesAlmeidaVieira-Coelho2019" /><ref name="Barker2022">{{cite journal | vauthors = Barker SA | title = Administration of N,N-dimethyltryptamine (DMT) in psychedelic therapeutics and research and the study of endogenous DMT | journal = Psychopharmacology | volume = 239 | issue = 6 | pages = 1749–1763 | date = June 2022 | pmid = 35064294 | pmc = 8782705 | doi = 10.1007/s00213-022-06065-0 }}</ref> * Intramuscular: 30–60{{nbsp}}min<ref name="CarbonaroGatch2016" /><ref name="RodriguesAlmeidaVieira-Coelho2019" /> * Oral with {{Abbrlink|MAOI|monoamine oxidase inhibitor}}: 4–6{{nbsp}}hours<ref name="CarbonaroGatch2016" /><ref name="RodriguesAlmeidaVieira-Coelho2019" /><ref name="Brito-da-CostaDias-da-SilvaGomes2020" /><ref name="VollebregtStormLucassen2025" /> | excretion = Urine<ref name="Brito-da-CostaDias-da-SilvaGomes2020" />

| CAS_number_Ref = {{cascite|correct|??}} | CAS_number = 61-50-7 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DB01488 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = WUB601BHAA | ChEBI_Ref = {{ebicite|correct|EBI}} | ChEBI = 28969 | PubChem = 6089 | IUPHAR_ligand = 141 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 5864 | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = C08302 | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 12420 | PDB_ligand = A1AFV | synonyms = DMT; ''N'',''N''-dimethyltryptamine; ''N'',''N''-DMT; Desoxybufotenine; Desoxybufotenin; Nigerine; Dimitri; DiMiTri; "The Spirit Molecule"

| IUPAC_name = 2-(1''H''-indol-3-yl)-''N'',''N''-dimethylethanamine | C = 12 | H = 16 | N = 2 | SMILES = CN(CCC1=CNC2=C1C=CC=C2)C | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C12H16N2/c1-14(2)8-7-10-9-13-12-6-4-3-5-11(10)12/h3-6,9,13H,7-8H2,1-2H3 | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = DMULVCHRPCFFGV-UHFFFAOYSA-N

| density = 1.099 | melting_point = 40 | boiling_point = 160 | boiling_notes = at {{convert|0.6|Torr|Pa|abbr=on}}<ref>{{Cite journal |title=Untersuchungen zur Trifluoracetylierung der Methylderivate von Tryptamin und Serotonin mit verschiedenen Derivatisierungsreagentien: Synthesen, Spektroskopie sowie analytische Trennungen mittels Kapillar-GC |trans-title=Trifluoracetylation of methylated derivatives of tryptamine and serotonin by different reagents: synthesis, spectroscopic characterizations, and separations by capillary gas chromatography |year=1999 |journal=Zeitschrift für Naturforschung B |volume=54 |issue=3 |pages=397–414 | vauthors = Häfelinger G, Nimtz M, Horstmann V, Benz T |doi=10.1515/znb-1999-0319 |s2cid=101000504 }}</ref> also reported as {{convert|80|-|135|C}} at {{convert|0.03|Torr|Pa|abbr=on}}<ref>{{cite journal | vauthors = Corothie E, Nakano T | title = Constituents of the bark of Virola sebifera | journal = Planta Medica | volume = 17 | issue = 2 | pages = 184–188 | date = May 1969 | pmid = 5792479 | doi = 10.1055/s-0028-1099844 | bibcode = 1969PlMed..17..184C | s2cid = 43312376 }}</ref> }}

'''Dimethyltryptamine''' ('''DMT'''), also known as '''''N'',''N''-dimethyltryptamine''' ('''''N'',''N''-DMT'''), is a serotonergic hallucinogen and investigational drug of the tryptamine family that occurs naturally in many plants and animals.<ref name="CameronOlson2018">{{cite journal | vauthors = Cameron LP, Olson DE | title = Dark Classics in Chemical Neuroscience: N, N-Dimethyltryptamine (DMT) | journal = ACS Chemical Neuroscience | volume = 9 | issue = 10 | pages = 2344–2357 | date = October 2018 | pmid = 30036036 | doi = 10.1021/acschemneuro.8b00101 }}</ref><ref name="CarbonaroGatch2016">{{cite journal | vauthors = Carbonaro TM, Gatch MB | title = Neuropharmacology of ''N'',''N''-dimethyltryptamine | journal = Brain Research Bulletin | volume = 126 | issue = Pt 1 | pages = 74–88 | date = September 2016 | pmid = 27126737 | pmc = 5048497 | doi = 10.1016/j.brainresbull.2016.04.016 }}</ref><ref name="RodriguesAlmeidaVieira-Coelho2019">{{cite journal | vauthors = Rodrigues AV, Almeida FJ, Vieira-Coelho MA | title = Dimethyltryptamine: Endogenous Role and Therapeutic Potential | journal = Journal of Psychoactive Drugs | volume = 51 | issue = 4 | pages = 299–310 | date = 2019 | pmid = 31018803 | doi = 10.1080/02791072.2019.1602291 | hdl = 10216/114373 | url = | hdl-access = free }}</ref><ref name="TiHKAL">{{cite web|url=https://www.erowid.org/library/books_online/tihkal/tihkal06.shtml|title=Erowid Online Books: "TIHKAL" – #6 DMT|website=Erowid.org|access-date=2015-09-10|archive-date=2015-09-16|archive-url=https://web.archive.org/web/20150916005755/https://www.erowid.org/library/books_online/tihkal/tihkal06.shtml|url-status=live}}</ref> DMT is used as a psychedelic drug and prepared by various cultures for ritual purposes as an entheogen.<ref name="McKennaTowers1984a">{{cite journal | vauthors = McKenna DJ, Towers GH, Abbott F | title = Monoamine oxidase inhibitors in South American hallucinogenic plants: tryptamine and beta-carboline constituents of ayahuasca | journal = Journal of Ethnopharmacology | volume = 10 | issue = 2 | pages = 195–223 | date = April 1984 | pmid = 6587171 | doi = 10.1016/0378-8741(84)90003-5 | bibcode = 1984JEthn..10..195M }}</ref>

DMT has a rapid onset, intense effects, and a relatively short duration of action. For those reasons, DMT was known as the "businessman's trip" during the 1960s in the United States, as a user could access the full depth of a psychedelic experience in considerably less time than with other substances such as LSD or psilocybin mushrooms.<ref name="HarozGreenberg2005">{{cite journal | vauthors = Haroz R, Greenberg MI | title = Emerging drugs of abuse | journal = The Medical Clinics of North America | volume = 89 | issue = 6 | pages = 1259–1276 | date = November 2005 | pmid = 16227062 | doi = 10.1016/j.mcna.2005.06.008 | oclc = 610327022 }}</ref> DMT can be inhaled or injected and its effects depend on the dose, as well as the mode of administration. When inhaled or injected, the effects last about five to fifteen 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.<ref name="Pickover 2005">{{cite book | vauthors = Pickover C | year = 2005 | title = Sex, Drugs, Einstein, and Elves: Sushi, Psychedelics, Parallel Universes, and the Quest for Transcendence | publisher = Smart Publications | isbn = 978-1-890572-17-4 | url = https://archive.org/details/sexdrugseinstein00clif }}</ref> DMT induces intense, often indescribable subjective experiences involving vivid visual hallucinations, altered sensory perception, ego dissolution, and encounters with seemingly autonomous entities. DMT is generally considered non-addictive with low dependence and no tolerance buildup, but it may cause acute psychological distress or cardiovascular effects, especially in predisposed individuals.

DMT was first synthesized in 1931. It is a functional and structural analog of other psychedelic tryptamines such as 4-AcO-DMT (''O''-acetylpsilocin),<ref>{{cite journal | vauthors = Jones NT, Wagner L, Hahn MC, Scarlett CO, Wenthur CJ | title = ''In vivo'' validation of psilacetin as a prodrug yielding modestly lower peripheral psilocin exposure than psilocybin | language = English | journal = Frontiers in Psychiatry | volume = 14 | article-number = 1303365 | date = 2024-01-08 | pmid = 38264637 | doi = 10.3389/fpsyt.2023.1303365 | doi-access = free | pmc = 10804612 }}</ref> psilocybin (4-PO-DMT), psilocin (4-HO-DMT), ''O''-methylbufotenin (5-MeO-DMT), and bufotenin (5-HO-DMT). Parts of the structure of DMT occur within some important biomolecules like serotonin and melatonin, making them structural analogues of DMT.

DMT exhibits broad and variable binding affinities across numerous receptors, showing its strongest interactions with serotonin receptors, especially 5-HT2A, 5-HT1A, and 5-HT2C, which are believed to mediate its psychedelic effects. Endogenous DMT, a psychedelic compound, is naturally produced in mammals, with evidence showing its synthesis and presence in brain and body tissues, though its exact roles and origins remain debated. DMT is internationally illegal without authorization, with most countries banning its possession and trade, though some allow religious use of ayahuasca, a DMT-containing decoction. Short-acting psychedelics like DMT are considered scalable alternatives to longer-acting drugs like psilocybin for potential clinical use.<ref name="Ramaekers2025"/><ref name="RamaekersReckwegMason2025"/> DMT is currently undergoing clinical trials for treatment-resistant depression.<ref name="LucidoDunlop2025">{{cite journal | vauthors = Lucido MJ, Dunlop BW | title = Emerging Medications for Treatment-Resistant Depression: A Review with Perspective on Mechanisms and Challenges | journal = Brain Sciences | volume = 15 | issue = 2 | date = February 2025 | page = 161 | pmid = 40002494 | pmc = 11853532 | doi = 10.3390/brainsci15020161 | doi-access = free }}</ref>

==Use and effects== {{See also|Ayahuasca|Pharmahuasca|Changa (drug)}}

===Forms, routes, and doses=== [[File:Aya-preparation.jpg|thumb|left|200px|Ayahuasca preparation.]]

DMT is used either in pure form or in the form of naturally sourced materials.<ref name="CameronOlson2018" /><ref name="TiHKAL" /> It occurs naturally in many plants, among the more notable species including ''Psychotria viridis'', ''Mimosa tenuiflora'', and ''Diplopterys cabrerana''.<ref name="DosSantosHallak2024" /><ref name="CameronOlson2018" /><ref name="TorresRepke2006" /> The drug is often present alongside its close analogues 5-MeO-DMT (mebufotenin) and bufotenin (5-HO-DMT).<ref name="TorresRepke2006" /> It has widely been used as an entheogen or for shamanistic purposes in Central and South America, for instance among Amazonian peoples.<ref name="CameronOlson2018" /> This includes as the traditional beverage ayahuasca and other forms.<ref name="CameronOlson2018" /> Ayahuasca is boiled mixture of different plants, including a DMT-containing plant like ''Psychotria viridis'', ''Psychotria carthagenensis'', or ''Diplopterys cabrerana'' together with another plant known as ''Banisteriopsis caapi''.<ref name="CameronOlson2018" /><ref name="McKennaTowers1984b" /> A variety of different recipes may be used to make the brew.<ref name="Andritzky1989">{{cite journal | vauthors = Andritzky W | title = Sociopsychotherapeutic functions of ayahuasca healing in Amazonia | journal = Journal of Psychoactive Drugs | volume = 21 | issue = 1 | pages = 77–89 | year = 1989 | pmid = 2656954 | doi = 10.1080/02791072.1989.10472145 | url = http://www.lila.info/document_view.phtml?document_id=8 | archive-url = https://web.archive.org/web/20080226052014/http://www.lila.info/document_view.phtml?document_id=8 | archive-date = 26 February 2008 }}</ref> DMT is usually the main active constituent of ayahuasca, but ayahuasca is sometimes also brewed with plants that do not contain DMT.<ref name="RivierLindgren1972">{{cite journal | vauthors = Rivier L, Lindgren JE |title='Ayahuasca,' the South American hallucinogenic drink: An ethnobotanical and chemical investigation |journal=Economic Botany |volume=26 |issue=2 |year=1972 |pages=101–129 |issn=0013-0001 |doi=10.1007/BF02860772 |bibcode=1972EcBot..26..101R |s2cid=34669901}}</ref><ref name="McKennaTowers1984b"/> The drug is also found as a minor alkaloid in hallucinogenic snuffs such as those made from ''Virola'' or ''Anadenanthera'' plant materials but in which the major active drugs are instead 5-MeO-DMT and/or bufotenin.<ref name="TorresRepke2006">{{cite book | vauthors = Torres CM, Repke DB | year = 2006 | title = Anadenanthera: Visionary Plant Of Ancient South America | publisher = Haworth Herbal | pages = [https://archive.org/details/anadenantheravis00torr_088/page/n126 107]–122 | isbn = 978-0-7890-2642-2 | url = https://archive.org/details/anadenantheravis00torr_088 | url-access = limited | location = Binghamton, NY }}</ref><ref name="Ott2001">{{cite journal | vauthors = Ott J | title = Pharmañopo-psychonautics: human intranasal, sublingual, intrarectal, pulmonary and oral pharmacology of bufotenine | journal = Journal of Psychoactive Drugs | volume = 33 | issue = 3 | pages = 273–281 | year = 2001 | pmid = 11718320 | doi = 10.1080/02791072.2001.10400574 | s2cid = 5877023 | url = http://files.shroomery.org/attachments/8588382-pharmanopo_J_Ott_2001_J_Psych_Drug.pdf | access-date = 2010-11-16 | archive-date = 2011-07-26 | archive-url = https://web.archive.org/web/20110726003945/http://files.shroomery.org/attachments/8588382-pharmanopo_J_Ott_2001_J_Psych_Drug.pdf | url-status = live }}</ref> In addition to its use as an entheogen, DMT is used recreationally.<ref name="CameronOlson2018" /><ref name="CarbonaroGatch2016" />

DMT is not orally active on its own and is given by parenteral administration, such as smoking, intramuscular injection, subcutaneous injection, or intravenous injection.<ref name="CameronOlson2018" /><ref name="CarbonaroGatch2016" /><ref name="TiHKAL" /><ref name="McKennaTowers1984b" /> Other routes like intranasal, buccal, or rectal administration have also been tried but were all reported to be inactive.<ref name="CarbonaroGatch2016" /><ref name="TiHKAL" /> The lack of oral activity of DMT is due to rapid metabolism by the enzyme monoamine oxidase A (MAO-A).<ref name="CameronOlson2018" /><ref name="McKennaTowers1984b" /> However, when taken in combination with an irreversible monoamine oxidase inhibitor (MAOI) or a reversible inhibitor of MAO-A (RIMA) such as a harmala alkaloid like harmine or harmaline or a pharmaceutical RIMA like moclobemide, DMT becomes orally active with an extended duration relative to parenteral use of DMT alone.<ref name="CameronOlson2018" /><ref name="EggerAicherCumming2024">{{cite journal | vauthors = Egger K, Aicher HD, Cumming P, Scheidegger M | date = September 2024 | title = Neurobiological research on N,N-dimethyltryptamine (DMT) and its potentiation by monoamine oxidase (MAO) inhibition: from ayahuasca to synthetic combinations of DMT and MAO inhibitors | journal = Cellular and Molecular Life Sciences | volume = 81 | issue = 1 | page = 395 | doi = 10.1007/s00018-024-05353-6 | pmc = 11387584 | pmid = 39254764 }}</ref><ref name="Barker2022" /><ref name="McKennaTowers1984b" /> Certain plants like ''Peganum harmala'' and the ''Banisteriopsis caapi'' used in ayahuasca contain harmala alkaloids which allow DMT to become orally active.<ref name="CameronOlson2018" /> When oral DMT is used with an MAOI and the materials are not naturally sourced, the combination is known as pharmahuasca.<ref name="EggerAicherCumming2024" /> Changa is a plant-derived form of DMT that is smoked.<ref name="JamesKepplerRobertshaw2022">{{cite journal | vauthors = James E, Keppler J, L Robertshaw T, Sessa B | title = N,N-dimethyltryptamine and Amazonian ayahuasca plant medicine | journal = Human Psychopharmacology | volume = 37 | issue = 3 | article-number = e2835 | date = May 2022 | pmid = 35175662 | pmc = 9286861 | doi = 10.1002/hup.2835 }}</ref> Smoking and intravenous injection of DMT have extremely intense but very-short-lived effects, whereas intramuscular injection and particularly oral administration with an MAOI have less intense but longer-lasting effects.<ref name="CarbonaroGatch2016" /><ref name="TiHKAL" />

[[File:N,N-DMT Freebase and Vape cartridge.jpg|thumb|left|200px|Free-base DMT powder extracted from ''Mimosa hostilis'' root bark (left); vape cartridge made with free-base DMT extract (right).]]

In his book ''TiHKAL'' (''Tryptamines I Have Known and Loved'') and other publications, Alexander Shulgin lists DMT's dose as greater than 350{{nbsp}}mg orally, 60 to 100{{nbsp}}mg by intramuscularly, subcutaneously, or via smoking, and 4 to 30{{nbsp}}mg by intravenous injection.<ref name="TiHKAL" /><ref name="CarbonaroGatch2016" /> He also reported that doses of 150 to 350{{nbsp}}mg or even up to 1,000{{nbsp}}mg orally and a dose of 100{{nbsp}}mg buccally produced no effects, whereas doses of 20 to 80{{nbsp}}mg intramuscularly, 30 to 100{{nbsp}}mg smoked, and 15 to 30{{nbsp}}mg intravenously were all active in producing effects.<ref name="TiHKAL" /><ref name="Shulgin1976" /><ref name="DosSantosHallak2024" /><ref name="McKennaTowers1984b">{{cite journal | vauthors = McKenna DJ, Towers GH | title = Biochemistry and pharmacology of tryptamines and beta-carbolines. A minireview | journal = Journal of Psychoactive Drugs | volume = 16 | issue = 4 | pages = 347–358 | date = 1984 | pmid = 6394730 | doi = 10.1080/02791072.1984.10472305 | url = https://bitnest.netfirms.com/external/10.1080/02791072.1984.10472305| url-access = subscription | quote = [...] all are apparently orally active except for DMT itself, which is orally inactive in doses exceeding 1,000 mg.}}</ref> In terms of intramuscular injection, threshold effects occur at a dose of 30{{nbsp}}mg and full effects occur at a dose of 50 to 100{{nbsp}}mg by this route.<ref name="Shulgin1976">{{cite journal | vauthors = Shulgin AT | title=Profiles of Psychedelic Drugs: DMT & TMA-2 | journal=Journal of Psychedelic Drugs | volume=8 | issue=2 | date=1976 | issn=0022-393X | doi=10.1080/02791072.1976.10471846 | pages=167–169 | url=https://www.tandfonline.com/doi/full/10.1080/02791072.1976.10471846 | access-date=8 April 2025| url-access=subscription }}</ref><ref name="TiHKAL" /> Similarly, the dose for full effects with subcutaneous injection is likewise 60 to 100{{nbsp}}mg.<ref name="Shulgin1976" /> With regard to intravenous injection, a dose of 4{{nbsp}}mg was indistinguishable from placebo, 8{{nbsp}}mg produced physical effects but no psychoactive effects, 15{{nbsp}}mg produced threshold psychedelic effects, and 30{{nbsp}}mg produced strong psychedelic effects.<ref name="TiHKAL" /> Shulgin lists the duration of parenteral DMT alone as up to 1{{nbsp}}hour.<ref name="TiHKAL" />

In other more recent publications, different dose ranges of inhaled DMT of 2 to 100{{nbsp}}mg or 15 to 60{{nbsp}}mg have been described<ref name="LuethiLiechti2018">{{cite journal | vauthors = Luethi D, Liechti ME | title = Monoamine Transporter and Receptor Interaction Profiles in Vitro Predict Reported Human Doses of Novel Psychoactive Stimulants and Psychedelics | journal = The International Journal of Neuropsychopharmacology | volume = 21 | issue = 10 | pages = 926–931 | date = October 2018 | pmid = 29850881 | pmc = 6165951 | doi = 10.1093/ijnp/pyy047 }}</ref><ref name="BallentineFriedmanBzdok2022">{{cite journal | vauthors = Ballentine G, Friedman SF, Bzdok D | title = Trips and neurotransmitters: Discovering principled patterns across 6850 hallucinogenic experiences | journal = Science Advances | volume = 8 | issue = 11 | article-number = eabl6989 | date = March 2022 | pmid = 35294242 | pmc = 8926331 | doi = 10.1126/sciadv.abl6989 | bibcode = 2022SciA....8L6989B }}</ref> and typical doses have been reported to be 40 to 50{{nbsp}}mg.<ref name="Barker2022" /> Concerning intravenous injection and based on contemporary clinical studies, 15{{nbsp}}mg has been described as a low dose, 25{{nbsp}}mg as an intermediate or "good effect" dose, and 30{{nbsp}}mg as a high or "ego-dissolution" dose.<ref name="LiechtiHolze2022" /> For intramuscular injection, a range of 50 to 100{{nbsp}}mg with an estimated typical dose of 75{{nbsp}}mg has been noted.<ref name="HalberstadtChathaKlein2020" /> The onset of DMT has been given as 10 to 15{{nbsp}}seconds smoked,<ref name="Brito-da-CostaDias-da-SilvaGomes2020" /><ref name="CameronOlson2018" /><ref name="RodriguesAlmeidaVieira-Coelho2019" /> within 2 to 5{{nbsp}}minutes intravenously,<ref name="CameronOlson2018" /> and within 2 to 5{{nbsp}}minutes intramuscularly.<ref name="CarbonaroGatch2016" /><ref name="RodriguesAlmeidaVieira-Coelho2019" /> In addition, its duration is given as 5 to 20{{nbsp}}minutes (average 12{{nbsp}}minutes) via inhalation,<ref name="CarbonaroGatch2016" /><ref name="RodriguesAlmeidaVieira-Coelho2019" /><ref name="BallentineFriedmanBzdok2022" /> less than 30{{nbsp}}minutes intravenously,<ref name="RodriguesAlmeidaVieira-Coelho2019" /><ref name="Barker2022" /> and 30 to 60{{nbsp}}minutes intramuscularly.<ref name="CarbonaroGatch2016" /><ref name="RodriguesAlmeidaVieira-Coelho2019" />

DMT by continuous intravenous infusion (i.e., an intravenous "drip", also sometimes known as "DMTx") has additionally been developed recently and can extend the duration of intravenous DMT to hours.<ref name="LiechtiHolze2022">{{cite book | vauthors = Liechti ME, Holze F | date = 2022 | chapter = Dosing Psychedelics and MDMA | title = Disruptive Psychopharmacology | volume = 56 | pages = 3–21 | isbn = 978-3-031-12183-8 | doi = 10.1007/7854_2021_270 | pmid = 34734392 | series = Curr Top Behav Neurosci | chapter-url = https://www.researchgate.net/publication/355943062 }}</ref><ref name="HolzeSinghLiechti2024">{{cite journal | vauthors = Holze F, Singh N, Liechti ME, D'Souza DC | title = Serotonergic Psychedelics: A Comparative Review of Efficacy, Safety, Pharmacokinetics, and Binding Profile | journal = Biological Psychiatry. Cognitive Neuroscience and Neuroimaging | volume = 9 | issue = 5 | pages = 472–489 | date = May 2024 | pmid = 38301886 | doi = 10.1016/j.bpsc.2024.01.007 | url = | doi-access = free }}</ref><ref name="VogtLeyErne2023" /><ref name="LuanEckernäsAshton2024" /><ref name="ErneVogtMüller2025" /> The dose range for this route is 0.6 to 1.8{{nbsp}}mg per minute, with 0.6{{nbsp}}mg/minute being a low dose, 1.2{{nbsp}}mg/minute being an intermediate or "good effect" dose, and 1.8 to 2.4{{nbsp}}mg/minute being a high or "ego dissolution" dose.<ref name="LiechtiHolze2022" /><ref name="HolzeSinghLiechti2024" /> In addition to continuous intravenous infusion, DMT vape pens have been developed and distributed as an alternative to smoking.<ref name="Power2020">{{cite web | vauthors = Power M | date = 5 June 2020 | title = I Sell DMT Vape Pens So People Can 'Break Through' at Their Own Speed | website = Vice.com | url = https://www.vice.com/en/article/i-sell-dmt-vape-pens-so-people-can-break-through-at-their-own-speed/ | access-date = 12 July 2020 | archive-date = 12 July 2020 | archive-url = https://web.archive.org/web/20200712192852/https://www.vice.com/en_uk/article/akzgbz/i-sell-dmt-vape-pens-so-people-can-break-through-at-their-own-speed | url-status = live }}</ref><ref name="Black2018" /><ref name="McClure2020" />

Besides parenteral DMT alone, Shulgin also described the properties of oral DMT in combination with the MAOI and distinct ibogaine-like hallucinogen harmaline or in some cases ''Peganum harmala'' seeds in ''TiHKAL''.<ref name="TiHKAL-Harmaline">{{cite web | title=Erowid Online Books: "TIHKAL" - #13 HARMALINE | website=www.erowid.org | url=http://www.erowid.org/library/books_online/tihkal/tihkal13.shtml | access-date=11 April 2025}}</ref> This combination is a form of pharmahuasca and is similar to ayahuasca.<ref name="TiHKAL-Harmaline" /> Doses of 20 to 50{{nbsp}}mg harmaline with 55 to 60{{nbsp}}mg DMT both orally were associated with few to no effects.<ref name="TiHKAL-Harmaline" /> At higher harmaline doses, including 80 to 150{{nbsp}}mg, combined with 35 to 120{{nbsp}}mg DMT, both orally, clear MAOI activity occurred and more significant effects became apparent.<ref name="TiHKAL-Harmaline" /> More recent publications have defined the usually recommended doses as 50{{nbsp}}mg DMT and 100{{nbsp}}mg harmaline orally.<ref name="Barker2022" /> Besides DMT with harmaline, the properties and effects of oral DMT in combination with harmine have also been studied by Jonathan Ott.<ref name="Ott1998">{{cite book | vauthors = Ott J | year = 1998 | veditors = Müller-Ebeling C | chapter = Pharmahuasca, anahuasca and vinho da jurema: human pharmacology of oral DMT plus harmine | title = Special: Psychoactivity | publisher = VWB | volume = 6/7 (1997/1998) | isbn = 978-3-86135-033-0 | access-date = 2010-11-29 | archive-date = 2018-10-31 | archive-url = https://web.archive.org/web/20181031212537/https://www.erowid.org/references/texts/show/7105docid6446 | author-link1 = Jonathan Ott | series = Yearbook for Ethnomedicine and the Study of Consciousness | location = Berlin | chapter-url = https://www.erowid.org/references/texts/show/7105docid6446 }}</ref><ref name="Ott1999">{{cite journal | vauthors = Ott J | title = Pharmahuasca: human pharmacology of oral DMT plus harmine | journal = Journal of Psychoactive Drugs | volume = 31 | issue = 2 | pages = 171–177 | date = 1999 | pmid = 10438001 | doi = 10.1080/02791072.1999.10471741 }}</ref> He found that the threshold dose was 20 or 30{{nbsp}}mg DMT and 120{{nbsp}}mg harmine orally.<ref name="Ott1998" /><ref name="Ott1999" /> Shulgin also reported in ''TiHKAL'' that 35 to 40{{nbsp}}mg DMT and 140 to 190{{nbsp}}mg harmine were unmistakably active, whereas smaller doses of 30{{nbsp}}mg DMT and 120 to 140{{nbsp}}mg harmine orally were inactive.<ref name="TiHKAL-Harmine">{{CiteTiHKAL}} https://erowid.org/library/books_online/tihkal/tihkal14.shtml</ref> In notable contrast to harmaline, harmine does not have its own psychoactive effects when used at doses of up to at least 300{{nbsp}}mg orally.<ref name="TiHKAL-Harmine" /><ref name="AblesIsraelWood2024">{{cite journal | vauthors = Ables JL, Israel L, Wood O, Govindarajulu U, Fremont RT, Banerjee R, Liu H, Cohen J, Wang P, Kumar K, Lu G, DeVita RJ, Garcia-Ocaña A, Murrough JW, Stewart AF | title = A Phase 1 single ascending dose study of pure oral harmine in healthy volunteers | journal = Journal of Psychopharmacology | volume = 38 | issue = 10 | pages = 911–923 | date = October 2024 | pmid = 39301926 | pmc = 11549898 | doi = 10.1177/02698811241273772 }}</ref> In pharmahuasca, the harmala alkaloid is usually taken first and then DMT is taken 15 to 20{{nbsp}}minutes later, although a shorter or longer interval may also be employed.<ref name="Barker2022" /><ref name="TiHKAL-Harmine" /> The onset of oral DMT with an MAOI is within 1{{nbsp}}hour<ref name="CarbonaroGatch2016" /><ref name="RodriguesAlmeidaVieira-Coelho2019" /> and its duration is 4 to 6{{nbsp}}hours.<ref name="CarbonaroGatch2016" /><ref name="RodriguesAlmeidaVieira-Coelho2019" /><ref name="Brito-da-CostaDias-da-SilvaGomes2020" /><ref name="EggerAicherCumming2024" />

===Subjective effects=== Subjective experiences of DMT indubitably includes profound time-dilatory, visual, auditory, tactile, and proprioceptive distortions and hallucinations, and other experiences that, by most firsthand accounts, defy verbal or visual description.<ref name="pmid8297217">{{cite journal | vauthors = Strassman RJ, Qualls CR, Uhlenhuth EH, Kellner R | title = Dose-response study of ''N'',''N''-dimethyltryptamine in humans. II. Subjective effects and preliminary results of a new rating scale | journal = Archives of General Psychiatry | url = https://jamanetwork.com/journals/jamapsychiatry/article-abstract/496497 | volume = 51 | issue = 2 | pages = 98–108 | date = February 1994 | pmid = 8297217 | doi = 10.1001/archpsyc.1994.03950020022002 | access-date = 2023-05-05 | archive-date = 2023-05-05 | archive-url = https://web.archive.org/web/20230505025912/https://jamanetwork.com/journals/jamapsychiatry/article-abstract/496497 | url-status = live | url-access = subscription }}</ref> Examples include perceiving hyperbolic geometry or seeing Escher-like impossible objects.<ref name="Hyperbolic Geometry of DMT Experiences">{{cite speech | vauthors = Gómez Emilsson A |title=The Hyperbolic Geometry of DMT Experiences |event=Harvard Science of Psychedelics Club |date=5 October 2019 |location=Harvard University, Cambridge, Massachusetts |publisher=Qualia Research Institute |url=https://www.youtube.com/watch?v=loCBvaj4eSg | archive-url=https://ghostarchive.org/varchive/youtube/20211211/loCBvaj4eSg| archive-date=2021-12-11 | url-status=live|access-date=27 April 2020 |language=en}}{{cbignore}}</ref>

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

Rick Strassman and his colleagues conducted a five-year-long DMT study at the University of New Mexico in the 1990s.<ref name="pmid8297216">{{cite journal | vauthors = Strassman RJ, Qualls CR | title = Dose-response study of ''N'',''N''-dimethyltryptamine in humans. I. Neuroendocrine, autonomic, and cardiovascular effects | journal = Archives of General Psychiatry | volume = 51 | issue = 2 | pages = 85–97 | date = February 1994 | pmid = 8297216 | doi = 10.1001/archpsyc.1994.03950020009001 }}</ref> The results provided insight about the quality of subjective psychedelic experiences. In this study participants received the DMT dose via intravenous injection and the findings suggested that different psychedelic experiences can occur, depending on the dose. 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).<ref name="pmid8297216" /> 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 experiences of euphoria, calm, fear, and anxiety.<ref name="pmid8297216" /> These dose-dependent effects match well with anonymously posted "trip reports" online, where users report "breakthroughs" above certain doses.<ref>{{cite journal | vauthors = St John G | date = 2018 | title = The Breakthrough Experience: DMT Hyperspace and its Liminal Aesthetics | journal = Anthropology of Consciousness | volume = 29 | issue = 1 | pages = 57–76 | doi = 10.1111/anoc.12089 | issn = 1556-3537 }}</ref>{{Additional citation needed|date=November 2025}}

Strassman also highlighted 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.<ref name="Strassman2001" /><ref name="pmid8297216" />

It appears that DMT can induce a state or feeling wherein the person believes they "communicate with other intelligent lifeforms" (see "Entity encounters" below). High doses of DMT produce a state that involves a sense of "another intelligence" that people sometimes describe as "super-intelligent", but "emotionally detached".<ref name="pmid8297216" />

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.<ref name="Dittrich">{{cite journal| vauthors = Lamparter D, Dittrich A |title=Intraindividuelle Stabilität von ABZ unter sensorischer Deprivation, ''N'',''N''-Dimethyltryptamin (DMT) und Stickoxydul | trans-title = Intra-individual stability of ABZ under sensory deprivation, ''N'',''N''-dimethyltryptamine (DMT) and nitric oxide |journal= Jahrbuch des Europäischen Collegiums für Bewusstseinsstudien | trans-journal = Yearbook of the European College for the Study of Consciousness | language = de |date=1995|pages=33–44}}</ref> 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.<ref>{{cite journal | vauthors = Vollenweider FX | title = Brain mechanisms of hallucinogens and entactogens | journal = Dialogues in Clinical Neuroscience | volume = 3 | issue = 4 | pages = 265–279 | date = December 2001 | doi = 10.31887/DCNS.2001.3.4/fxvollenweider | pmid = 22033605 | pmc = 3181663 }}</ref> 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.<ref name="Dittrich" />

The effects of parenterally administered DMT have been described by Alexander Shulgin in his book ''TiHKAL'' (''Tryptamines I Have Known and Loved'').<ref name="TiHKAL" /> The perceptual effects included feeling strange, closed-eye imagery such as beautiful colored kaleidoscopic images, fast-moving geometric patterns, and complex and wonderful scenes alternating very rapidly, open-eye psychedelic visuals such as moving patterns, patterns becoming heads of animals, and people's faces seeming to be masks, perceptual disturbances and distortions, yellowing of visual field, and rare auditory changes.<ref name="TiHKAL" /> Other effects included feeling intoxicated or stoned, everything feeling blurry, feeling a rush, time dilation, loss of spatial perception, ego dissolution, feeling as if one has died or no longer exists, feeling like one has no body, feeling that one is moving at the speed of light, feeling like one is gazing upon the entire universe, and encounters with strange entities or creatures.<ref name="TiHKAL" /> Emotional effects included emotional changes, euphoria, imagery being associated with deep emotional content and connotation, feeling overwhelmed, anxiety and fear, feeling like one can't breathe, a sense of dread and doom, and wanting one's mother.<ref name="TiHKAL" /> Physical side effects included pupil dilation, tingling, trembling, numbness, sweating, lightheadedness, athetosis, slight nausea, and increased heart rate and blood pressure.<ref name="TiHKAL" />

In addition to parenteral DMT, Shulgin described the effects of oral DMT plus harmaline or in some cases ''Peganum harmala'' seeds in ''TiHKAL''.<ref name="TiHKAL-Harmaline" /> The effects were reported to include closed-eye imagery such as colors, infinitely repeated and wavy sheets of patterns, and kaleidoscopic images, visual changes like brighter colors and patterns and distortions, music enhancement, time distortion, clarity, insights, intoxication, emotional changes, feeling alive and excited, depression, despair, and feeling psychotic.<ref name="TiHKAL-Harmaline" /> Other effects included difficulty focusing on thoughts, short-term memory disruption, feeling cold, nausea, gait impairment or difficulty walking, and an afterglow.<ref name="TiHKAL-Harmaline" /> The preceding effects are variably due to both DMT and harmaline, with harmaline also producing its own hallucinogenic effects at sufficiently doses, for instance 150{{nbsp}}mg or more.<ref name="TiHKAL-Harmaline" />

{{Anchor|Entity encounters}} ====Entity encounters==== Entities perceived during DMT inebriation have been represented in diverse forms of psychedelic art. The term ''machine elf'' was coined by ethnobotanist Terence McKenna for the entities he encountered in DMT "hyperspace", along with terms like ''fractal elves'', or ''self-transforming machine elves''.<ref>{{harvnb|Strassman|2001|pages=[https://archive.org/details/dmtspiritmolecul00rick/page/187 187–188, also pp.173–174]}} "I had expected to hear about some of these types of experiences once we began giving DMT. I was familiar with Terence McKenna's tales of the "self-transforming machine elves" he encountered after smoking high doses of the drug. Interviews conducted with twenty experienced DMT smokers before beginning the New Mexico research also yielded some tales of similar meetings with such entities. Since most of these people were from California, I admittedly chalked up these stories to some kind of West Coast eccentricity"</ref><ref>{{cite book | vauthors = Oeric ON, McKenna T | year = 1975 | title = The Invisible Landscape: Mind, Hallucinogens and the I Ching | publisher = Seabury Press | isbn = 978-0-8164-9249-7 }}</ref> 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.<ref>{{cite book | vauthors = St John G | date = 2015 | chapter = Chapters 4, 6, and 12 | title = Mystery School in Hyperspace: A Cultural History of DMT | publisher = North Atlantic Books / Evolver Editions | isbn = 978-1-58394-732-6 | location = Berkeley, California }}</ref> Cliff Pickover has also written about the "machine elf" experience, in the book ''Sex, Drugs, Einstein, & Elves''.<ref name="Pickover 2005" /> 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.<ref name="Prophecy 2014">{{cite book | vauthors = Strassman R | date = 2014 | title = DMT and the Soul of Prophecy: A New Science of Spiritual Revelation in the Hebrew Bible | publisher = Simon and Schuster | isbn = 978-1-62055-168-4 }}</ref> Strassman also argues for a similarity in his study participants' descriptions of mechanized wheels, gears and machinery in these encounters, with those described in visions of encounters with the Living Creatures and Ophanim of the Hebrew Bible, noting they may stem from a common neuropsychopharmacological experience.<ref name="Prophecy 2014"/>

Strassman argues that the more positive of the "external entities" encountered in DMT experiences should be understood as analogous to certain forms of angels: {{blockquote|The medieval Jewish philosophers whom I rely upon for understanding the Hebrew Bible text and its concept of prophecy portray angels as God's intermediaries. That is, they perform a certain function for God. Within the context of my DMT research, I believe that the beings that volunteers see could be conceived of as angelic – that is, previously invisible, incorporeal spiritual forces that are engarbed or enclothed in a particular form – determined by the psychological and spiritual development of the volunteers – bringing a particular message or experience to that volunteer.<ref>{{cite web | vauthors = Solomon A | date = 3 May 2011 | title = Interview: Dr. Rick Strassman | website = Boing Boing | url = https://boingboing.net/2011/05/03/strassman.html | access-date = 11 November 2018 | archive-date = 26 May 2024 | archive-url = https://web.archive.org/web/20240526041615/https://boingboing.net/2011/05/03/strassman.html | url-status = live }}</ref>}} Strassman's experimental participants also note that some other entities can subjectively resemble creatures more like insects and aliens.{{sfn|Strassman|2001|pages=[https://archive.org/details/dmtspiritmolecul00rick/page/206 206–208]}} 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."{{sfn|Strassman|2001|pages=[https://archive.org/details/dmtspiritmolecul00rick/page/202 202]}}

Hallucinations of strange creatures had been reported by Stephen Szára 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.<ref>{{cite web | vauthors = Hanks MA | date = 10 September 2010 | title = Causal Multiplicity: The Science Behind Schizophrenia | website = Red Ice | url = http://www.redicecreations.com/article.php?id=12496 | access-date = 18 November 2014 | archive-date = 29 November 2014 | archive-url = https://web.archive.org/web/20141129020944/http://www.redicecreations.com/article.php?id=12496 | url-status = live }}</ref><ref>{{cite web|url=http://www.buildingalienworlds.com/uploads/5/7/9/9/57999785/dmt_research_1956_edge_time_arg_dpl_final.pdf |archive-url=https://web.archive.org/web/20160324035110/http://www.buildingalienworlds.com/uploads/5/7/9/9/57999785/dmt_research_1956_edge_time_arg_dpl_final.pdf |archive-date=2016-03-24 |url-status=live |title=DMT research from 1956 to the edge of time |date=15 December 2015 | vauthors = Gallimore AR, Luke DP }}</ref>

Other researchers of the entities seemingly encountered by DMT users describe them as "entities" or "beings" in humanoid as well as animal form, with descriptions of "little people" being common (non-human gnomes, elves, imps, etc.).<ref name="Gallimore">{{cite journal |vauthors=Gallimore, A |title=Evolutionary Implications of the Astonishing Psychoactive Effects of ''N'',''N''-Dimethyltryptamine (DMT) |journal=Journal of Scientific Exploration |volume=27 |issue=3 |pages=455–503 |date=2013 |url=https://www.researchgate.net/publication/277281153 |access-date=2016-08-15 |archive-date=2024-05-26 |archive-url=https://web.archive.org/web/20240526041619/https://www.researchgate.net/publication/277281153_ESSAY_Building_Alien_Worlds-_The_Neuropsychological_and_Evolutionary_Implications_of_the_Astonishing_Psychoactive_Effects_of_NN-Dimethyltryptamine_DMT |url-status=live }}{{unreliable source?|date=February 2020}}</ref> Strassman and others have speculated that this form of hallucination may be the cause of alien abduction and extraterrestrial encounter experiences, which may occur through endogenously-occurring DMT.<ref>{{cite journal |vauthors=Luke DP |year=2011 |title=Discarnate entities and dimethyltryptamine (DMT): Psychopharmacology, phenomenology and ontology |url=https://www.scribd.com/doc/70007742/Discarnate-Entities |journal=Journal of the Society for Psychical Research |volume=75 |number=902 |pages=26–42 |access-date=2017-09-10 |archive-date=2016-04-09 |archive-url=https://web.archive.org/web/20160409215620/https://www.scribd.com/doc/70007742/Discarnate-Entities |url-status=live }}</ref><ref>{{cite journal | vauthors = Luke DP |year=2012 |title=Psychoactive substances and paranormal phenomena: A comprehensive review |journal=International Journal of Transpersonal Studies |volume=31 |pages=97–156 |doi=10.24972/ijts.2012.31.1.97 |doi-access=free }}</ref>

Likening them to descriptions of rattling and chattering auditory phenomena described in encounters with the Hayyoth in the Book of Ezekiel, Rick Strassman notes that participants in his studies, when reporting encounters with the alleged entities, have also described loud auditory hallucinations, such as one subject reporting typically "the elves laughing or talking at high volume, chattering, twittering".<ref name="Prophecy 2014"/>

Researchers such as Robin Carhart-Harris and David E. Nichols among others believe that DMT entities are merely illusions and hallucinations.<ref name="Wright2026">{{cite magazine | vauthors = Wright W | date = 4 March 2026 | title = Some People See Aliens While on DMT. Researchers Want to Find Out What They Can Teach Us | magazine = WIRED | url = https://www.wired.com/story/some-people-see-aliens-while-on-dmt-researchers-want-to-find-out-what-they-can-teach-us/ | access-date = 23 April 2026 }}</ref><ref name="McKenna2024">{{cite web | title=The Alchemist: Reflections on a Lifetime of Psychedelic Chemistry | website=McKenna Academy of Natural Philosophy | date=14 February 2024 | url=https://mckenna.academy/mka-podcast/the-alchemist-reflections-on-a-lifetime-of-psychedelic-chemistry/ | quote=[Dave Nichols:] Yeah, the most logical thing would be is that they’re inventions from your unconscious. They’re representations of something that theoretically, I guess if you took a psychedelic and you queried one of these entities, you could say, who are you to it? Or what do you want? And they might just dissolve, or they might say. Might tell you something about yourself that you had been wondering. But I think you’re right. I mean, the most logical scientific explanation is that they’re products of your unconscious that are popped up by these amazing effects of psychedelics.}}</ref><ref name="BrownHuntley2025">{{cite book | vauthors = Brown DJ, Huntley SP | year = 2025 | title = The Illustrated Field Guide to DMT Entities: Machine Elves, Tricksters, Teachers, and Other Interdimensional Beings | publisher = Inner Traditions/Bear | pages = 32–33, 35, 44–45, 108, 110, 113 | isbn = 978-1-64411-920-4 | url = https://books.google.com/books?id=BFUJEQAAQBAJ | access-date = 3 February 2026 | quote = According to DMT researcher Josie Kins, whom I interviewed for this book: [...] However, when I interviewed Josie Kins and asked her about this, she replied: I'm very much a materialist, despite all the psychedelics I've tried. In fact, the more I've tripped, the more certain I've become that these things are produced by the mind. That doesn't reduce the significance of it for me. [...] }}</ref> However, Andrew Gallimore believes that entity encounters are real and genuine interactions with other-dimensional beings.<ref name="Hebbert2023">{{cite web | vauthors = Hebbert S | title=Researchers Are Mapping DMT Dimensions Through DMTx Tech | website=Psychedelic Spotlight | date=9 May 2023 | url=https://psychedelicspotlight.com/researchers-are-mapping-out-new-dimensions-through-dmtx-technology/ | access-date=28 November 2025}}</ref>

====Near-death experiences==== A 2018 study found significant relationships between DMT experiences and near-death experiences (NDE).<ref>{{cite journal | vauthors = Timmermann C, Roseman L, Williams L, Erritzoe D, Martial C, Cassol H, Laureys S, Nutt D, Carhart-Harris R | year = 2018 | title = DMT Models the Near-Death Experience | journal = Frontiers in Psychology | volume = 9 | page = 1424 | doi = 10.3389/fpsyg.2018.01424 | doi-access = free | pmc = 6107838 | pmid = 30174629 }}</ref> A 2019 large-scale study pointed that ketamine, ''Salvia divinorum'', and DMT (and other classical psychedelic substances) may be linked to NDEs due to the semantic similarity of reports associated with the use of psychoactive compounds and NDE narratives, but the study concluded that with the current data it is neither possible to corroborate nor refute the hypothesis that the release of an endogenous ketamine-like neuroprotective agent underlies NDE phenomenology.<ref name="MartialCassolCharland-Verville2019">{{cite journal | vauthors = Martial C, Cassol H, Charland-Verville V, Pallavicini C, Sanz C, Zamberlan F, Vivot RM, Erowid F, Erowid E, Laureys S, Greyson B, Tagliazucchi E | title = Neurochemical models of near-death experiences: A large-scale study based on the semantic similarity of written reports | journal = Consciousness and Cognition | volume = 69 | pages = 52–69 | date = March 2019 | pmid = 30711788 | doi = 10.1016/j.concog.2019.01.011 | s2cid = 73432875 | hdl = 2268/231971 | hdl-access = free }}</ref>

===Physiological effects=== According to a dose-response study in human subjects, dimethyltryptamine administered intravenously slightly elevated blood pressure, heart rate, pupil diameter, and rectal temperature, in addition to elevating blood concentrations of ''beta''-endorphin, corticotropin, cortisol, and prolactin; growth hormone blood levels rose equally in response to all doses of DMT, and melatonin levels were unaffected."<ref name="pmid8297216" />

===Endogenous production and 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.<ref name="pmid13152519">{{cite journal | vauthors = Hoffer A, Osmond H, Smythies J | title = Schizophrenia; a new approach. II. Result of a year's research | journal = The Journal of Mental Science | volume = 100 | issue = 418 | pages = 29–45 | date = January 1954 | pmid = 13152519 | doi = 10.1192/bjp.100.418.29 }}</ref> 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.<ref>{{cite web | date = 8 November 2013 | title = DMT: The psychedelic drug 'produced in your brain' | website = SBS News | publisher = SBS | url = https://www.sbs.com.au/news/dmt-the-psychedelic-drug-produced-in-your-brain | access-date = 27 March 2014 | archive-date = 27 September 2020 | archive-url = https://web.archive.org/web/20200927161206/https://www.sbs.com.au/news/dmt-the-psychedelic-drug-produced-in-your-brain | url-status = live }}</ref> DMT is naturally occurring in small amounts in rat brains, human cerebrospinal fluid, and other tissues of humans and other mammals.<ref name="pmid16095048" /><ref name="pmid289421" /><ref name="pmid20877" /><ref>{{cite news |url=https://www.npr.org/templates/story/story.php?storyId=104240746&sc=fb&cc=fp |title=The God Chemical: Brain Chemistry And Mysticism |newspaper=NPR.org |publisher=NPR |access-date=20 September 2012 |archive-date=8 January 2014 |archive-url=https://web.archive.org/web/20140108195911/http://www.npr.org/templates/story/story.php?storyId=104240746&sc=fb&cc=fp |url-status=live }}</ref> 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.<ref name = "Dean_2019">{{cite journal | vauthors = Dean JG, Liu T, Huff S, Sheler B, Barker SA, Strassman RJ, Wang MM, Borjigin J | date = June 2019 | title = Biosynthesis and Extracellular Concentrations of ''N'',''N''-Dimethyltryptamine (DMT) in Mammalian Brain | journal = Scientific Reports | volume = 9 | issue = 1 | page = 9333 | doi = 10.1038/s41598-019-45812-w | doi-access = free | pmc = 6597727 | pmid = 31249368 | bibcode = 2019NatSR...9.9333D }}</ref> In 2011, Nicholas Cozzi of the University of Wisconsin School of Medicine and Public Health, and three other researchers, concluded that INMT, an enzyme that is associated with the biosynthesis of DMT and endogenous hallucinogens is present in the non-human primate (rhesus macaque) pineal gland, retinal ganglion neurons, and spinal cord.<ref name="Cozzi N.V., Mavlyutov T.A., Thompson M.A., Ruoho A.E. 2011 840.19" /> Neurobiologist Andrew Gallimore suggested in 2013 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.<ref name="Gallimore" />

==Contraindications== {{See also|Psilocybin#Contraindications}}

==Adverse effects== ===Psychological reactions=== DMT may trigger psychological reactions, known colloquially as a "bad trip", such as intense fear, paranoia, anxiety, panic-attacks, and substance-induced psychosis, particularly in predisposed individuals.<ref name="pmid29366418" /><ref name="pmid28868040">{{cite journal | vauthors = Zurina H, Oliver B, Darshan S, Suresh N, Vicknasingam K, Erich S, Johannes K, Borid Q, and Christian M | date = 18 August 2017 | title = Novel Psychoactive Substances-Recent Progress on Neuropharmacological Mechanisms of Action for Selected Drugs | journal = Frontiers in Psychiatry | volume = 8 | page = 152 | doi = 10.3389/fpsyt.2017.00152 | doi-access = free | pmc = 5563308 | pmid = 28868040 }}</ref>{{better source needed|reason=Both of these references refer to ayahuasca; it's doubtful that DMT alone (smoked or by injection) actually lasts long enough for people with normal MAO levels to cause anything but brief fear at the worst due to the suddeness of the experience. These things are also considered part of the ayahuasca experience among other side effects DMT doesn't have by some and either better references are needed or this should be removed and kept on the ayahuasca article.|date=May 2025}}

===Addiction and dependence liability=== DMT, like other serotonergic psychedelics, is considered to be non-addictive with low abuse potential.<ref name="pmid8297217" /> A study examining substance use disorder for the DSM-IV reported that almost no hallucinogens produced dependence, unlike psychoactive drugs of other classes such as stimulants and depressants.<ref name="pmid29366418">{{cite journal | journal = Current Neuropharmacology | volume = 17 | issue = 2 | pages = 1–15 | title = Ayahuasca: Psychological and Physiologic Effects, Pharmacology and Potential Uses in Addiction and Mental Illness | doi = 10.2174/1570159X16666180125095902 | issn = 1875-6190 | vauthors = Jonathan H, Jaime H, Serdar D, and Glen B | year = 2019 | url = https://www.eurekaselect.com/article/88194 | pmid = 29366418 | pmc = 6343205 | access-date = 2023-05-05 | archive-date = 2023-05-05 | archive-url = https://web.archive.org/web/20230505000155/https://www.eurekaselect.com/article/88194 | url-status = live }}</ref><ref>{{cite journal | journal = Addiction | vauthors = Jon M, James L, and Erich L | date = September 1994 | title = The generalizability of the dependence syndrome across substances: an examination of some properties of the proposed DSM-IV dependence criteria | volume = 89 | issue = 9 | pages = 1105–1113 | doi = 10.1111/j.1360-0443.1994.tb02787.x | url = https://onlinelibrary.wiley.com/doi/10.1111/j.1360-0443.1994.tb02787.x | pmid = 7987187 | access-date = 2023-05-05 | archive-date = 2024-05-26 | archive-url = https://web.archive.org/web/20240526041617/https://onlinelibrary.wiley.com/doi/10.1111/j.1360-0443.1994.tb02787.x | url-status = live | url-access = subscription }}</ref> At present, there have been no studies that report drug withdrawal syndrome with termination of DMT, and dependence potential of DMT and the risk of sustained psychological disturbance may be minimal when used infrequently; however, the physiological dependence potential of DMT and ayahuasca has not yet been documented convincingly.<ref>{{cite journal | vauthors = Robert G | title = Risk assessment of ritual use of oral dimethyltryptamine (DMT) and harmala alkaloids | journal = Addiction | volume = 102 | issue = 1 | pages = 24–34 | date = January 2007 | pmid = 17207120 | doi = 10.1111/j.1360-0443.2006.01652.x | url = https://onlinelibrary.wiley.com/doi/10.1111/j.1360-0443.2006.01652.x | access-date = 2023-05-07 | archive-date = 2024-05-26 | archive-url = https://web.archive.org/web/20240526041617/https://onlinelibrary.wiley.com/doi/10.1111/j.1360-0443.2006.01652.x | url-status = live | url-access = subscription }}</ref>

===Tolerance=== Unlike with other classical psychedelics, tolerance does not seem to develop to the subjective effects of DMT.<ref name="CarbonaroGatch2016" /><ref name="Halberstadt2015">{{cite journal | vauthors = Halberstadt AL | title = Recent advances in the neuropsychopharmacology of serotonergic hallucinogens | journal = Behavioural Brain Research | volume = 277 | issue = | pages = 99–120 | date = January 2015 | pmid = 25036425 | doi = 10.1016/j.bbr.2014.07.016 | pmc = 4642895 }}</ref> Studies report that DMT did not exhibit tolerance upon repeated administration of twice a day sessions, separated by 5{{nbsp}}hours, for 5{{nbsp}}consecutive days; field reports suggests a refractory period of only 15 to 30{{nbsp}}minutes, while the plasma levels of DMT was nearly undetectable 30{{nbsp}}minutes after intravenous administration.<ref name="Halberstadt2015" /><ref name="StrassmanQuallsBerg1996">{{cite journal | vauthors = Strassman RJ, Qualls CR, Berg LM | title = Differential tolerance to biological and subjective effects of four closely spaced doses of N,N-dimethyltryptamine in humans | journal = Biological Psychiatry | volume = 39 | issue = 9 | pages = 784–795 | date = May 1996 | pmid = 8731519 | doi = 10.1016/0006-3223(95)00200-6 }}</ref> Another study of four closely spaced DMT infusion sessions with 30{{nbsp}}minute intervals also suggests no tolerance buildup to the psychological effects of the compound, while heart rate responses and neuroendocrine effects were diminished with repeated administration.<ref name="Halberstadt2015" /><ref name="StrassmanQuallsBerg1996" /> Similarly to DMT by itself, tolerance does not appear to develop to ayahuasca.<ref name="DosSantosHallak2024">{{cite journal | vauthors = Dos Santos RG, Hallak JE | date = November 2024 | title = Ayahuasca: pharmacology, safety, and therapeutic effects | journal = CNS Spectrums | volume = 30 | issue = 1 | page = e2 | doi = 10.1017/S109285292400213X | doi-access = free | pmc = 13064705 | pmid = 39564645 }}</ref><ref name="DosSantosGrasaValle2012">{{cite journal | vauthors = Dos Santos RG, Grasa E, Valle M, Ballester MR, Bouso JC, Nomdedéu JF, Homs R, Barbanoj MJ, Riba J | title = Pharmacology of ayahuasca administered in two repeated doses | journal = Psychopharmacology | volume = 219 | issue = 4 | pages = 1039–1053 | date = February 2012 | pmid = 21842159 | doi = 10.1007/s00213-011-2434-x }}</ref> A fully hallucinogenic dose of DMT did not demonstrate cross-tolerance to human subjects who are highly tolerant to LSD;<ref name="RosenbergIsbellMiner1963">{{cite journal |journal=Psychopharmacologia |vauthors=Rosenberg D, Isbell H, Miner E, and Logan C |doi=10.1007/BF00413244 |date=7 August 1963 |title=The effect of N,N-dimethyltryptamine in human subjects tolerant to lysergic acid diethylamide |volume=5 |issue=3 |url=https://link.springer.com/article/10.1007/BF00413244 |pages=223–224 |pmid=14138757 |s2cid=32950588 |access-date=4 May 2023 |archive-date=4 May 2023 |archive-url=https://web.archive.org/web/20230504011825/https://link.springer.com/article/10.1007/BF00413244 |url-status=live |url-access=subscription }}</ref> hence, research suggests that DMT exhibits unique pharmacological properties compared to other classical psychedelics.<ref name="StrassmanQuallsBerg1996" /> Contrary to earlier findings however, subsequent clinical studies employing DMT by continuous intravenous infusion (also known as DMTx) have found rapid and moderate acute tolerance development with DMT.<ref name="VogtLeyErne2023">{{cite journal | vauthors = Vogt SB, Ley L, Erne L, Straumann I, Becker AM, Klaiber A, Holze F, Vandersmissen A, Mueller L, Duthaler U, Rudin D, Luethi D, Varghese N, Eckert A, Liechti ME | date = May 2023 | title = Acute effects of intravenous DMT in a randomized placebo-controlled study in healthy participants | journal = Translational Psychiatry | volume = 13 | issue = 1 | page = 172 | doi = 10.1038/s41398-023-02477-4 | pmc = 10206108 | pmid = 37221177 }}</ref><ref name="LuanEckernäsAshton2024">{{cite journal | vauthors = Luan LX, Eckernäs E, Ashton M, Rosas FE, Uthaug MV, Bartha A, Jagger S, Gascon-Perai K, Gomes L, Nutt DJ, Erritzøe D, Carhart-Harris RL, Timmermann C | title = Psychological and physiological effects of extended DMT | journal = Journal of Psychopharmacology | volume = 38 | issue = 1 | pages = 56–67 | date = January 2024 | pmid = 37897244 | pmc = 10851633 | doi = 10.1177/02698811231196877 }}</ref><ref name="ErneVogtMüller2025">{{cite journal | vauthors = Erne L, Vogt SB, Müller L, Nuraj A, Becker A, Klaiber A, Zuparic M, Varghese N, Eckert A, Rudin D, Luethi D, Liechti ME | title = Acute dose-dependent effects and self-guided titration of continuous N,N-dimethyltryptamine infusions in a double-blind placebo-controlled study in healthy participants | journal = Neuropsychopharmacology | volume = 50 | issue = 6 | pages = 1008–1016 | date = May 2025 | pmid = 39702577 | pmc = 12032411 | doi = 10.1038/s41386-024-02041-8 }}</ref>

===Long-term use=== There have been no serious adverse effects reported on long-term use of DMT, apart from acute cardiovascular events.<ref name="pmid28868040" /> Repeated and one-time administration of DMT produces marked changes in the cardiovascular system,<ref name="pmid28868040" /> with an increase in systolic and diastolic blood pressure; although the changes were not statistically significant, a robust trend towards significance{{clarify|reason=So, no significance. That's like saying my bank account shows a robust trend towards having millions of dollars in it both in terms of total lack of meaning to anyone and in speculatory nature.|date=June 2025}} was observed for systolic blood pressure at high doses.<ref name="pmid11292011">{{cite journal | title = Subjective effects and tolerability of the South American psychoactive beverage Ayahuasca in healthy volunteers | journal = Psychopharmacology | pmid = 11292011 | doi = 10.1007/s002130000606 | date = February 2001 | vauthors = Jordi R, Antoni F, Gloria U, Adelaida M, Rosa A, Maria M, James C, and Mandel B | volume = 154 | issue = 1 | url = https://link.springer.com/article/10.1007/s002130000606 | pages = 85–95 | s2cid = 5556065 | access-date = 2023-05-05 | archive-date = 2023-05-05 | archive-url = https://web.archive.org/web/20230505014511/https://link.springer.com/article/10.1007/s002130000606 | url-status = live | url-access = subscription }}</ref>

==Overdose== There have been cases of death with DMT.<ref name="Thomas2024">{{cite book | vauthors = Thomas K | date = 2024 | title = Toxicology and Pharmacological Interactions of Classic Psychedelics | publisher = Springer Berlin Heidelberg | doi = 10.1007/7854_2024_508 | pmid = 39042251 | series = Current Topics in Behavioral Neurosciences | publication-place = Berlin, Heidelberg }}</ref> In terms of extrapolated human lethal dose based on animal studies and human case reports, the lethal dose of DMT relative to a typical recreational dose is estimated to be 50-fold in the case of oral DMT (as ayahuasca).<ref name="Thomas2024" />

== Interactions == {{See also|Psychedelic drug#Interactions|Trip killer#Serotonergic psychedelic antidotes}}

DMT is inactive when ingested orally due to metabolism by monoamine oxidase (MAO), and DMT-containing drinks such as ayahuasca have been found to contain monoamine oxidase inhibitors (MAOIs), in particular, harmine and harmaline.<ref name="pmid11292011" /> Life-threatening lethalities such as serotonin syndrome (SS) may occur when MAOIs are combined with certain serotonergic medications such as selective serotonin reuptake inhibitor (SSRI) antidepressants.<ref name="CallawayGrob1998">{{cite journal | vauthors = Callaway JC, Grob CS | title = Ayahuasca preparations and serotonin reuptake inhibitors: a potential combination for severe adverse interactions | journal = Journal of Psychoactive Drugs | volume = 30 | issue = 4 | pages = 367–269 | year = 1998 | pmid = 9924842 | doi = 10.1080/02791072.1998.10399712 | url = http://www.mimosahostilis.com/files/Ayahuasca%20and%20SSRI%20Interactions.pdf | access-date = 10 April 2012 | archive-url = https://web.archive.org/web/20120201144245/http://www.mimosahostilis.com/files/Ayahuasca%20and%20SSRI%20Interactions.pdf | archive-date = 1 February 2012 }}</ref><ref name="pmid29366418" /> Serotonin syndrome has also been reported with tricyclic antidepressants (TCAs), certain opioids, certain analgesics, and antimigraine drugs; it is advised to exercise caution when an individual has used dextromethorphan (DXM), MDMA, ginseng, or ''St. John's wort'' recently.<ref name="pmid29366418" />

Chronic use of SSRIs, TCAs, and MAOIs diminish subjective effects of psychedelics due to presumed serotonin 5-HT2A receptors downregulation and/or desensitization secondary to elevated serotonin levels.<ref name="9780192678522-drug-interaction">{{cite book | vauthors = David N, David C | date = 7 March 2023 | chapter = Drug-interaction with psychotropic drugs | title = Psychedelics as Psychiatric Medications | publisher = Oxford University Press | isbn = 978-0-19-267852-2 | url = https://books.google.com/books?id=7lazEAAAQBAJ | access-date = 21 May 2023 | archive-date = 21 May 2023 | archive-url = https://web.archive.org/web/20230521000115/https://books.google.com/books?id=7lazEAAAQBAJ | url-status = live }}</ref>{{rp|145}} However, a clinical study of people with depression found that SSRIs did not diminish the effects of DMT and instead resulted in greater mystical experience, emotional breakthrough, and ego dissolution scores with DMT than in people with depression not on antidepressants.<ref name="JamesJoelAttwooll2024">{{cite journal | vauthors = James E, Joel Z, Attwooll V, Benway T, Good M, Tziras G, Routledge C, Macek T | title=ACNP 63rd Annual Meeting: Poster Abstracts P1-P304: P160. SPL026 (DMT Fumarate) in Combination With Selective Serotonin Reuptake Inhibitors (SSRIs) for Patients With Major Depressive Disorder | journal=Neuropsychopharmacology | volume=49 | issue=S1 | date=2024 | issn=0893-133X | pmid=39643633 | pmc=11627186 | doi=10.1038/s41386-024-02011-0 | doi-access=free | pages=65–235 (155–156) | url=https://www.nature.com/articles/s41386-024-02011-0.pdf | access-date=31 January 2025}}</ref> This was in contrast to previous research finding that SSRIs diminished the effects of serotonergic psychedelics.<ref name="HalmanKongSarris2024">{{Cite journal |vauthors=Halman A, Kong G, Sarris J, Perkins D |date=January 2024 |title=Drug-drug interactions involving classic psychedelics: A systematic review |journal=Journal of Psychopharmacology |volume=38 |issue=1 |pages=3–18 |doi=10.1177/02698811231211219 |pmc=10851641 |pmid=37982394}}</ref>

The interaction between psychedelics and antipsychotics and anticonvulsants are not well documented; however, reports reveal that co-use of psychedelics with mood stabilizers such as lithium may provoke seizure and dissociative effects in individuals with bipolar disorder.<ref>{{cite journal | journal = Drug and Alcohol Dependence | doi = 10.1016/j.drugalcdep.2022.109586 | volume = 239 | date = 1 October 2022 | vauthors = Otto S, Simon G, Richard C, Walter O, Distin L, Peter H | pmid = 35981469 | pmc = 9627432 | title = Prevalence and associations of classic psychedelic-related seizures in a population-based sample| article-number = 109586 }}</ref><ref name="9780192678522-drug-interaction" />{{rp|146}}

The serotonin receptor agonist methysergide (UML-491) has been reported to greatly intensify the effects of DMT.<ref name="TiHKAL" /><ref name="HalmanKongSarris2024" /><ref name="Sai-Halasz1962">{{cite journal | vauthors = Sai-Halasz A | title = The effect of antiserotonin on the experimental psychosis induced by dimethyltryptamine | journal = Experientia | volume = 18 | issue = 3| pages = 137–138 | date = March 1962 | pmid = 14496041 | doi = 10.1007/BF02153861 }}</ref>

==Pharmacology== ===Pharmacodynamics=== {| class="wikitable floatright" style="font-size:small;" |+ {{Nowrap|Activities of DMT}} |- ! Target !! Affinity (Ki, nM) |- | 5-HT1A | 75–>10,000 (Ki) 75–>100,000 ({{Abbrlink|EC50|Half-maximal effective concentration}}) 68–100% ({{Abbrlink|Emax|Maximal efficacy}}) |- | 5-HT1B | 129–>10,000 |- | 5-HT1D | 39–270 |- | 5-HT1E | 456–517 |- | 5-HT1F | {{Abbr|ND|No data}} |- | 5-HT2A | 53–2,323 (Ki) 22–6,325 ({{Abbr|EC50|half-maximal effective concentration}}) 23–105% ({{Abbr|Emax|Maximal efficacy}}) |- | 5-HT2B | 101–184 (Ki) 3,400–>31,600 ({{Abbr|EC50|Half-maximal effective concentration}}) 10.4% ({{Abbr|Emax|Maximal efficacy}}) |- | 5-HT2C | 33–424 (Ki) 31–114 ({{Abbr|EC50|half-maximal effective concentration}}) 85–99% ({{Abbr|Emax|Maximal efficacy}}) |- | 5-HT3 | >10,000 |- | 5-HT4 | {{Abbr|ND|No data}} |- | 5-HT5A | 611–2,135 |- | 5-HT6 | 68–487 |- | 5-HT7 | 88–206 |- | α1A | 1,300–1,745 |- | α1B | 974 |- | α2A | 1,561–2,100 |- | α2B | 258 |- | α2C | 259 |- | β1–β2 | >10,000 |- | D1 | 271–6,000 |- | D2 | 3,000–>10,000 |- | D3 | 6,300–>10,000 |- | D4 | >10,000 |- | D5 | >10,000 |- | H1 | 220 |- | H2–H4 | >10,000 |- | M1–M5 | >10,000 |- | TAAR1 | 2,200–3,300 (Ki) (rodent) 1,200–1,500 ({{Abbr|EC50|Half-maximal effective concentration}}) (rodent) >10,000 ({{Abbr|EC50|Half-maximal effective concentration}}) (human) |- | σ1 | 5,209 |- | σ2 | >10,000 |- | I1 | 650 |- | {{Abbrlink|SERT|Serotonin transporter}} | 3,742–6,000 (Ki) 712–3,100 ({{Abbrlink|IC50|Half-maximal inhibitory concentration}}) 81–114 ({{Abbr|EC50|Half-maximal effective concentration}}) 78% ({{Abbr|Emax|Maximal efficacy}}) |- | {{Abbrlink|NET|Norepinephrine transporter}} | 6,500–>10,000 (Ki) 3,900 ({{Abbr|IC50|Half-maximal inhibitory concentration}}) 4,166 ({{Abbr|EC50|Half-maximal effective concentration}}) {{Abbr|ND|No data}} ({{Abbr|Emax|Maximal efficacy}}) |- | {{Abbrlink|DAT|Dopamine transporter}} | >10,000–22,000 (Ki) 52,000 ({{Abbr|IC50|Half-maximal inhibitory concentration}}) >10,000 ({{Abbr|EC50|Half-maximal effective concentration}}) 5.4% ({{Abbr|Emax|Maximal efficacy}}) |- class="sortbottom" | colspan="2" style="width: 1px; background-color:var(--background-color-notice-subtle,#eaecf0); color:inherit; text-align: center;" | '''Notes:''' The smaller the value, the more avidly the drug binds to the site. Proteins human unless otherwise specified. '''Refs:'''<ref name="PDSPKiDatabase">{{cite web | title=PDSP Database | website=UNC | url=https://pdspdb.unc.edu/databases/pdsp.php?testDDRadio=testDDRadio&testLigandDD=1271&kiAllRadio=all&doQuery=Submit+Query | language=zu | access-date=29 November 2024}}</ref><ref name="BindingDB">{{cite web | vauthors = Liu T | title=BindingDB BDBM50026868 2-(1H-indol-3-yl)-N,N-dimethylethanamine::2-(3-indolyl)ethyldimethylamine::3-(2-dimethylaminoethyl)indole::3-[2-(dimethylamino)ethyl]indole::CHEMBL12420::DMT::N,N-dimethyl-1H-indole-3-ethylamine::N,N-dimethyltryptamine::US20240166618, Compound DMT::WO2023019367, Compound DMT | website=BindingDB | url=https://www.bindingdb.org/rwd/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50026868 | access-date=29 November 2024}}</ref><ref name="CameronOlson2018" /><ref name="HolzeSinghLiechti2024"/><ref name="RickliLuethiReinisch2015">{{cite journal | vauthors = Rickli A, Luethi D, Reinisch J, Buchy D, Hoener MC, Liechti ME | title = Receptor interaction profiles of novel N-2-methoxybenzyl (NBOMe) derivatives of 2,5-dimethoxy-substituted phenethylamines (2C drugs) | journal = Neuropharmacology | volume = 99 | issue = | pages = 546–553 | date = December 2015 | pmid = 26318099 | doi = 10.1016/j.neuropharm.2015.08.034 | url = http://edoc.unibas.ch/56163/1/20170921163006_59c3cceeb8e5d.pdf}}</ref><ref name="RickliMoningHoener2016">{{cite journal | vauthors = Rickli A, Moning OD, Hoener MC, Liechti ME | title = Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens | journal = European Neuropsychopharmacology | volume = 26 | issue = 8 | pages = 1327–1337 | date = August 2016 | pmid = 27216487 | doi = 10.1016/j.euroneuro.2016.05.001 | s2cid = 6685927 | url = http://edoc.unibas.ch/53326/1/20170117174852_587e4af45b658.pdf }}</ref><ref name="pmid20126400" /><ref name="BloughLandavazoDecker2014" /> <ref name="KozellEshlemanSwanson2023">{{cite journal | vauthors = Kozell LB, Eshleman AJ, Swanson TL, Bloom SH, Wolfrum KM, Schmachtenberg JL, Olson RJ, Janowsky A, Abbas AI | title = Pharmacologic Activity of Substituted Tryptamines at 5-Hydroxytryptamine (5-HT)2A Receptor (5-HT2AR), 5-HT2CR, 5-HT1AR, and Serotonin Transporter | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 385 | issue = 1 | pages = 62–75 | date = April 2023 | pmid = 36669875 | pmc = 10029822 | doi = 10.1124/jpet.122.001454 }}</ref><ref name="EshlemanForsterWolfrum2014">{{cite journal | vauthors = Eshleman AJ, Forster MJ, Wolfrum KM, Johnson RA, Janowsky A, Gatch MB | title = Behavioral and neurochemical pharmacology of six psychoactive substituted phenethylamines: mouse locomotion, rat drug discrimination and in vitro receptor and transporter binding and function | journal = Psychopharmacology | volume = 231 | issue = 5 | pages = 875–888 | date = March 2014 | pmid = 24142203 | pmc = 3945162 | doi = 10.1007/s00213-013-3303-6 | url = https://www.researchgate.net/publication/258061356}}</ref><ref name="MarekMakai-BölöniUmbricht2025">{{cite journal | vauthors = Marek GJ, Makai-Bölöni S, Umbricht D, Christian EP, Winters J, Dvorak D, Raines S, Hughes ZA, Austin EW, Klein AK, Leong W, Krol FJ, Graaf AJ, Juachon MJ, Otto ME, Borghans LG, Jacobs G, Kruegel AC, Sporn J | title = A novel psychedelic 5-HT2A receptor agonist GM-2505: The pharmacokinetic, safety, and pharmacodynamic profile from a randomized trial healthy volunteer | journal = Journal of Psychopharmacology | volume = | issue = | article-number = 2698811251378512 | date = October 2025 | pmid = 41099491 | doi = 10.1177/02698811251378512 | hdl = 1887/4298848 | hdl-access = free | pmc = 13198617 }}</ref><ref name="JanowskyEshlemanJohnson2014">{{cite journal | vauthors = Janowsky A, Eshleman AJ, Johnson RA, Wolfrum KM, Hinrichs DJ, Yang J, Zabriskie TM, Smilkstein MJ, Riscoe MK | title = Mefloquine and psychotomimetics share neurotransmitter receptor and 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DMT binds non-selectively with affinities below 0.6 μmol/L to the following serotonin receptors: 5-HT1A,<ref name="pmid19881490">{{cite journal | vauthors = Keiser MJ, Setola V, Irwin JJ, Laggner C, Abbas AI, Hufeisen SJ, Jensen NH, Kuijer MB, Matos RC, Tran TB, Whaley R, Glennon RA, Hert J, Thomas KL, Edwards DD, Shoichet BK, Roth BL | title = Predicting new molecular targets for known drugs | journal = Nature | volume = 462 | issue = 7270 | pages = 175–181 | date = November 2009 | pmid = 19881490 | pmc = 2784146 | doi = 10.1038/nature08506 | bibcode = 2009Natur.462..175K }}</ref><ref name="pmid1828347">{{cite journal | vauthors = Deliganis AV, Pierce PA, Peroutka SJ | title = Differential interactions of dimethyltryptamine (DMT) with 5-HT1A and 5-HT2 receptors | journal = Biochemical Pharmacology | volume = 41 | issue = 11 | pages = 1739–1744 | date = June 1991 | pmid = 1828347 | doi = 10.1016/0006-2952(91)90178-8 }}</ref><ref name="pmid2540505">{{cite journal | vauthors = Pierce PA, Peroutka SJ | title = Hallucinogenic drug interactions with neurotransmitter receptor binding sites in human cortex | journal = Psychopharmacology | volume = 97 | issue = 1 | pages = 118–122 | year = 1989 | pmid = 2540505 | doi = 10.1007/BF00443425 | s2cid = 32936434 }}</ref> 5-HT1B,<ref name="pmid19881490" /><ref name="pmid20126400">{{cite journal | vauthors = Ray TS | title = Psychedelics and the human receptorome | journal = PloS One | volume = 5 | issue = 2 |article-number=e9019 | date = February 2010 | pmid = 20126400 | pmc = 2814854 | doi = 10.1371/journal.pone.0009019 | bibcode = 2010PLoSO...5.9019R | doi-access = free }}</ref> 5-HT1D,<ref name="pmid19881490" /><ref name="pmid2540505" /><ref name="pmid20126400" /> 5-HT2A,<ref name="pmid19881490" /><ref name="pmid2540505" /><ref name="pmid20126400" /><ref name="pmid9768567">{{cite journal | vauthors = Smith RL, Canton H, Barrett RJ, Sanders-Bush E | title = Agonist properties of ''N'',''N''-dimethyltryptamine at serotonin 5-HT2A and 5-HT2C receptors | journal = Pharmacology, Biochemistry, and Behavior | volume = 61 | issue = 3 | pages = 323–330 | date = November 1998 | pmid = 9768567 | doi = 10.1016/S0091-3057(98)00110-5 | s2cid = 27591297 | url = http://crfdl.org:1111/xmlui/bitstream/handle/123456789/17/Agonist%20Properties%20of%20N,N-Dimethyltryptaminenext%20term%20at%20Ser.pdf }}{{Dead link|date=July 2018 |bot=InternetArchiveBot |fix-attempted=yes }}</ref> 5-HT2B,<ref name="pmid19881490" /><ref name="pmid20126400" /> 5-HT2C,<ref name="pmid19881490" /><ref name="pmid20126400" /><ref name="pmid9768567" /> 5-HT6,<ref name="pmid19881490" /><ref name="pmid20126400" /> and 5-HT7.<ref name="pmid19881490" /><ref name="pmid20126400" /> An agonist action has been determined at 5-HT1A,<ref name="pmid1828347" /> 5-HT2A and 5-HT2C.<ref name="pmid19881490" /><ref name="pmid20126400" /><ref name="pmid9768567" /> 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 μmol/L<ref name="pmid20126400" /> and 0.184 μmol/L.<ref name="pmid19881490" /> 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.<ref name="pmid19505264">{{cite journal | vauthors = Rothman RB, Baumann MH | title = Serotonergic drugs and valvular heart disease | journal = Expert Opinion on Drug Safety | volume = 8 | issue = 3 | pages = 317–329 | date = May 2009 | pmid = 19505264 | pmc = 2695569 | doi = 10.1517/14740330902931524 }}</ref><ref name="pmid17202450">{{cite journal|author1-link=Bryan Roth | vauthors = Roth BL | title = Drugs and valvular heart disease | journal = The New England Journal of Medicine | volume = 356 | issue = 1 | pages = 6–9 | date = January 2007 | pmid = 17202450 | doi = 10.1056/NEJMp068265 }}</ref><ref>{{cite journal | vauthors = Urban JD, Clarke WP, von Zastrow M, Nichols DE, Kobilka B, Weinstein H, Javitch JA, Roth BL, Christopoulos A, Sexton PM, Miller KJ, Spedding M, Mailman RB | title = Functional selectivity and classical concepts of quantitative pharmacology | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 320 | issue = 1 | pages = 1–13 | date = January 2007 | pmid = 16803859 | doi = 10.1124/jpet.106.104463 | s2cid = 447937 | url = https://cdr.lib.unc.edu/concern/articles/xs55mf307 | access-date = 2019-07-12 | archive-date = 2020-04-28 | archive-url = https://web.archive.org/web/20200428163253/https://cdr.lib.unc.edu/concern/articles/xs55mf307 | url-status = live }}</ref>

It has also been shown to possess affinity for the dopamine D1, α1-adrenergic, α2-adrenergic, imidazoline-1, and σ1 receptors.<ref name="pmid2540505" /><ref name="pmid20126400" /><ref name="pmid16962229">{{cite journal | vauthors = Burchett SA, Hicks TP | title = The mysterious trace amines: protean neuromodulators of synaptic transmission in mammalian brain | journal = Progress in Neurobiology | volume = 79 | issue = 5–6 | pages = 223–246 | date = August 2006 | pmid = 16962229 | doi = 10.1016/j.pneurobio.2006.07.003 | s2cid = 10272684 | url = http://www.mimosahostilis.com/files/The%20mysterious%20trace%20amines%20%20protean%20neuromodulato.pdf | df = dmy-all | oclc = 231983957 | archive-date = 1 February 2012 | archive-url = https://web.archive.org/web/20120201112618/http://www.mimosahostilis.com/files/The%20mysterious%20trace%20amines%20%20protean%20neuromodulato.pdf }}</ref> Converging lines of evidence established activation of the σ1 receptor at concentrations of 50–100 μmol/L.<ref name="pmid19213917">{{cite journal | vauthors = Fontanilla D, Johannessen M, Hajipour AR, Cozzi NV, Jackson MB, Ruoho AE | title = The hallucinogen ''N'',''N''-dimethyltryptamine (DMT) is an endogenous sigma-1 receptor regulator | journal = Science | volume = 323 | issue = 5916 | pages = 934–937 | date = February 2009 | pmid = 19213917 | pmc = 2947205 | doi = 10.1126/science.1166127 | bibcode = 2009Sci...323..934F }}</ref> Its efficacies at the other receptor binding sites are unclear. It has also been shown ''in vitro'' to be a substrate for the cell-surface serotonin transporter (SERT) expressed in human platelets, and the rat vesicular monoamine transporter 2 (VMAT2), which was transiently expressed in fall armyworm Sf9 cells. DMT inhibited SERT-mediated serotonin uptake into platelets at an average concentration of 4.00 ± 0.70 μmol/L and VMAT2-mediated serotonin uptake at an average concentration of 93 ± 6.8 μmol/L.<ref name="pmid19756361">{{cite journal | vauthors = Cozzi NV, Gopalakrishnan A, Anderson LL, Feih JT, Shulgin AT, Daley PF, Ruoho AE | title = Dimethyltryptamine and other hallucinogenic tryptamines exhibit substrate behavior at the serotonin uptake transporter and the vesicle monoamine transporter | journal = Journal of Neural Transmission | volume = 116 | issue = 12 | pages = 1591–1599 | date = December 2009 | pmid = 19756361 | doi = 10.1007/s00702-009-0308-8 | s2cid = 15928043 | url = http://www.neurophys.wisc.edu/~cozzi/Hallucinogenic%20tryptamines%20as%20SERT%20and%20VMAT2%20substrates.%20%20Cozzi.%20%20J.%20Neural%20Transm.,%20116,%201591-1599%20(2009).pdf | access-date = 20 November 2010 | archive-url = https://web.archive.org/web/20100617172010/http://www.neurophys.wisc.edu/~cozzi/Hallucinogenic%20tryptamines%20as%20SERT%20and%20VMAT2%20substrates.%20%20Cozzi.%20%20J.%20Neural%20Transm.,%20116,%201591-1599%20(2009).pdf | archive-date = 17 June 2010 }}</ref> In addition, DMT is a potent serotonin releasing agent with an {{Abbrlink|EC50|half-maximal effective concentration}} value of 81–114{{nbsp}}nM and an {{Abbrlink|Emax|maximal efficacy}} of 78%.<ref name="MarekMakai-BölöniUmbricht2025" /><ref name="BloughLandavazoDecker2014">{{cite journal | vauthors = Blough BE, Landavazo A, Decker AM, Partilla JS, Baumann MH, Rothman RB | title = Interaction of psychoactive tryptamines with biogenic amine transporters and serotonin receptor subtypes | journal = Psychopharmacology | volume = 231 | issue = 21 | pages = 4135–4144 | date = October 2014 | pmid = 24800892 | pmc = 4194234 | doi = 10.1007/s00213-014-3557-7 }}</ref><ref name="US11440879" />

As with other so-called "classical hallucinogens",<ref name="nida1994">{{cite book | vauthors = Glennon RA | year = 1994 | veditors = Lin GC, Glennon RA | chapter = Classical hallucinogens: an introductory overview | title = Hallucinogens: An Update | publisher = U.S. Dept. of Health and Human Services, Public Health Service, National Institutes of Health, National Institute on Drug Abuse | volume = 146 | page = 4 | archive-date = 2011-07-25 | archive-url = https://web.archive.org/web/20110725203539/http://crfdl.org:1111/xmlui/bitstream/handle/123456789/288/hallucinogens%20an%20update.pdf | chapter-url = http://crfdl.org:1111/xmlui/bitstream/handle/123456789/288/hallucinogens%20an%20update.pdf | series = NIDA Research Monograph Series | location = Rockville, MD }}</ref> a large part of DMT psychedelic effects can be attributed to a functionally selective activation of the 5-HT2A receptor.<ref name="pmid8297216" /><ref name="pmid19881490" /><ref name="pmid17977517">{{cite journal | vauthors = Fantegrossi WE, Murnane KS, Reissig CJ | title = The behavioral pharmacology of hallucinogens | journal = Biochemical Pharmacology | volume = 75 | issue = 1 | pages = 17–33 | date = January 2008 | pmid = 17977517 | pmc = 2247373 | doi = 10.1016/j.bcp.2007.07.018 }}</ref><ref name="pmid14761703">{{cite journal | vauthors = Nichols DE | title = Hallucinogens | journal = Pharmacology & Therapeutics | volume = 101 | issue = 2 | pages = 131–181 | date = February 2004 | pmid = 14761703 | doi = 10.1016/j.pharmthera.2003.11.002 }}</ref><ref name="pmid9875725">{{cite journal | vauthors = Vollenweider FX, Vollenweider-Scherpenhuyzen MF, Bäbler A, Vogel H, Hell D | title = Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action | journal = Neuroreport | volume = 9 | issue = 17 | pages = 3897–3902 | date = December 1998 | pmid = 9875725 | doi = 10.1097/00001756-199812010-00024 | s2cid = 37706068 }}</ref><ref name="pmid8788488">{{cite journal | vauthors = Strassman RJ | title = Human psychopharmacology of ''N'',''N''-dimethyltryptamine | journal = Behavioural Brain Research | volume = 73 | issue = 1–2 | pages = 121–124 | year = 1996 | pmid = 8788488 | doi = 10.1016/0166-4328(96)00081-2 | s2cid = 4047951 | url = http://crfdl.org:1111/xmlui/bitstream/handle/123456789/373/Beh_Brain_Res_96.pdf }}{{Dead link|date=July 2018 |bot=InternetArchiveBot |fix-attempted=yes }}</ref><ref name="pmid6513725">{{cite journal | vauthors = Glennon RA, Titeler M, McKenney JD | title = Evidence for 5-HT2 involvement in the mechanism of action of hallucinogenic agents | journal = Life Sciences | volume = 35 | issue = 25 | pages = 2505–2511 | date = December 1984 | pmid = 6513725 | doi = 10.1016/0024-3205(84)90436-3 }}</ref> DMT concentrations eliciting 50% of its maximal effect (half maximal effective concentration = EC50) at the human 5-HT2A receptor ''in vitro'' are in the 0.118–0.983 μmol/L range.<ref name="pmid19881490" /><ref name="pmid20126400" /><ref name="pmid9768567" /><ref name="pmid9023266">{{cite journal | vauthors = Roth BL, Choudhary MS, Khan N, Uluer AZ | date = February 1997 | title = High-affinity agonist binding is not sufficient for agonist efficacy at 5-hydroxytryptamine2A receptors: evidence in favor of a modified ternary complex model | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 280 | issue = 2 | pages = 576–583 | doi = 10.1016/S0022-3565(24)36476-6 | pmid = 9023266 | url = http://jpet.aspetjournals.org/content/280/2/576.full.pdf | access-date = 2010-11-29 | archive-date = 2024-05-26 | archive-url = https://web.archive.org/web/20240526042118/http://jpet.aspetjournals.org/content/280/2/576.full.pdf | url-status = live }}</ref> 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).

DMT is one of the only psychedelics that isn't known to produce tolerance to its hallucinogenic effects.<ref name="Halberstadt2015" /><ref name="JiménezBouso2022" /> The lack of tolerance with DMT may be related to the fact that, unlike other psychedelics such as LSD and DOI, DMT does not desensitize serotonin 5-HT2A receptors ''in vitro''.<ref name="Halberstadt2015" /><ref name="pmid9768567" /> This may be due to the fact that DMT is a biased agonist of the serotonin 5-HT2A receptor.<ref name="JiménezBouso2022">{{cite journal | vauthors = Jiménez JH, Bouso JC | title = Significance of mammalian N, N-dimethyltryptamine (DMT): A 60-year-old debate | journal = Journal of Psychopharmacology | volume = 36 | issue = 8 | pages = 905–919 | date = August 2022 | pmid = 35695604 | doi = 10.1177/02698811221104054 }}</ref><ref name="BloughLandavazoDecker2014" /> More specifically, DMT activates the Gq signaling pathway of the serotonin 5-HT2A receptor without significantly recruiting β-arrestin2.<ref name="JiménezBouso2022" /><ref name="BloughLandavazoDecker2014" /> Activation of β-arrestin2 is linked to receptor downregulation and tachyphylaxis.<ref name="JiménezBouso2022" /><ref name="BarksdaleDossFonzo2024">{{cite journal | vauthors = Barksdale BR, Doss MK, Fonzo GA, Nemeroff CB | title = The mechanistic divide in psychedelic neuroscience: An unbridgeable gap? | journal = Neurotherapeutics | volume = 21 | issue = 2 | article-number = e00322 | date = March 2024 | pmid = 38278658 | doi = 10.1016/j.neurot.2024.e00322 | pmc = 10963929 }}</ref><ref name="WallachCaoCalkins2023">{{cite journal | vauthors = Wallach J, Cao AB, Calkins MM, Heim AJ, Lanham JK, Bonniwell EM, Hennessey JJ, Bock HA, Anderson EI, Sherwood AM, Morris H, de Klein R, Klein AK, Cuccurazzu B, Gamrat J, Fannana T, Zauhar R, Halberstadt AL, McCorvy JD | date = December 2023 | title = Identification of 5-HT2A receptor signaling pathways associated with psychedelic potential | journal = Nature Communications | volume = 14 | issue = 1 | page = 8221 | doi = 10.1038/s41467-023-44016-1 | pmc = 10724237 | pmid = 38102107 | bibcode = 2023NatCo..14.8221W }}</ref> Similarly to DMT, 5-MeO-DMT is a biased agonist of the serotonin 5-HT2A receptor, with minimal β-arrestin2 recruitment, and likewise has been associated with little tolerance to its hallucinogenic effects.<ref name="ErmakovaDunbarRucker2022">{{cite journal | vauthors = Ermakova AO, Dunbar F, Rucker J, Johnson MW | title = A narrative synthesis of research with 5-MeO-DMT | journal = Journal of Psychopharmacology | volume = 36 | issue = 3 | pages = 273–294 | date = March 2022 | pmid = 34666554 | doi = 10.1177/02698811211050543 | pmc = 8902691 }}</ref><ref name="BloughLandavazoDecker2014" /> On the other hand, the lack of apparent tolerance of DMT and similar agents may simply be related to their very short durations.<ref name="Martin_1977">{{cite book | vauthors = Martin WR, Sloan JW | date = 1977 | chapter = Pharmacology and Classification of LSD-like Hallucinogens | title = Drug Addiction II: Amphetamine, Psychotogen, and Marihuana Dependence | publisher = Springer Berlin Heidelberg | pages = 305–368 | isbn = 978-3-642-66711-4 | doi = 10.1007/978-3-642-66709-1_3 | publication-place = Berlin, Heidelberg | chapter-url = https://books.google.com/books?id=gb_uCAAAQBAJ&pg=PA305 | quote = The observation that tolerance to LSD does not confer cross tolerance to several of DMT's autonomic effects suggests that these N-disubstituted compounds may differ in some respects from LSD. The duration of action of DMT is less than that of LSD. Further, we have not been able to demonstrate tachyphylaxis to the actions of tryptamine in the dog (MARTIN and EADES, 1972). Tryptamine's duration of action is less than that of DMT. It is possible that a long duration of action is a necessary attribute of LSD-like hallucinogens for them to effectively induce tolerance (see Subsect. E.III). }}</ref>

As DMT has been shown to have slightly better potency (EC50) at the human serotonin 5-HT2C receptor than at the serotonin 5-HT2A receptor,<ref name="pmid20126400" /><ref name="pmid9768567" /> the serotonin 5-HT2C receptor is also implicated in DMT's effects.<ref name="pmid14761703" /><ref name="pmid20165943">{{cite journal | vauthors = Canal CE, Olaghere da Silva UB, Gresch PJ, Watt EE, Sanders-Bush E, Airey DC | title = The serotonin 2C receptor potently modulates the head-twitch response in mice induced by a phenethylamine hallucinogen | journal = Psychopharmacology | volume = 209 | issue = 2 | pages = 163–174 | date = April 2010 | pmid = 20165943 | pmc = 2868321 | doi = 10.1007/s00213-010-1784-0 }}</ref> The drug shows pronounced biased agonism at the serotonin 5-HT2C receptor.<ref name="BonniwellAlabadaliHennessey2025">{{cite journal | vauthors = Bonniwell EM, Alabdali R, Hennessey JJ, McKee JL, Cavalco NG, Lammers JC, Moore EJ, Franchini L, Orlandi C, McCorvy JD | title = Serotonin 5-HT2C Receptor Signaling Analysis Reveals Psychedelic Biased Agonism | journal = ACS Chemical Neuroscience | volume = 16 | issue = 19 | pages = 3899–3914 | date = October 2025 | pmid = 40944639 | doi = 10.1021/acschemneuro.5c00647 | pmc = 12629614 }}</ref> Other receptors such as the serotonin 5-HT1A receptor<ref name="pmid2540505" /><ref name="pmid14761703" /><ref name="pmid8788488" /> and the sigma σ1 receptor may also play a role.<ref name="pmid19213917" /><ref name="pmid19278957">{{cite journal | vauthors = Su TP, Hayashi T, Vaupel DB | date = March 2009 | title = When the endogenous hallucinogenic trace amine ''N'',''N''-dimethyltryptamine meets the sigma-1 receptor | journal = Science Signaling | volume = 2 | issue = 61 | page = pe12 | doi = 10.1126/scisignal.261pe12 | pmc = 3155724 | pmid = 19278957 }}</ref>

In 2009, it was hypothesized that DMT may be an endogenous ligand for the σ1 receptor.<ref name="pmid19213917" /><ref name="pmid19278957" /> The concentration of DMT needed for σ1 activation ''in vitro'' (50–100 μmol/L) is similar to the behaviorally active concentration measured in mouse brain of approximately 106 μmol/L<ref name="pmid6798607">{{cite journal | vauthors = Morinan A, Collier JG | title = Effects of pargyline and SKF-525A on brain ''N'',''N''-dimethyltryptamine concentrations and hyperactivity in mice | journal = Psychopharmacology | volume = 75 | issue = 2 | pages = 179–183 | year = 1981 | pmid = 6798607 | doi = 10.1007/BF00432184 | s2cid = 43576890 }}</ref> 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,<ref name="pmid19756361" /> such concentrations might occur during vesicular release. To illustrate, while the ''average'' concentration of serotonin in brain tissue is in the 1.5-4 μmol/L range,<ref name="pmid20723248" /><ref name="pmid16146432" /> the concentration of serotonin in synaptic vesicles was measured at 270 mM.<ref name="pmid11086995">{{cite journal | vauthors = Bruns D, Riedel D, Klingauf J, Jahn R | title = Quantal release of serotonin | journal = Neuron | volume = 28 | issue = 1 | pages = 205–220 | date = October 2000 | pmid = 11086995 | doi = 10.1016/S0896-6273(00)00097-0 | hdl-access = free | hdl = 11858/00-001M-0000-0029-D137-5 | s2cid = 6364237 }}</ref> Following vesicular release, the resulting concentration of serotonin in the synaptic cleft, to which serotonin receptors are exposed, is estimated to be about 300 μmol/L. 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.

In September 2020, an ''in vitro'' and ''in vivo'' study found that DMT present in the ayahuasca infusion promotes neurogenesis, meaning it helps with generating neurons.<ref>{{cite journal | vauthors = Morales García JA, Calleja Conde J, López Moreno JA, Alonso Gil S, Sanz San Cristobal M, Riba J, Pérez Castillo A | date = September 2020 | title = ''N'',''N''-Dimethyltryptamine compound found in the hallucinogenic tea ayahuasca, regulates adult neurogenesis in vitro and in vivo | journal = Translational Psychiatry | volume = 10 | issue = 1 | page = 331 | doi = 10.1038/s41398-020-01011-0 | pmc = 7522265 | pmid = 32989216 }}</ref>

DMT produces the head-twitch response (HTR), a behavioral proxy of psychedelic-like effects, in rodents.<ref name="CameronOlson2018" /><ref name="CarbonaroGatch2016" /><ref name="CanalMorgan2012">{{cite journal | vauthors = Canal CE, Morgan D | title = Head-twitch response in rodents induced by the hallucinogen 2,5-dimethoxy-4-iodoamphetamine: a comprehensive history, a re-evaluation of mechanisms, and its utility as a model | journal = Drug Testing and Analysis | volume = 4 | issue = 7–8 | pages = 556–576 | date = July 2012 | pmid = 22517680 | pmc = 3722587 | doi = 10.1002/dta.1333 }}</ref><ref name="HalberstadtChathaKlein2020">{{cite journal | vauthors = Halberstadt AL, Chatha M, Klein AK, Wallach J, Brandt SD | title = Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species | journal = Neuropharmacology | volume = 167 | issue = | article-number = 107933 | date = May 2020 | pmid = 31917152 | pmc = 9191653 | doi = 10.1016/j.neuropharm.2019.107933 | url = http://usdbiology.com/cliff/Courses/Advanced%20Seminars%20in%20Neuroendocrinology/Serotonergic%20Psychedelics%2020/Halberstadt%2020%20Neuropharm%20potency%20of%20hallucinogens%20%20head-twitch.pdf | archive-date = 2025-03-26 | access-date = 2025-03-27 | archive-url = https://web.archive.org/web/20250326111621/http://usdbiology.com/cliff/Courses/Advanced%20Seminars%20in%20Neuroendocrinology/Serotonergic%20Psychedelics%2020/Halberstadt%2020%20Neuropharm%20potency%20of%20hallucinogens%20%20head-twitch.pdf | url-status = dead }}</ref> However, its effects in the HTR paradigm in mice that are highly strain-dependent, including producing an HTR comparable to other psychedelics, producing an HTR that is much weaker than that of other psychedelics, or producing no HTR at all.<ref name="CameronOlson2018" /><ref name="CarbonaroGatch2016" /><ref name="CanalMorgan2012" /> These conflicting results may be due to rapid metabolism of DMT and/or other peculiarities of DMT in different species.<ref name="CarbonaroGatch2016" /> Besides the HTR, DMT also substitutes for LSD and DOM in rodent drug discrimination tests.<ref name="HalberstadtChathaKlein2020" />

DMT has been found to be a psychoplastogen, a compound capable of promoting rapid and sustained neuroplasticity that may have wide-ranging therapeutic benefit.<ref>{{cite journal | vauthors = Ly C, Greb AC, Cameron LP, Wong JM, Barragan EV, Wilson PC, Burbach KF, Soltanzadeh Zarandi S, Sood A, Paddy MR, Duim WC, Dennis MY, McAllister AK, Ori-McKenney KM, Gray JA, Olson DE | title = Psychedelics Promote Structural and Functional Neural Plasticity | journal = Cell Reports | volume = 23 | issue = 11 | pages = 3170–3182 | date = June 2018 | pmid = 29898390 | pmc = 6082376 | doi = 10.1016/j.celrep.2018.05.022 }}</ref>

The cryo-EM structures of the serotonin 5-HT2A receptor with DMT, as well as with various other psychedelics and serotonin 5-HT2A receptor agonists, have been solved and published by Bryan L. Roth and colleagues.<ref name="GumpperJainKim2025">{{cite journal | vauthors = Gumpper RH, Jain MK, Kim K, Sun R, Sun N, Xu Z, DiBerto JF, Krumm BE, Kapolka NJ, Kaniskan HÜ, Nichols DE, Jin J, Fay JF, Roth BL | date = March 2025 | title = The structural diversity of psychedelic drug actions revealed | journal = Nature Communications | volume = 16 | issue = 1 | page = 2734 | doi = 10.1038/s41467-025-57956-7 | pmc = 11923220 | pmid = 40108183 | bibcode = 2025NatCo..16.2734G }}</ref><ref name="GumpperDiBertoJain2022">{{cite conference | vauthors = Gumpper RH, DiBerto J, Jain M, Kim K, Fay J, Roth BL | title = Structures of Hallucinogenic and Non-Hallucinogenic Analogues of the 5-HT2A Receptor Reveals Molecular Insights into Signaling Bias | conference = University of North Carolina at Chapel Hill Department of Pharmacology Research Retreat September 16th, 2022 – William and Ida Friday Center | date = September 2022 | url = https://www.med.unc.edu/pharm/wp-content/uploads/sites/930/2022/07/COMPLETE-PHARM-RETREAT-PROGRAM-2022-UPDATE.pdf#page=37}}</ref>

===Pharmacokinetics=== ====Absorption==== When taken orally, DMT is metabolized by monoamine oxidase (MAO) enzymes in the liver and gut, and is thus not orally bioavailable unless a monoamine oxidase inhibitor (MAOI) is taken (as is naturally found in the ayahuasca brew).<ref name="McKennaTowers1984b" /> As such, DMT by itself is instead taken by parenteral administration.<ref name="TiHKAL" />

Closely coextending with peak psychedelic effects, the mean time to reach peak concentration (''T''max) has been determined to be 10 to 15{{nbsp}}minutes in whole blood after intramuscular injection,<ref name="pmid4607811" /> and 2 to 3{{nbsp}}minutes after intravenous administration.<ref name="pmid8297216" /><ref name="ErneMuellerStraumann2026" /> When taken orally mixed in an ayahuasca decoction or in freeze-dried ayahuasca gel caps, DMT ''T''max is considerably delayed to 1.8{{nbsp}}hours on average,<ref name="pmid10404423">{{cite journal | vauthors = Callaway JC, McKenna DJ, Grob CS, Brito GS, Raymon LP, Poland RE, Andrade EN, Andrade EO, Mash DC | title = Pharmacokinetics of Hoasca alkaloids in healthy humans | journal = Journal of Ethnopharmacology | volume = 65 | issue = 3 | pages = 243–256 | date = June 1999 | pmid = 10404423 | doi = 10.1016/S0378-8741(98)00168-8 | bibcode = 1999JEthn..65..243C | url = http://wiki.dmt-nexus.com/w/images/2/26/Pharmacokinetics_of_hoasca_in_healthy_humans.pdf }}{{Dead link|date=July 2018 |bot=InternetArchiveBot |fix-attempted=yes }}</ref> and 1.5 to 2{{nbsp}}hours,<ref name="pmid12660312">{{cite journal | vauthors = Riba J, Valle M, Urbano G, Yritia M, Morte A, Barbanoj MJ | title = Human pharmacology of ayahuasca: subjective and cardiovascular effects, monoamine metabolite excretion, and pharmacokinetics | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 306 | issue = 1 | pages = 73–83 | date = July 2003 | pmid = 12660312 | doi = 10.1124/jpet.103.049882 | s2cid = 6147566 }}</ref> respectively.<ref name="McKennaTowers1984b"/>

DMT peak level concentrations (''C''max) measured in the blood after intramuscular (IM) injection (0.7{{nbsp}}mg/kg, ''n'' = 11)<ref name="pmid4607811">{{cite journal | vauthors = Kaplan J, Mandel LR, Stillman R, Walker RW, VandenHeuvel WJ, Gillin JC, Wyatt RJ | title = Blood and urine levels of ''N'',''N''-dimethyltryptamine following administration of psychoactive dosages to human subjects | journal = Psychopharmacologia | volume = 38 | issue = 3 | pages = 239–245 | year = 1974 | pmid = 4607811 | doi = 10.1007/BF00421376 | s2cid = 12346844 }}</ref> and in plasma following intravenous administration (0.4{{nbsp}}mg/kg, ''n'' = 10)<ref name="pmid8297216" /> of fully psychedelic doses are in the range of around 14 to 154{{nbsp}}μg/L and 32 to 204{{nbsp}}μg/L, respectively. The corresponding molar concentrations of DMT are therefore in the range of 0.074–0.818{{nbsp}}μmol/L in whole blood and 0.170–1.08{{nbsp}}μmol in plasma.

====Distribution==== DMT easily crosses the blood–brain barrier.<ref name="Brito-da-CostaDias-da-SilvaGomes2020" /> Studies on the llipophilicity of DMT have been contradictory – most studies find DMT to be either lipophilic or slightly lipophilic, but a 2023 study found it to be lipophobic.<ref name="vanderHeijdenOttoSchoones2025">{{cite journal | vauthors = van der Heijden KV, Otto ME, Schoones JW, van Esdonk MJ, Borghans LG, van Hasselt JG, van Gerven JM, Jacobs G | title = Clinical Pharmacokinetics of N,N-Dimethyltryptamine (DMT): A Systematic Review and Post-hoc Analysis | journal = Clinical Pharmacokinetics | volume = 64 | issue = 2 | pages = 215–227 | date = February 2025 | pmid = 39838235 | doi = 10.1007/s40262-024-01450-8 | pmc = 11782443 }}</ref>

Several studies have described active transport and accumulation of DMT into rat and dog brains following peripheral administration.<ref name="pmid6812592">{{cite journal | vauthors = Barker SA, Beaton JM, Christian ST, Monti JA, Morris PE | title = Comparison of the brain levels of ''N'',''N''-dimethyltryptamine and ''alpha'',''alpha'',''beta'',''beta''-tetradeutero-''N'',''N''-dimethyltryptamine following intraperitoneal injection. The in vivo kinetic isotope effect | journal = Biochemical Pharmacology | volume = 31 | issue = 15 | pages = 2513–2516 | date = August 1982 | pmid = 6812592 | doi = 10.1016/0006-2952(82)90062-4 }}</ref><ref name="pmid41604">{{cite journal | vauthors = Sangiah S, Gomez MV, Domino EF | title = Accumulation of ''N'',''N''-dimethyltryptamine in rat brain cortical slices | journal = Biological Psychiatry | volume = 14 | issue = 6 | pages = 925–936 | date = December 1979 | pmid = 41604 }}</ref><ref name="pmid3472526">{{cite journal | vauthors = Sitaram BR, Lockett L, Talomsin R, Blackman GL, McLeod WR | title = In vivo metabolism of 5-methoxy-''N'',''N''-dimethyltryptamine and ''N'',''N''-dimethyltryptamine in the rat | journal = Biochemical Pharmacology | volume = 36 | issue = 9 | pages = 1509–1512 | date = May 1987 | pmid = 3472526 | doi = 10.1016/0006-2952(87)90118-3 }}</ref><ref name="pmid3866749">{{cite journal | vauthors = Takahashi T, Takahashi K, Ido T, Yanai K, Iwata R, Ishiwata K, Nozoe S | title = 11C-labeling of indolealkylamine alkaloids and the comparative study of their tissue distributions | journal = The International Journal of Applied Radiation and Isotopes | volume = 36 | issue = 12 | pages = 965–969 | date = December 1985 | pmid = 3866749 | doi = 10.1016/0020-708X(85)90257-1 }}</ref><ref name="pmid3489620">{{cite journal | vauthors = Yanai K, Ido T, Ishiwata K, Hatazawa J, Takahashi T, Iwata R, Matsuzawa T | title = In vivo kinetics and displacement study of a carbon-11-labeled hallucinogen, ''N'',''N''-[11C]dimethyltryptamine | journal = European Journal of Nuclear Medicine | volume = 12 | issue = 3 | pages = 141–146 | year = 1986 | pmid = 3489620 | doi = 10.1007/BF00276707 | s2cid = 20030999 }}</ref> Similar active transport and accumulation processes likely occur in human brains 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 μmol/L range.<ref name="pmid20723248">{{cite journal | vauthors = Best J, Nijhout HF, Reed M | date = August 2010 | title = Serotonin synthesis, release and reuptake in terminals: a mathematical model | journal = Theoretical Biology & Medical Modelling | volume = 7 | issue = 1 | page = 34 | doi = 10.1186/1742-4682-7-34 | doi-access = free | pmc = 2942809 | pmid = 20723248 }}</ref><ref name="pmid16146432">{{cite journal | vauthors = Merrill MA, Clough RW, Jobe PC, Browning RA | title = Brainstem seizure severity regulates forebrain seizure expression in the audiogenic kindling model | journal = Epilepsia | volume = 46 | issue = 9 | pages = 1380–1388 | date = September 2005 | pmid = 16146432 | doi = 10.1111/j.1528-1167.2005.39404.x | s2cid = 23783863 | url = http://assets0.pubget.com/pdf/16146432.pdf | archive-url = https://web.archive.org/web/20181031214030/http://assets0.pubget.com/pdf/16146432.pdf | archive-date = 31 October 2018 }}</ref>

====Metabolism==== DMT is primarily metabolized by monoamine oxidase A (MAO-A) into indole-3-acetic acid (IAA) and to a much lesser extent in the liver by CYP2D6 and CYP2C19.<ref name="vanderHeijdenOttoSchoones2025" /><ref name="CYOP">{{cite journal | vauthors = Eckernäs E, Macan-Schönleben A, Andresen-Bergström M, Birgersson S, Hoffmann KJ, Ashton M | title = ''N, N''-dimethyltryptamine forms oxygenated metabolites via CYP2D6 - an ''in vitro'' investigation | journal = Xenobiotica; The Fate of Foreign Compounds in Biological Systems | volume = 53 | issue = 8–9 | pages = 515–522 | date = December 2023 | pmid = 37916667 | doi = 10.1080/00498254.2023.2278488 | hdl = 10067/2011610151162165141 | hdl-access = free }}</ref> When taken intravenously, DMT is primarily metabolized by MAO-A in the circulatory system and brain.<ref name="GoodJoelBenway2023" /> When smoked, a more substantial fraction (possibly as high as 10–20%) is metabolized in the liver by CYP2D6 and CYP2C19.<ref>{{cite journal | vauthors = Riba J, McIlhenny EH, Bouso JC, Barker SA | title = Metabolism and urinary disposition of N,N-dimethyltryptamine after oral and smoked administration: a comparative study | journal = Drug Testing and Analysis | volume = 7 | issue = 5 | pages = 401–406 | date = May 2015 | pmid = 25069786 | doi = 10.1002/dta.1685 }}</ref>

====Elimination==== DMT is eliminated in urine.<ref name="Brito-da-CostaDias-da-SilvaGomes2020" /> The elimination half-life after intravenous injection is 6 to 12{{nbsp}}minutes.<ref name="GoodJoelBenway2023">{{cite journal | vauthors = Good M, Joel Z, Benway T, Routledge C, Timmermann C, Erritzoe D, Weaver R, Allen G, Hughes C, Topping H, Bowman A, James E | title = Pharmacokinetics of N,N-dimethyltryptamine in Humans | journal = European Journal of Drug Metabolism and Pharmacokinetics | volume = 48 | issue = 3 | pages = 311–327 | date = May 2023 | pmid = 37086340 | doi = 10.1007/s13318-023-00822-y | pmc = 10122081 }}</ref><ref name="ErneMuellerStraumann2026">{{cite journal | vauthors = Erne L, Mueller L, Straumann I, Ademaj B, Eckert A, Vukalovic I, Valenta J, Luethi D, Liechti ME, Vogt SB | date = March 2026 | title = Dose-dependent pharmacokinetics and acute effects of intravenous bolus N,N-dimethyltryptamine: double-blind, randomized versus open-label dose-escalation administration study in healthy participants | journal = Translational Psychiatry | volume = 16 | issue = 1 | page = 213 | doi = 10.1038/s41398-026-03987-7 | doi-access = free | pmc = 13039932 | pmid = 41896202 }}</ref>

==Chemistry== thumb|DMT crystals

===Appearance and form=== DMT is commonly handled and stored as a hemifumarate,<ref name="TiHKAL" /><ref name="pmid32608093">{{cite journal | vauthors = Cozzi NV, Daley PF | title = Synthesis and characterization of high-purity ''N'',''N''-dimethyltryptamine hemifumarate for human clinical trials | journal = Drug Testing and Analysis | volume = 12 | issue = 10 | pages = 1483–1493 | date = October 2020 | doi = 10.1002/dta.2889| pmid = 32608093 | s2cid = 220290037 }}</ref> as other DMT acid salts are extremely hygroscopic and will not readily crystallize. Its freebase form, although less stable than DMT hemifumarate, is favored by recreational users choosing to vaporize the chemical as it has a lower boiling point.<ref name="TiHKAL" />

DMT is a lipophilic compound, with an experimental log P of 2.57.<ref name="Brito-da-CostaDias-da-SilvaGomes2020">{{cite journal | vauthors = Brito-da-Costa AM, Dias-da-Silva D, Gomes NG, Dinis-Oliveira RJ, Madureira-Carvalho Á | title = Toxicokinetics and Toxicodynamics of Ayahuasca Alkaloids N,N-Dimethyltryptamine (DMT), Harmine, Harmaline and Tetrahydroharmine: Clinical and Forensic Impact | journal = Pharmaceuticals | volume = 13 | issue = 11 | date = October 2020 | page = 334 | pmid = 33114119 | pmc = 7690791 | doi = 10.3390/ph13110334 | doi-access = free }}</ref>

===Laboratory synthesis=== The chemical synthesis of DMT has been described.<ref name="CameronOlson2018" /><ref name="TiHKAL" /> It can be synthesized through several possible pathways from different starting materials. The two most commonly encountered synthetic routes are through the reaction of indole with oxalyl chloride followed by reaction with dimethylamine and reduction of the carbonyl functionalities with lithium aluminium hydride to form DMT.<ref name="TiHKAL" /> 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.<ref>{{cite journal | vauthors = Bosch J, Roca T, Armengol M, Fernández-Forner D |title=Synthesis of 5-(sulfamoylmethyl)indoles |journal=Tetrahedron |date=4 February 2001 |volume=57 |issue=6 |pages=1041–1048 |doi=10.1016/S0040-4020(00)01091-7 }}</ref> 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 or methanol) also result in the creation of cyanated tryptamine and ''beta''-carboline byproducts of unknown toxicity while using sodium borohydride in absence of acid does not.<ref>{{cite journal | vauthors = Brandt SD, Moore SA, Freeman S, Kanu AB | title = Characterization of the synthesis of ''N'',''N''-dimethyltryptamine by reductive amination using gas chromatography ion trap mass spectrometry | journal = Drug Testing and Analysis | volume = 2 | issue = 7 | pages = 330–338 | date = July 2010 | pmid = 20648523 | doi = 10.1002/dta.142 }}</ref> Bufotenine, a plant extract, can also be synthesized into DMT.<ref>{{cite journal | vauthors = Moreira LA, Murta MM, Gatto CC, Fagg CW, dos Santos ML | date = April 2015 | title = Concise synthesis of ''N'',''N''-dimethyltryptamine and 5-methoxy-''N'',''N''-dimethyltryptamine starting with bufotenine from Brazilian Anadenanthera ssp | journal = Natural Product Communications | volume = 10 | issue = 4 | article-number = 1934578X1501000411 | doi = 10.1177/1934578X1501000411 | doi-access = free | pmid = 25973481 | s2cid = 34076965 }}</ref>

Alternatively, an excess of methyl iodide or methyl ''p''-toluenesulfonate and sodium carbonate can be used to over-methylate tryptamine, resulting in the creation of a quaternary ammonium salt, which is then dequaternized (demethylated) in ethanolamine to yield DMT. The same two-step procedure is used to synthesize other ''N'',''N''-dimethylated compounds, such as 5-MeO-DMT.<ref>{{cite web | url=https://hyperlab.info/inv/index.php?lang=en&act=ST&f=17&t=913&st=120 | title=Hyperlab.info -> Мелатонин и 5-MeO-DMT | access-date=2023-09-27 | archive-date=2023-09-27 | archive-url=https://web.archive.org/web/20230927010145/https://hyperlab.info/inv/index.php?lang=en&act=ST&f=17&t=913&st=120 | url-status=live }}</ref>

===Clandestine manufacture=== right|thumb|DMT during various stages of purification

In a clandestine setting, DMT is not typically synthesized due to the lack of availability of the starting materials, namely tryptamine and oxalyl chloride. Instead, it is more often extracted from plant-sources using a nonpolar hydrocarbon solvent such as naphtha or heptane, and a base such as sodium hydroxide.{{citation needed | date = June 2023}}

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

A variety of plants contain DMT at sufficient levels for being viable sources<ref name="CarbonaroGatch2016" /> such as ''Mimosa tenuiflora, Acacia acuminata,'' ''Acacia confusa,'' ''Acacia maidenii'', ''Arundo donax'', '''Diplopterys cabrerana'', ''Psychotria viridis''.

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.

===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.{{Citation needed|reason=Such precise values range needs one or more reliable sources|date=January 2012}} Less than 0.1% of an oral dose is eliminated unchanged in the 24-hour urine of humans.<ref>{{cite journal | vauthors = Callaway JC, Raymon LP, Hearn WL, McKenna DJ, Grob CS, Brito GS, Mash DC | title = Quantitation of ''N'',''N''-dimethyltryptamine and harmala alkaloids in human plasma after oral dosing with ayahuasca | journal = Journal of Analytical Toxicology | volume = 20 | issue = 6 | pages = 492–497 | date = October 1996 | pmid = 8889686 | doi = 10.1093/jat/20.6.492 | doi-access = free }}</ref><ref>{{cite book | vauthors = Baselt R | date = 2011 | title = Disposition of Toxic Drugs and Chemicals in Man | publisher = Biomedical Publications | edition = 9th | pages = 525–526 | isbn = 978-0-9626523-8-7 | location = Seal Beach, CA }}</ref>{{Clarify|date=March 2014|reason=unclear language, eliminated unchanged?}}

====Indolethylamine ''N''-methyltransferase (INMT)==== Before techniques of molecular biology were used to localize indolethylamine ''N''-methyltransferase (INMT),<ref name="pmid9852119" /><ref name="pmid10552930" /> characterization and localization went on a par: samples of the biological material where INMT is hypothesized to be active are subject to enzyme assay. Those enzyme assays are performed either with a radiolabeled methyl donor like (14C-CH3)SAM to which known amounts of unlabeled substrates like tryptamine are added<ref name="pmid779022" /> or with addition of a radiolabeled substrate like (14C)NMT to demonstrate ''in vivo'' formation.<ref name="pmid6792104" /><ref name="pmid14361" /> 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. The essentially qualitative method thin layer chromatography (TLC) was thus used in a vast majority of studies.<ref name="pmid779022" /> 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<ref name="pmid5150167">{{cite journal | vauthors = Mandel LR, Rosenzweig S, Kuehl FA | title = Purification and substrate specificity of indoleamine-''N''-methyl transferase | journal = Biochemical Pharmacology | volume = 20 | issue = 3 | pages = 712–716 | date = March 1971 | pmid = 5150167 | doi = 10.1016/0006-2952(71)90158-4 }}</ref><ref name="pmid1056183">{{cite journal | vauthors = Lin R, Narasimhachari N | title = ''N''-Methylation of 1-methyltryptamines by indolethylamine ''N''-methyltransferase | journal = Biochemical Pharmacology | volume = 24 | issue = 11–12 | pages = 1239–1240 | date = June 1975 | pmid = 1056183 | doi = 10.1016/0006-2952(75)90071-4 }}</ref> and human<ref name="pmid5034200">{{cite journal | vauthors = Mandel LR, Ahn HS, VandenHeuvel WJ | title = Indoleamine-''N''-methyl transferase in human lung | journal = Biochemical Pharmacology | volume = 21 | issue = 8 | pages = 1197–1200 | date = April 1972 | pmid = 5034200 | doi = 10.1016/0006-2952(72)90113-X }}</ref> lung during the early 1970s.

Selectivity rather than sensitivity proved to be a challenge 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,<ref name="pmid779022" /><ref name="pmid6792104" /><ref name="pmid1067427">{{cite journal | vauthors = Rosengarten H, Meller E, Freidhoff AJ | title = Possible source of error in studies of enzymatic formation of dimethyltryptamine | journal = Journal of Psychiatric Research | volume = 13 | issue = 1 | pages = 23–30 | year = 1976 | pmid = 1067427 | doi = 10.1016/0022-3956(76)90006-6 }}</ref> and negligible amounts of DMT in brain tissue.<ref name="pmid779022" /> 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.<ref name="pmid779022" /> These findings are a blow for all previous claims of evidence of INMT activity and DMT biosynthesis in avian<ref name="pmid5793241">{{cite journal | vauthors = Morgan M, Mandell AJ | title = Indole(ethyl)amine ''N''-methyltransferase in the brain | journal = Science | volume = 165 | issue = 3892 | pages = 492–493 | date = August 1969 | pmid = 5793241 | doi = 10.1126/science.165.3892.492 | bibcode = 1969Sci...165..492M | s2cid = 43317224 }}</ref> and mammalian brain,<ref name="pmid5279043">{{cite journal | vauthors = Mandell AJ, Morgan M | title = Indole(ethyl)amine ''N''-methyltransferase in human brain | journal = Nature | volume = 230 | issue = 11 | pages = 85–87 | date = March 1971 | pmid = 5279043 | doi = 10.1038/newbio230085a0 }}</ref><ref name="pmid4703789">{{cite journal | vauthors = Saavedra JM, Coyle JT, Axelrod J | title = The distribution and properties of the nonspecific ''N''-methyltransferase in brain | journal = Journal of Neurochemistry | volume = 20 | issue = 3 | pages = 743–752 | date = March 1973 | pmid = 4703789 | doi = 10.1111/j.1471-4159.1973.tb00035.x | s2cid = 42038762 }}</ref> including {{lang|la|in vivo}},<ref name="pmid5059565">{{cite journal | vauthors = Saavedra JM, Axelrod J | title = Psychotomimetic ''N''-methylated tryptamines: formation in brain in vivo and in vitro | journal = Science | volume = 175 | issue = 4028 | pages = 1365–1366 | date = March 1972 | pmid = 5059565 | doi = 10.1126/science.175.4028.1365 | url = http://crfdl.org:1111/xmlui/bitstream/handle/123456789/392/1733285.pdf?sequence=1 | format = PDF | bibcode = 1972Sci...175.1365S | s2cid = 30864349 }}{{Dead link|date=July 2018 |bot=InternetArchiveBot |fix-attempted=yes }}</ref><ref name="pmid4725358">{{cite journal | vauthors = Wu PH, Boulton AA | title = Distribution and metabolism of tryptamine in rat brain | journal = Canadian Journal of Biochemistry | volume = 51 | issue = 7 | pages = 1104–1112 | date = July 1973 | pmid = 4725358 | doi = 10.1139/o73-144 }}</ref> as they all relied upon use of the problematic TLC methods:<ref name="pmid779022" /> 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.<ref name="pmid963555">{{cite journal | vauthors = Boarder MR, Rodnight R | title = Tryptamine-''N''-methyltransferase activity in brain tissue: a re-examination | journal = Brain Research | volume = 114 | issue = 2 | pages = 359–364 | date = September 1976 | pmid = 963555 | doi = 10.1016/0006-8993(76)90680-6 | s2cid = 36334101 }}</ref><ref name="pmid823298">{{cite journal | vauthors = Gomes UR, Neethling AC, Shanley BC | title = Enzymatic N-methylation of indoleamines by mammalian brain: fact or artefact? | journal = Journal of Neurochemistry | volume = 27 | issue = 3 | pages = 701–705 | date = September 1976 | pmid = 823298 | doi = 10.1111/j.1471-4159.1976.tb10397.x | s2cid = 6043841 }}</ref> Published in 1978, the last study attempting to evidence {{lang|la|in vivo}} INMT activity and DMT production in brain (rat) with TLC methods finds biotransformation of radiolabeled tryptamine into DMT to be real but "insignificant".<ref name="pmid279646">{{cite journal | vauthors = Stramentinoli G, Baldessarini RJ | title = Lack of enhancement of dimethyltryptamine formation in rat brain and rabbit lung in vivo by methionine or ''S''-adenosylmethionine | journal = Journal of Neurochemistry | volume = 31 | issue = 4 | pages = 1015–1020 | date = October 1978 | pmid = 279646 | doi = 10.1111/j.1471-4159.1978.tb00141.x | s2cid = 26099031 }}</ref> Capability of the method used in this latter study to resolve DMT from tetrahydro-β-carbolines is questioned later.<ref name="pmid6792104"/>

To localize INMT, a qualitative leap is accomplished with use of modern techniques of molecular biology, and of immunohistochemistry. In humans, a gene encoding INMT is determined to be located on chromosome 7.<ref name="pmid10552930" /> Northern blot analyses reveal INMT messenger RNA (mRNA) to be highly expressed in rabbit lung,<ref name="pmid9852119" /> and in human thyroid, adrenal gland, and lung.<ref name="pmid10552930" /><ref name="UniProtO95050">{{cite web|url=https://www.uniprot.org/uniprot/O95050|title=INMT – Indolethylamine ''N''-methyltransferase – ''Homo sapiens'' (Human) – INMT gene & protein|website=Uniprot.org|access-date=2018-03-24|archive-date=2018-09-20|archive-url=https://web.archive.org/web/20180920111803/https://www.uniprot.org/uniprot/O95050|url-status=live}}</ref> Intermediate levels of expression are found in human heart, skeletal muscle, trachea, stomach, small intestine, pancreas, testis, prostate, placenta, lymph node, and spinal cord.<ref name="pmid10552930" /><ref name="UniProtO95050" /> Low to very low levels of expression are noted in rabbit brain,<ref name="pmid10552930" /> and human thymus, liver, spleen, kidney, colon, ovary, and bone marrow.<ref name="pmid10552930" /><ref name="UniProtO95050" /> INMT mRNA expression is absent in human peripheral blood leukocytes, whole brain, and in tissue from seven specific brain regions (thalamus, subthalamic nucleus, caudate nucleus, hippocampus, amygdala, substantia nigra, and corpus callosum).<ref name="pmid10552930" /><ref name="UniProtO95050" /> 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.<ref name="Cozzi N.V., Mavlyutov T.A., Thompson M.A., Ruoho A.E. 2011 840.19">{{cite journal | vauthors = Cozzi NV, Mavlyutov TA, Thompson MA, Ruoho AE | date = 2011 | title = Indolethylamine N-methyltransferase expression in primate nervous tissue. | journal = Society for Neuroscience Abstracts | volume = 37 | page = 840.19 | url = http://www.neurophys.wisc.edu/~cozzi/Indolethylamine%20N-methyltransferase%20expression%20in%20primate%20nervous%20tissue.pdf | access-date = 20 September 2012 | archive-date = 13 September 2012 | archive-url = https://web.archive.org/web/20120913184820/http://www.neurophys.wisc.edu/~cozzi/Indolethylamine%20N-methyltransferase%20expression%20in%20primate%20nervous%20tissue.pdf }}</ref> 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.<ref name = "Dean_2019" />

===Analogues and derivatives=== {{See also|Substituted tryptamine}}

Numerous analogues and derivatives of DMT are known.<ref name="TiHKAL" /> Some examples include tryptamine (T), ''N''-methyltryptamine (NMT), serotonin (5-hydroxytryptamine; 5-HT), psilocin (4-HO-DMT), psilocybin (4-PO-DMT), 4-AcO-DMT (psilacetin), 4-PrO-DMT, bufotenin (5-HO-DMT or ''N'',''N''-dimethylserotonin), and 5-MeO-DMT (mebufotenin; ''N'',''N'',''O''-trimethylserotonin).<ref name="TiHKAL" /> Some further examples include methylethyltryptamine (MET), diethyltryptamine (DET), methylpropyltryptamine (MPT), dipropyltryptamine (DPT), methylisopropyltryptamine (MiPT), diisopropyltryptamine (DiPT), methylallyltryptamine (MALT), diallyltryptamine (DALT), and pyr-T (''N'',''N''-tetramethylenetryptamine) and their derivatives.<ref name="TiHKAL" />

Some lesser-known DMT derivatives include 1-methyl-DMT, lespedamine (1-MeO-DMT), 2-methyl-DMT, 4-methyl-DMT, 4-MeO-DMT, 4-fluoro-DMT, 5-methyl-DMT, 5-ethyl-DMT, 5-TFM-DMT, 5-EtO-DMT, 5-TFMO-DMT, 5-fluoro-DMT, 5-chloro-DMT, 5-bromo-DMT, 6-fluoro-DMT, 5,6-dibromo-DMT, 4,5-MDO-DMT, 4,5-DHP-DMT, 5,6-MDO-DMT, 5-MeS-DMT, 6-methyl-DMT, 6-HO-DMT, 6-MeO-DMT, 7-methyl-DMT, 7-MeO-DMT, NBoc-DMT (NB-DMT), α,''N'',''N''-TMT (α-Me-DMT), and α,''N'',''N'',''O''-TeMS (5-MeO-α-Me-DMT).<ref name="TiHKAL" />

Cyclized tryptamines containing DMT in their chemical structures include ibogalogs like ibogainalog and tabernanthalog; iboga alkaloids like ibogaine and noribogaine; lysergamides like ergine (LSA) and lysergic acid diethylamide (LSD); and partial ergolines and lysergamides like ''N''-DEAOP-NMT, 10,11-seco-LSD, RU-28306 (4,α-methylene-DMT), RU-28251 (4,α-methylene-DPT), Bay R 1531 (LY-197206; 4,α-methylene-5-MeO-DPT), and NDTDI (8,10-seco-LSD), among others.<ref name="TiHKAL" /> β-Carbolines and harmala alkaloids like harmine and harmaline contain DMT's close analogue NMT embedded in their structures.<ref name="TiHKAL" /> Triptans like sumatriptan, rizatriptan, eletriptan, almotriptan, frovatriptan, and zolmitriptan, which are antimigraine agents, all contain DMT in their structures.<ref name="TekesSzegiHashemi2013">{{cite journal | vauthors = Tekes K, Szegi P, Hashemi F, Laufer R, Kalász H, Siddiq A, Ertsey C | title = Medicinal chemistry of antimigraine drugs | journal = Current Medicinal Chemistry | volume = 20 | issue = 26 | pages = 3300–3316 | date = 2013 | pmid = 23746273 | doi = 10.2174/0929867311320260012 }}</ref><ref name="Allen2025">{{cite web | vauthors = Allen AK | title=Psychedelics potential set to extend beyond mental health | website=Pharmaceutical Technology | date=10 November 2025 | url=https://www.pharmaceutical-technology.com/features/psychedelics-outside-mental-health/ | access-date=13 November 2025 | quote="When you look at molecules like psilocybin, lysergic acid diethylamide (LSD) or dimethyltryptamine (DMT), they are all almost identical to approved headache medications in terms of their chemical structure and pharmacological profile," Schindler states.}}</ref> Similarly, the pertine antipsychotics including alpertine, milipertine, oxypertine, and solypertine are DMT derivatives.

Bioisosteres of DMT in which the indole ring system has been replaced with a different ring system include isoDMT (an isoindole or isotryptamine), 2ZEDMA (an indolizine), and C-DMT (an indene), among others. The homologues of DMT in which the alkyl side chain has been shortened or lengthened by one carbon atom are gramine and dimethylhomotryptamine (DMHT), respectively.<ref name="TiHKAL" /> Further-extended homologues are also known.<ref name="NicholsGlennon1984">{{cite book | vauthors = Nichols DE, Glennon RA | date = 1984 | veditors = Jacobs BL | chapter = Medicinal Chemistry and Structure-Activity Relationships of Hallucinogens | title = Hallucinogens: Neurochemical, Behavioral, and Clinical Perspectives | publisher = Raven Press | pages = 95–142 | isbn = 978-0-89004-990-7 | url = https://books.google.com/books?id=EdpsAAAAMAAJ&pg=PA95 | location = New York | oclc = 10324237 | chapter-url = https://bitnest.netfirms.com/external/Books/HallucinogensNBCP95 | quote = Lengthening of the side chain of DMT by a single methylene group produces N,N-dimethylhomotryptamine (DMHT; 76, R = H, n = 3). which produced hyperthermia when administered to rabbits (7,232) but was found to be inactive in man (235). Intravenous administration of 5 and 10 mg and intramuscular injection of 20 to 70 mg DMHT was without psychologic effect in 10 human subjects (235). Additional studies on DMHT homologs (i.e., 76, n = 4–10) did not show any interesting activity (7,232). }}</ref>

Deuterated isotopologues of DMT include deudimethyltryptamine (DMT-d10) or CYB004 (HLP004),<ref name="WHO2026">{{cite web | url = https://cdn.who.int/media/docs/default-source/international-nonproprietary-names-(inn)/pl134.pdf | title = WHO2026 | website = cdn.who.int }}</ref><ref name="VartyMorganGiardino2023">{{cite journal | vauthors = Varty G, Morgan M, Giardino O, Krakowsky J, Mueller T, Canal C, Pathare P, Avery K, Nivorozhkin A, Palfreyman M | title = ACNP 62nd Annual Meeting: Poster Abstracts P1 - P250: P80. Preclinical Characterization of CYB004: A Novel, Deuterated N,N-Dimethyltryptamine (DMT) Analog for the Potential Treatment of Generalized Anxiety Disorder (GAD) | journal = Neuropsychopharmacology | volume = 48 | issue = Suppl 1 | pages = 63–210 (109–110) | date = December 2023 | pmid = 38040809 | pmc = 10729595 | doi = 10.1038/s41386-023-01755-5 | publisher = Springer Science and Business Media LLC | doi-access = free }}</ref><ref name="InamdarvanderHeijdenNathan2023">{{cite journal | vauthors = Inamdar A, van der Heijden K, Nathan P, Reichelt A, Hegle A, Otto M, Pathare P, House-Gecewicz A, Bartlone A, Zuiker R, Giardino O, Varty G, Morgan M, Muhammad A, Krempien S, Avery K, Nivorozhkin A, Palfreyman M, Jacobs G | date = December 2023 | title = ACNP 62nd Annual Meeting: Poster Abstracts P251 – P500: P425. Early Clinical Development of a Deuterated N,N-Dimethyltryptamine (DMT) Analog for the Treatment of Mental Health Conditions | journal = Neuropsychopharmacology | volume = 48 | issue = Suppl 1 | pages = 211–354 (310–311) | doi = 10.1038/s41386-023-01756-4 | pmid = 38040810 | pmc = 10729596 | url = https://www.helus.com/wp-content/uploads/2025/04/ERLY_ACNP-2023-CYB004-Inamdar-Early-Clinical-Development-of-a-Deuterated-NN-Dimethyltryptamine-DMT-Analog.pdf}}</ref> SPL028 (D2-DMT; α,α-dideutero-DMT),<ref name="AdisInsight-SPL028">{{cite web | title = SPL 028 | date = 16 February 2024 | website = AdisInsight | url = https://adisinsight.springer.com/drugs/800063710 | access-date = 27 July 2025 }}</ref><ref name="Layzell_2023">{{cite journal | vauthors = Layzell M, Rands P, Good M, Joel Z, Cousins R, Benway T, James E, Routledge C | title = Discovery and In Vitro Characterization of SPL028: Deuterated N , N -Dimethyltryptamine | journal = ACS Medicinal Chemistry Letters | volume = 14 | issue = 9 | pages = 1216–1223 | date = 14 September 2023 | pmid = 37736183 | pmc = 10510671 | doi = 10.1021/acsmedchemlett.3c00143 | issn = 1948-5875 | doi-access = free }}</ref><ref name="Kargbo_2022">{{cite journal | vauthors = Kargbo RB | title = Application of Deuterated N , N -Dimethyltryptamine in the Potential Treatment of Psychiatric and Neurological Disorders | journal = ACS Medicinal Chemistry Letters | volume = 13 | issue = 9 | pages = 1402–1404 | date = 8 September 2022 | pmid = 36105328 | pmc = 9465894 | doi = 10.1021/acsmedchemlett.2c00354 | issn = 1948-5875 | doi-access = free }}</ref> and DMT-d4 (α,α,β,β-tetradeutero-DMT).<ref name="Barker2018">{{cite journal | vauthors = Barker SA | date = 2018 | title = N, N-Dimethyltryptamine (DMT), an Endogenous Hallucinogen: Past, Present, and Future Research to Determine Its Role and Function | journal = Frontiers in Neuroscience | volume = 12 | page = 536 | doi = 10.3389/fnins.2018.00536 | doi-access = free | pmc = 6088236 | pmid = 30127713 }}</ref><ref name="BeatonBarkerLiu1982">{{cite journal | vauthors = Beaton JM, Barker SA, Liu WF | title = A comparison of the behavioral effects of proteo-and deutero-N, N-dimethyltryptamine | journal = Pharmacology, Biochemistry, and Behavior | volume = 16 | issue = 5 | pages = 811–814 | date = May 1982 | pmid = 6806829 | doi = 10.1016/0091-3057(82)90240-4 | url = }}</ref><ref name="pmid6812592" /><ref name="BarkerBeatonChristian1984">{{cite journal | vauthors = Barker SA, Beaton JM, Christian ST, Monti JA, Morris PE | title = In vivo metabolism of alpha,alpha,beta,beta-tetradeutero-N, N-dimethyltryptamine in rodent brain | journal = Biochemical Pharmacology | volume = 33 | issue = 9 | pages = 1395–1400 | date = May 1984 | pmid = 6587850 | doi = 10.1016/0006-2952(84)90404-0 | url = }}</ref> Prodrugs of DMT such as 1-benzoyl-DMT and ''N''-phosphonooxymethyl-DMT (''N''-POM-DMT) have also been described.<ref name="Kargbo2023">{{cite journal | vauthors = Kargbo RB | date = April 2023 | title = Orally Active Forms of DMT, 5-MeO-DMT, and Long-Acting MDMA for the Treatment of Neuropsychiatric Disorders | journal = ACS Medicinal Chemistry Letters | volume = 14 | issue = 4 | pages = 367–368 | doi = 10.1021/acsmedchemlett.3c00077 | pmc = 10108390 | pmid = 37077395 | quote = Parent DMT and 5-MeO−DMT suffer from inherent pharmacokinetic limitations: DMT has an ultrashort half-life (t1/2 = 8−13 min in mice) and is orally inactive without MAOI coadministration, while 5-MeO−DMT also requires MAOI to achieve meaningful oral exposure. To overcome these barriers, Terran Biosciences has developed proprietary prodrugs designed for single oral dosing that bypass first-pass metabolism and subsequently potentially improve CNS delivery after bioconversion (WO2023283364A2).50 Preclinical data demonstrate the success of this approach: oral administration of a DMT prodrug (compound Exp. 2−17, 10 mg/kg) in rats achieved a t1/2 of {{Strikethrough|1.24 h}} [10.3 h] for DMT, whereas parent DMT given orally is essentially inactive without MAOI coadministration. Similarly, a 5-MeO−DMT prodrug (Exp. 2− 19, 10 mg/kg) yielded a Cmax of 106 ng/mL, and a t1/2 of 2.02 h for 5-MeO−DMT.50 }}</ref><ref name="ZhangLinWang2026">{{cite journal | vauthors = Zhang T, Lin C, Wang X | date = 25 May 2026 | title = Overcoming Pharmacokinetic and Peripheral Safety Challenges in Psychedelic Therapies: The Promise of Advanced Drug Delivery Systems | journal = ACS Pharmacology & Translational Science | doi = 10.1021/acsptsci.6c00146 | issn = 2575-9108 }}</ref><ref name="WO2023283364">{{cite web | title=N,n-dimethyltryptamine and related psychedlics and uses thereof | website=Google Patents | date=7 July 2022 | url=https://patents.google.com/patent/WO2023283364 | access-date=29 May 2026}}</ref><ref name="PalfreymanVartyStang2025">{{cite journal | vauthors = Palfreyman MG, Varty GB, Stang E, Boltaev U, Avery K, Nivorozhkin A | title = Modification of natural tryptamines for the treatment of neuropsychiatric diseases | journal = Journal of Psychopharmacology | volume = 39 | issue = 12 | pages = 1338–1350 | date = December 2025 | pmid = 41045211 | doi = 10.1177/02698811251368362 | url = | quote = In addition to psilocin, DMT and 5-MeO-DMT have been made into prodrugs despite lacking the 4-hydroxyl group attachment point. [...] In another approach, the dimethylamino group of DMT or 5-MeO-DMT has been used to generate betaine-like prodrugs of these classic psychedelics (e.g., see N-phosphonooxymethyl prodrugs of DMT and 5-MeO-DMT in Table 3 (Khan et al., 2024)).}}</ref><ref name="US20240287107">{{cite web | title=Prodrugs of dimethyltryptamine and derivatives thereof | website=Google Patents | date=1 May 2024 | url=https://patents.google.com/patent/US20240287107A1/en | access-date=30 May 2026}}</ref>

Many of DMT's analogues and derivatives are serotonin receptor modulators and/or serotonergic psychedelics similarly to DMT itself.<ref name="TiHKAL" />

==Natural occurrence== ===Evidence in mammals=== Publishing in ''Science'' in 1961, Julius Axelrod found an ''N''-methyltransferase enzyme capable of mediating biotransformation of tryptamine into DMT in a rabbit's lung.<ref name="pmid13685339" /> This finding initiated a still ongoing scientific interest in endogenous DMT production in humans and other mammals.<ref name="pmid779022" /><ref name="pmid16095048">{{cite journal | vauthors = Kärkkäinen J, Forsström T, Tornaeus J, Wähälä K, Kiuru P, Honkanen A, Stenman UH, Turpeinen U, Hesso A | title = Potentially hallucinogenic 5-hydroxytryptamine receptor ligands bufotenine and dimethyltryptamine in blood and tissues | journal = Scandinavian Journal of Clinical and Laboratory Investigation | volume = 65 | issue = 3 | pages = 189–199 | date = April 2005 | pmid = 16095048 | doi = 10.1080/00365510510013604 | s2cid = 20005294 }}</ref> 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.<ref name="pmid779022" />

In 2013, researchers reported DMT in the pineal gland microdialysate of rodents.<ref name="pmid23881860">{{cite journal | vauthors = Barker SA, Borjigin J, Lomnicka I, Strassman R | title = LC/MS/MS analysis of the endogenous dimethyltryptamine hallucinogens, their precursors, and major metabolites in rat pineal gland microdialysate | journal = Biomedical Chromatography | volume = 27 | issue = 12 | pages = 1690–1700 | date = December 2013 | pmid = 23881860 | doi = 10.1002/bmc.2981 | url = https://deepblue.lib.umich.edu/bitstream/2027.42/101767/1/bmc2981.pdf | hdl = 2027.42/101767 | hdl-access = free | access-date = 2018-04-20 | archive-date = 2024-05-26 | archive-url = https://web.archive.org/web/20240526042116/https://deepblue.lib.umich.edu/bitstream/2027.42/101767/1/bmc2981.pdf | url-status = live }}</ref>

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.<ref name="pmid24508833">{{cite journal | vauthors = Gomes MM, Coimbra JB, Clara RO, Dörr FA, Moreno AC, Chagas JR, Tufik S, Pinto E, Catalani LH, Campa A | title = Biosynthesis of ''N'',''N''-dimethyltryptamine (DMT) in a melanoma cell line and its metabolization by peroxidases | journal = Biochemical Pharmacology | volume = 88 | issue = 3 | pages = 393–401 | date = April 2014 | pmid = 24508833 | doi = 10.1016/j.bcp.2014.01.035 | doi-access = free }}</ref>

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,{{Citation needed|date=July 2021}} the amount being 2.5–3.4 mg/kg. Contrarily, 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.<ref name= "pmid29095071">{{cite journal | vauthors = Nichols, DE | date = November 2017 | title = ''N'',''N''-Dimethyltryptamine and the pineal gland: Separating fact from myth | journal = Journal of Psychopharmacology | volume = 32 | issue = 1 | pages = 30–36 | doi = 10.1177/0269881117736919 | doi-access = free | pmid = 29095071 }}</ref>

In 2014, researchers demonstrated the immunomodulatory potential of DMT and 5-MeO-DMT through the Sigma-1 receptor of human immune cells. This immunomodulatory activity may contribute to significant anti-inflammatory effects and tissue regeneration.<ref name="pmid25171370">{{cite journal | vauthors = Szabo A, Kovacs A, Frecska E, Rajnavolgyi E | title = Psychedelic ''N'',''N''-dimethyltryptamine and 5-methoxy-''N'',''N''-dimethyltryptamine modulate innate and adaptive inflammatory responses through the sigma-1 receptor of human monocyte-derived dendritic cells | journal = PloS One | volume = 9 | issue = 8 |article-number=e106533 | date = 29 August 2014 | pmid = 25171370 | pmc = 4149582 | doi = 10.1371/journal.pone.0106533 | bibcode = 2014PLoSO...9j6533S | doi-access = free }}</ref>

====Endogenous DMT==== ''N'',''N''-Dimethyltryptamine (DMT), a psychedelic compound identified endogenously in mammals, is biosynthesized by aromatic {{sc|L}}-amino acid decarboxylase (AADC) and indolethylamine-''N''-methyltransferase (INMT). Studies have investigated brain expression of INMT transcript in rats and humans, coexpression 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.<ref name="Dean_2019" />

The first claimed detection of endogenous DMT in mammals was published in June 1965: German researchers F. Franzen and H. Gross report to have evidenced and quantified DMT, along with its structural analog bufotenin (5-HO-DMT), in human blood and urine.<ref name="pmid5839067">{{cite journal | vauthors = Franzen F, Gross H | title = Tryptamine, ''N'',''N''-dimethyltryptamine, ''N'',''N''-dimethyl-5-hydroxytryptamine and 5-methoxytryptamine in human blood and urine | journal = Nature | volume = 206 | issue = 988 | page = 1052 | date = June 1965 | pmid = 5839067 | doi = 10.1038/2061052a0 | quote = After the elaboration of sufficiently selective and quantitative procedures, which are discussed elsewhere, we were able to study the occurrence of tryptamine, ''N'',''N''-dimethyltryptamine, ''N'',''N''-dimethyl-5-hydroxytryptamine and 5-hydroxytryptamine in normal human blood and urine. [...] In 11 of 37 probands ''N'',''N''-dimethyltryptamine was demonstrated in blood (...). In the urine 42.95 ± 8.6 μg of dimethyltryptamine/24 h were excreted. | bibcode = 1965Natur.206.1052F | s2cid = 4226040 | doi-access = free }}</ref> In an article published four months later, the method used in their study was strongly criticized, and the credibility of their results challenged.<ref name="pmid5860629">{{cite journal | vauthors = Siegel M | title = A sensitive method for the detection of ''N'',''N''-dimethylserotonin (bufotenin) in urine; failure to demonstrate its presence in the urine of schizophrenic and normal subjects | journal = Journal of Psychiatric Research | volume = 3 | issue = 3 | pages = 205–211 | date = October 1965 | pmid = 5860629 | doi = 10.1016/0022-3956(65)90030-0 }}</ref>

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.<ref name="pmid11232854">{{cite journal | vauthors = Barker SA, Littlefield-Chabaud MA, David C | title = Distribution of the hallucinogens ''N'',''N''-dimethyltryptamine and 5-methoxy-''N'',''N''-dimethyltryptamine in rat brain following intraperitoneal injection: application of a new solid-phase extraction LC-APcI-MS-MS-isotope dilution method | journal = Journal of Chromatography. B, Biomedical Sciences and Applications | volume = 751 | issue = 1 | pages = 37–47 | date = February 2001 | pmid = 11232854 | doi = 10.1016/S0378-4347(00)00442-4 }}</ref><ref name="pmid11763413">{{cite journal | vauthors = Forsström T, Tuominen J, Karkkäinen J | title = Determination of potentially hallucinogenic N-dimethylated indoleamines in human urine by HPLC/ESI-MS-MS | journal = Scandinavian Journal of Clinical and Laboratory Investigation | volume = 61 | issue = 7 | pages = 547–556 | year = 2001 | pmid = 11763413 | doi = 10.1080/003655101753218319 | s2cid = 218987277 }}</ref> Gas chromatography, preferably coupled to mass spectrometry (GC-MS), is considered a minimum requirement.<ref name="pmid11763413" /> A study published in 2005<ref name="pmid16095048" /> implements the most sensitive and selective method ever used to measure endogenous DMT:<ref name="pmid20523750">{{cite journal | vauthors = Shen HW, Jiang XL, Yu AM | title = Development of a LC-MS/MS method to analyze 5-methoxy-''N'',''N''-dimethyltryptamine and bufotenine, and application to pharmacokinetic study | journal = Bioanalysis | volume = 1 | issue = 1 | pages = 87–95 | date = April 2009 | pmid = 20523750 | pmc = 2879651 | doi = 10.4155/bio.09.7 }}</ref> liquid chromatography-tandem mass spectrometry with electrospray ionization (LC-ESI-MS/MS) allows for reaching limits of detection (LODs) 12 to 200 fold lower than those attained by the best methods employed in the 1970s. The data summarized in the table below are from studies conforming to the abovementioned requirements (abbreviations used: CSF = cerebrospinal fluid; LOD = limit of detection; ''n'' = number of samples; ng/L and ng/kg = nanograms (10−9 g) per litre, and nanograms per kilogram, respectively):

{| class="wikitable" style="margin: 1em auto 1em auto; width:70%;" |+ align="bottom" | '''DMT''' in body fluids and tissues ''(NB: units have been harmonized)'' ! style="vertical-align:middle; text-align:center; width:30px;" | Species ! style="vertical-align:middle; text-align:center; width:60px;" | Sample ! style="vertical-align:middle; text-align:center; width:400px;" | Results |- ! rowspan="8" style="vertical-align:top; text-align:center; width:30px;" | Human | style="vertical-align:middle; width:60px;" | Blood serum | style="vertical-align:middle; width:400px;" | < LOD (''n'' = 66)<ref name="pmid16095048" /> |- | style="vertical-align:middle; width:60px;" | Blood plasma | style="vertical-align:middle; width:400px;" | < LOD (''n'' = 71)<ref name="pmid16095048" />  ♦  < LOD (''n'' = 38); 1,000 & 10,600 ng/L (''n'' = 2)<ref name="pmid4517484">{{cite journal | vauthors = Wyatt RJ, Mandel LR, Ahn HS, Walker RW, Vanden Heuvel WJ | title = Gas chromatographic-mass spectrometric isotope dilution determination of ''N'',''N''-dimethyltryptamine concentrations in normals and psychiatric patients | journal = Psychopharmacologia | volume = 31 | issue = 3 | pages = 265–270 | date = July 1973 | pmid = 4517484 | doi = 10.1007/BF00422516 | s2cid = 42469897 }}</ref> |- | style="vertical-align:middle; width:60px;" | Whole blood | style="vertical-align:middle; width:400px;" | < LOD (''n'' = 20); 50-790 ng/L (''n'' = 20)<ref name="pmid803203">{{cite journal | vauthors = Angrist B, Gershon S, Sathananthan G, Walker RW, López-Ramos B, Mandel LR, Vandenheuvel WJ | title = Dimethyltryptamine levels in blood of schizophrenic patients and control subjects | journal = Psychopharmacology | volume = 47 | issue = 1 | pages = 29–32 | date = May 1976 | pmid = 803203 | doi = 10.1007/BF00428697 | s2cid = 5850801 }}</ref> |- | style="vertical-align:middle; width:60px;" | Urine | style="vertical-align:middle; width:400px;" | < 100 ng/L (''n'' = 9)<ref name="pmid16095048" />  ♦  < LOD (''n'' = 60); 160-540 ng/L (''n'' = 5)<ref name="pmid11763413" />  ♦  Detected in ''n'' = 10 by GC-MS<ref name="pmid271509">{{cite journal | vauthors = Oon MC, Rodnight R | title = A gas chromatographic procedure for determining N, N-dimethyltryptamine and N-monomethyltryptamine in urine using a nitrogen detector | journal = Biochemical Medicine | volume = 18 | issue = 3 | pages = 410–419 | date = December 1977 | pmid = 271509 | doi = 10.1016/0006-2944(77)90077-1 }}</ref> |- style="vertical-align:middle;" | style="width:60px;" | Feces | style="width:400px;" | < 50 ng/kg (n = 12); 130 ng/kg (''n'' = 1)<ref name="pmid16095048" /> |- style="vertical-align:middle;" | style="width:60px;" | Kidney | style="width:400px;" | 15 ng/kg (''n'' = 1)<ref name="pmid16095048" /> |- style="vertical-align:middle;" | style="width:60px;" | Lung | style="width:400px;" | 14 ng/kg (''n'' = 1)<ref name="pmid16095048" /> |- | style="vertical-align:middle; width:60px;" | Lumbar CSF | style="vertical-align:middle; width:400px;" | 100,370 ng/L (''n'' = 1); 2,330-7,210 ng/L (''n'' = 3); 350 & 850 ng/L (''n'' = 2)<ref name="pmid289421">{{cite journal | vauthors = Smythies JR, Morin RD, Brown GB | title = Identification of dimethyltryptamine and O-methylbufotenin in human cerebrospinal fluid by combined gas chromatography/mass spectrometry | journal = Biological Psychiatry | volume = 14 | issue = 3 | pages = 549–556 | date = June 1979 | pmid = 289421 }}</ref> |- ! rowspan="4" style="vertical-align:top; text-align:center; width:30px;" | Rat | style="vertical-align:middle; width:60px;" | Kidney | style="vertical-align:middle; width:400px;" | 12 & 16 ng/kg (''n'' = 2)<ref name="pmid16095048" /> |- style="vertical-align:middle;" | style="width:60px;" | Lung | style="width:400px;" | 22 & 12 ng/kg (''n'' = 2)<ref name="pmid16095048" /> |- style="vertical-align:middle;" | style="width:60px;" | Liver | style="width:400px;" | 6 & 10 ng/kg (''n'' = 2)<ref name="pmid16095048" /> |- | style="vertical-align:middle; width:60px;" | Brain | style="vertical-align:middle; width:400px;" | 10 & 15 ng/kg (''n'' = 2)<ref name="pmid16095048" />  ♦  Measured in synaptic vesicular fraction<ref name="pmid20877">{{cite journal | vauthors = Christian ST, Harrison R, Quayle E, Pagel J, Monti J | title = The in vitro identification of dimethyltryptamine (DMT) in mammalian brain and its characterization as a possible endogenous neuroregulatory agent | journal = Biochemical Medicine | volume = 18 | issue = 2 | pages = 164–183 | date = October 1977 | pmid = 20877 | doi = 10.1016/0006-2944(77)90088-6 }}</ref> |- ! style="vertical-align:middle; width:30px;" | Rabbit | style="vertical-align:middle; width:60px;" | Liver | style="vertical-align:middle; width:400px;" | < 10 ng/kg (''n'' = 1)<ref name="pmid16095048" /> |}

A 2013 study found DMT in microdialysate obtained from a rat's pineal gland, providing evidence of endogenous DMT in the mammalian brain.<ref name="pmid23881860" /> 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.<ref name = "Dean_2019" />

Quantities of dimethyltryptamine and ''O''-methylbufotenin were found present in the cerebrospinal fluid of humans in a 1978 psychiatric study.<ref>{{cite journal | vauthors = Corbett L, Christian ST, Morin RD, Benington F, Smythies JR | title = Hallucinogenic ''N''-methylated indolealkylamines in the cerebrospinal fluid of psychiatric and control populations | journal = The British Journal of Psychiatry | volume = 132 | issue = 2 | pages = 139–144 | date = February 1978 | pmid = 272218 | doi = 10.1192/bjp.132.2.139 | s2cid = 37144421 }}</ref>

===Biosynthesis=== class=skin-invert-image|thumb|left|Biosynthetic pathway for ''N'',''N''-dimethyltryptamine

Dimethyltryptamine is an indole alkaloid derived from the shikimate pathway. Its biosynthesis is relatively simple and summarized in the adjacent picture. In plants, the parent amino acid {{sc|L}}-tryptophan is produced endogenously where in animals {{sc|L}}-tryptophan is an essential amino acid coming from diet. No matter the source of {{sc|L}}-tryptophan, the biosynthesis begins with its decarboxylation by an aromatic amino acid decarboxylase (AADC) enzyme (step 1). The resulting decarboxylated tryptophan analogue is tryptamine. Tryptamine then undergoes a transmethylation (step 2): the enzyme indolethylamine-''N''-methyltransferase (INMT) catalyzes the transfer of a methyl group from cofactor ''S''-adenosylmethionine (SAM), via nucleophilic attack, to tryptamine. This reaction transforms SAM into ''S''-adenosylhomocysteine (SAH), and gives the intermediate product ''N''-methyltryptamine (NMT).<ref name="pmid13685339">{{cite journal | vauthors = Axelrod J | title = Enzymatic formation of psychotomimetic metabolites from normally occurring compounds | url = https://archive.org/details/sim_science_1961-08-04_134_3475/page/342 | journal = Science | volume = 134 | issue = 3475 | page = 343 | date = August 1961 | pmid = 13685339 | doi = 10.1126/science.134.3475.343 | bibcode = 1961Sci...134..343A | s2cid = 39122485 }}</ref><ref name="pmid779022">{{cite journal | vauthors = Rosengarten H, Friedhoff AJ | title = A review of recent studies of the biosynthesis and excretion of hallucinogens formed by methylation of neurotransmitters or related substances | journal = Schizophrenia Bulletin | volume = 2 | issue = 1 | pages = 90–105 | year = 1976 | pmid = 779022 | doi = 10.1093/schbul/2.1.90 | doi-access = free }}</ref> 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,<ref name="pmid6792104">{{cite book | vauthors = Barker SA, Monti JA, Christian ST | year = 1981 | chapter = N,N-Dimethyltryptamine: An Endogenous Hallucinogen | title = International Review of Neurobiology Volume 22 | volume = 22 | pages = 83–110 | isbn = 978-0-12-366822-6 | doi = 10.1016/S0074-7742(08)60291-3 | pmid = 6792104 }}</ref><ref name="pmid4756800">{{cite journal | vauthors = Lin RL, Narasimhachari N, Himwich HE | title = Inhibition of indolethylamine-''N''-methyltransferase by ''S''-adenosylhomocysteine | journal = Biochemical and Biophysical Research Communications | volume = 54 | issue = 2 | pages = 751–759 | date = September 1973 | pmid = 4756800 | doi = 10.1016/0006-291X(73)91487-3 | bibcode = 1973BBRC...54..751L }}</ref><ref name="pmid9852119">{{cite journal | vauthors = Thompson MA, Weinshilboum RM | title = Rabbit lung indolethylamine ''N''-methyltransferase. cDNA and gene cloning and characterization | journal = The Journal of Biological Chemistry | volume = 273 | issue = 51 | pages = 34502–34510 | date = December 1998 | pmid = 9852119 | doi = 10.1074/jbc.273.51.34502 | doi-access = free }}</ref> and DMT<ref name="pmid6792104" /><ref name="pmid9852119" /> were shown ''ex vivo'' to be among the most potent inhibitors of rabbit INMT activity.

This transmethylation mechanism has been repeatedly and consistently proven by radiolabeling of SAM methyl group with carbon-14 ((14C-CH3)SAM).<ref name="pmid13685339" /><ref name="pmid6792104" /><ref name="pmid9852119" /><ref name="pmid14361">{{cite journal | vauthors = Mandel LR, Prasad R, Lopez-Ramos B, Walker RW | title = The biosynthesis of dimethyltryptamine in vivo | journal = Research Communications in Chemical Pathology and Pharmacology | volume = 16 | issue = 1 | pages = 47–58 | date = January 1977 | pmid = 14361 }}</ref><ref name="pmid10552930">{{cite journal | vauthors = Thompson MA, Moon E, Kim UJ, Xu J, Siciliano MJ, Weinshilboum RM | title = Human indolethylamine ''N''-methyltransferase: cDNA cloning and expression, gene cloning, and chromosomal localization | journal = Genomics | volume = 61 | issue = 3 | pages = 285–297 | date = November 1999 | pmid = 10552930 | doi = 10.1006/geno.1999.5960 | url = http://crfdl.org:1111/xmlui/bitstream/handle/123456789/307/Thompson99humanINMT.pdf?sequence=1 | format = PDF }}{{dead link|date=March 2018 |bot=InternetArchiveBot |fix-attempted=yes }}</ref>

==History== {{See also|Ayahuasca#History}}

DMT derived from plant-based sources has been used as an entheogen in South America for thousands of years.<ref name="MillerAlbarracin-JordanMoore2019">{{cite journal | vauthors = Miller MJ, Albarracin-Jordan J, Moore C, Capriles JM | date = June 2019 | title = Chemical evidence for the use of multiple psychotropic plants in a 1,000-year-old ritual bundle from South America | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 116 | issue = 23 | pages = 11207–11212 | doi = 10.1073/pnas.1902174116 | doi-access = free | pmc = 6561276 | pmid = 31061128 | bibcode = 2019PNAS..11611207M }}</ref><ref name="Anwar2019">{{Cite web|url=https://news.berkeley.edu/2019/05/06/ayahuasca-sacred-bundle/|title=Ayahuasca fixings found in 1,000-year-old Andean sacred bundle|vauthors=Anwar Y|date=6 May 2019|website=Berkeley News|language=en-US|access-date=21 May 2019|archive-date=12 May 2019|archive-url=https://web.archive.org/web/20190512172214/https://news.berkeley.edu/2019/05/06/ayahuasca-sacred-bundle/|url-status=live}}</ref>

DMT was first synthesized in 1931 by Canadian chemist Richard Manske.<ref name="Shulgin1976" /><ref name="Manske R.H.F. 1931 592–600">{{cite journal|year=1931|title=A synthesis of the methyltryptamines and some derivatives|url=http://rparticle.web-p.cisti.nrc.ca/rparticle/AbstractTemplateServlet?calyLang=eng&journal=cjr&volume=5&year=&issue=5&msno=cjr31-097|journal=Canadian Journal of Research|volume=5|issue=5|pages=592–600|doi=10.1139/cjr31-097| vauthors = Manske RH |bibcode=1931CJRes...5..592M|url-access=subscription}}{{Dead link|date=July 2018 |bot=InternetArchiveBot |fix-attempted=yes }}</ref><ref name="bdmxab">{{cite journal|date=November 1977|title=DMT: the fifteen minute trip|url=http://jeremybigwood.net/JBsPUBS/DMT/|journal=Head|volume=2|issue=4|pages=56–61| vauthors = Bigwood J, Ott J |access-date=28 November 2010|archive-url=https://web.archive.org/web/20060127003553/http://jeremybigwood.net/JBsPUBS/DMT/|archive-date=27 January 2006}}</ref> In general, its discovery as a natural product is credited to Brazilian chemist and microbiologist Oswaldo Gonçalves de Lima, who isolated an alkaloid he named ''nigerina'' (nigerine) from the root bark of ''Mimosa tenuiflora'' in 1946.<ref name="bdmxab" /><ref name="Strassman2001" /><ref name="Ott1996">{{cite book | vauthors = Ott J | year = 1996 | title = Pharmacotheon: Entheogenic Drugs, Their Plant Sources and History | publisher = Natural Products | edition = 2nd, densified | isbn = 978-0-9614234-9-0 | author-link = Jonathan Ott | location = Kennewick, WA }}</ref> However, in a careful review of the case Jonathan Ott shows that the empirical formula for nigerine determined by Gonçalves de Lima, which notably contains an atom of oxygen, can match only a partial, "impure" or "contaminated" form of DMT.<ref name="Ott1998" /> 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.<ref name="Ott1998" /><ref>{{cite journal| vauthors = Pachter IJ, Zacharias DE, Ribeiro O |title=Indole alkaloids of ''Acer saccharinum'' (the silver maple), ''Dictyoloma incanescens'', ''Piptadenia colubrina'', and ''Mimosa hostilis'' |journal=Journal of Organic Chemistry |date=September 1959 |volume=24 |issue=9 |pages=1285–1287 |doi=10.1021/jo01091a032 |bibcode=1959JOrgC..24.1285P }}</ref> 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).<ref name="Ott1998" /><ref>{{cite journal | vauthors = Fish MS, Johnson NM, Horning EC |date=November 1955 |title=Piptadenia alkaloids. Indole bases of ''P. peregrina'' (L.) Benth. and related species |journal=Journal of the American Chemical Society |volume=72 |issue=22 |pages=5892–5895 |doi=10.1021/ja01627a034|bibcode=1955JAChS..77.5892F }}</ref> Since 1955, DMT has been found in a number of organisms: in at least fifty plant species belonging to ten families,<ref name="Ott1994">{{cite book | vauthors = Ott J | year = 1994 | title = Ayahuasca Analogues: Pangæan Entheogens | publisher = Natural Products | edition = 1st | pages = 81–83 | isbn = 978-0-9614234-5-2 | location = Kennewick, WA, USA | oclc = 32895480 | author-link = Jonathan Ott }}</ref> and in at least four animal species, including one gorgonian<ref name="ReferenceA">{{cite journal|year=1978|title=Chemistry of Mediterranean gorgonians: simple indole derivatives from ''Paramuricea chamaeleon''|journal=Comparative Biochemistry and Physiology C|volume=61|issue=2|pages=361–362|doi=10.1016/0306-4492(78)90070-9| vauthors = Cimino G, De Stefano S }}</ref> and three mammalian species (including humans).{{citation needed|date=October 2022}}

In terms of a scientific understanding, the hallucinogenic effects of DMT were not uncovered until 1956 by Hungarian chemist and psychiatrist Stephen Szára.<ref name="Shulgin1976" /><ref name="Szara1956" /> Szára, who later worked for the United States National Institutes of Health, researched DMT after his order to acquire LSD from the Swiss company Sandoz Laboratories was rejected on the grounds that the powerful psychotropic could be dangerous in the hands of a communist country.<ref name="Strassman2001">{{cite book | vauthors = Strassman RJ | year = 2001 | title = DMT: The Spirit Molecule. A Doctor's Revolutionary Research into the Biology of Near-Death and Mystical Experiences | publisher = Park Street | isbn = 978-0-89281-927-0 | url = https://archive.org/details/dmtspiritmolecul00rick | location = Rochester, VT | author-link = Rick Strassman }} ({{cite web | date = 2015-08-01 | title = Chapter summaries | website = Rick Strassman MD | url = http://rickstrassman.com/index.php?option=com_content&view=article&id=61&Itemid=60 | access-date = 27 February 2012 | archive-date = 16 May 2016 | archive-url = https://web.archive.org/web/20160516020600/https://www.rickstrassman.com/index.php?id=61&itemid=60&option=com_content&view=article | url-status = live }})</ref> 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 Speeter–Anthony route, which was then administered to 20{{nbsp}}volunteers by intramuscular injection. Urine samples were collected from these volunteers for the identification of DMT metabolites.<ref name="Szara1956">{{cite journal | vauthors = Szara S | title = Dimethyltryptamin: its metabolism in man; the relation to its psychotic effect to the serotonin metabolism | journal = Experientia | volume = 12 | issue = 11 | pages = 441–442 | date = November 1956 | pmid = 13384414 | doi = 10.1007/bf02157378 | s2cid = 7775625 }}</ref> This is considered to be the link between the chemical structure of DMT and its cultural consumption as a psychoactive and religious sacrament.<ref name="McKennaCallawayGrob1998">{{cite journal | vauthors = McKenna DJ, Callaway JC, Grob CS | year = 1998 | title = The scientific investigation of Ayahuasca: a review of past and current research | journal = The Heffter Review of Psychedelic Research | volume = 1 | issue = 65–77| pages = 195–223 }}</ref>

Another historical milestone was the discovery of DMT in plants frequently used by Amazonian natives as additive to the vine ''Banisteriopsis caapi'' to make ayahuasca decoctions. In 1957, American chemists Francis Hochstein and Anita Paradies identified DMT in an "aqueous extract" of leaves of a plant they named ''Prestonia amazonicum'' [''sic''] and described as "commonly mixed" with ''B. caapi''.<ref>{{cite journal | vauthors = Hochstein FA, Paradies AM |year=1957 |title=Alkaloids of ''Banisteria caapi'' and ''Prestonia amazonicum'' |journal=Journal of the American Chemical Society |volume=79 |issue=21 |pages=5735–5736 |doi=10.1021/ja01578a041 |bibcode=1957JAChS..79.5735H }}</ref> The lack of a proper botanical identification of ''Prestonia amazonica'' in this study led American ethnobotanist Richard Evans Schultes (1915–2001) and other scientists to raise serious doubts about the claimed plant identity.<ref>{{cite journal |vauthors=Schultes RE, Raffauf RF |year=1960 |title=''Prestonia'': An Amazon narcotic or not? |journal=Botanical Museum Leaflets, Harvard University |volume=19 |issue=5 |pages=109–122 |doi=10.5962/p.168526 |s2cid=91123988 |issn=0006-8098 |url=https://www.biodiversitylibrary.org/item/31906#page/126/mode/1up |doi-access=free |access-date=2018-01-14 |archive-date=2018-08-10 |archive-url=https://web.archive.org/web/20180810224847/https://www.biodiversitylibrary.org/item/31906#page/126/mode/1up |url-status=live }}</ref><ref name="pmid14337385">{{cite journal | vauthors = Poisson J | title = Note on "Natem", A Toxic Peruvian Beverage, and ITS Alkaloids | language = fr | journal = Annales Pharmaceutiques Francaises | volume = 23 | pages = 241–244 | date = April 1965 | pmid = 14337385 | trans-title = Note on "Natem", a toxic Peruvian beverage, and its alkaloids }}</ref> The mistake likely led the writer William Burroughs to regard the DMT he experimented with in Tangier in 1961 as "Prestonia".{{sfn|St John|2015|page=29}} 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'').<ref name="pmid14337385" /> Published in 1970, the first identification of DMT in the plant ''Psychotria viridis'',<ref name="Ott1996" /> another common additive of ayahuasca, was made by a team of American researchers led by pharmacologist Ara der Marderosian.<ref>{{cite journal | vauthors = Der Marderosian AH, Kensinger KM, Chao JM, Goldstein FJ |year=1970 |title=The use and hallucinatory principles of a psychoactive beverage of the Cashinahua tribe (Amazon basin) |journal=Drug Dependence |volume=5 |pages=7–14 |issn=0070-7368 |oclc=1566975}}</ref> Not only did they detect DMT in leaves of ''P. viridis'' obtained from Kaxinawá indigenous people, but they were also the first to identify it in a sample of an ayahuasca decoction, prepared by the same indigenous people.<ref name="Ott1996" />

In the 1960s, DMT was known as a "businessman's trip" in the United States because of its very rapid onset and short duration when smoked.<ref name="HarozGreenberg2005" />

==Society and culture== ===Popular culture=== In the 2022 Australian film ''Everything in Between'', the lead character smokes what is implied to be DMT in the opening sequence, which is followed by hallucination-like visual effects and an altered state of consciousness.<ref>{{cite web | author = HEAVY Staff | date = 17 October 2022 | title = Everything in Between – HEAVY Cinema review | website = HEAVY Cinema | url = https://cinema.heavymag.com.au/everything-in-between-review/ | access-date = 30 July 2025 }}</ref>

===Cantelmoism=== A man named Chris Cantelmo attempted to create an online cult around DMT called "Cantelmoism" in the late 2010s.<ref name="Thompson2022">{{cite web | vauthors = Thompson N | date = 27 April 2022 | title = How One Man Tried to Build a DMT-Based Cult on Reddit and Lost Everything | website = VICE | publisher = VICE | url = https://www.vice.com/en/article/how-one-man-tried-to-build-a-dmt-based-cult-on-reddit-and-lost-everything/ | access-date = 25 March 2026 }}</ref> He was a wealthy biochemist and Yale University graduate who had worked in the pharmaceutical industry for several decades, including running multiple high-performance liquid chromatography (HPLC) companies.<ref name="Thompson2022" /> Cantelmo began his DMT cult endeavor on Reddit and other social media websites after trying DMT in 2018.<ref name="Thompson2022" /> He rapidly spent his wealth in a fervent attempt to promote DMT and get as many people to try it as possible, forming a cult in the process and becoming an online spectacle.<ref name="Thompson2022" /> Among other claims, Cantelmo asserted that DMT cured his brain cancer and that it would cure all other diseases.<ref name="Thompson2022" /> However, he later admitted that he had never had brain cancer and that it had really cured his "severe" lifelong atheism, which he likened to cancer.<ref name="Thompson2022" /> Cantelmo suffered from mental health issues and died of suicide whilst under pressure of losing his home in November 2019.<ref name="Thompson2022" />

===Black market=== Electronic cigarette cartridges or vape pens filled with DMT started to be sold on the black market by 2018.<ref name="Black2018">{{cite news | vauthors = Black L | title = New on the Black Market: Vape Pens Full of DMT | work = The Stranger | url = https://www.thestranger.com/features/2018/08/15/30763161/new-on-the-black-market-vape-pens-full-of-dmt | access-date = 2020-02-29 | archive-date = 2020-02-29 | archive-url = https://web.archive.org/web/20200229091407/https://www.thestranger.com/features/2018/08/15/30763161/new-on-the-black-market-vape-pens-full-of-dmt | url-status = live }}</ref><ref name="Power2020" /><ref name="McClure2020">{{cite web | vauthors = McClure J | title=DMT Pens: Is It Safe to Vape DMT? | website=DoubleBlind Mag | date=5 February 2020 | url=https://doubleblindmag.com/are-dmt-vape-pens-safe/ | access-date=15 March 2025}}</ref>

Akasha Song previously manufactured and sold DMT on the dark web and is said to have been the largest DMT producer and seller in history.<ref name="Greenberg2025">{{cite magazine | vauthors = Greenberg A | date = 22 May 2025 | title = The Epic Rise and Fall of a Dark-Web Psychedelics Kingpin | magazine = WIRED | url = https://www.wired.com/story/rise-fall-dark-web-psychedelics-kingpin-dmt/ | archive-date = 22 May 2025 | archive-url = https://archive.today/20250522102521/https://www.wired.com/story/rise-fall-dark-web-psychedelics-kingpin-dmt/ }}</ref>

===Legal status=== ====International law==== {{Main|Convention on Psychotropic Substances}}

Internationally, DMT is illegal to possess without authorisation, exemption or license, 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 continent and country==== {{See also|Legal status of ayahuasca by country}} In some countries, ayahuasca is a forbidden or controlled or regulated substance, while in other countries it is not a controlled substance or its production, consumption, and sale, is allowed to various degrees.

=====Asia===== * Israel - DMT is an illegal substance; production, trade, and possession are prosecuted as crimes.<ref name="judge">{{cite news |date=6 August 2013 |title=Judge's son arrested for importing 2kg of hallucinogenic drug |url=http://www.ynetnews.com/articles/0,7340,L-4414356,00.html |url-status=live |archive-url=https://web.archive.org/web/20170812064720/http://www.ynetnews.com/articles/0,7340,L-4414356,00.html |archive-date=12 August 2017 |access-date=11 August 2017 |work=Ynetnews |publisher=Yediot Ahronot |location=Tel Aviv |quote=Son of central district judge arrested for allegedly importing DMT – LSD like drug – from Holland. [...] The suspect denies the allegations against him and claims he did not know the substance was on the list of illegal drugs. |vauthors=Senyor E}}</ref> * India - DMT is illegal to produce, transport, trade in, or possess with a minimum prison or jail punishment of ten years.<ref>{{cite web | author = Mangalore Today, Mangalore | title = The GOD DRUG- DMT | website = Mangaloretoday.com | url = https://www.mangaloretoday.com/opinion/THE-GOD-DRUG-DMT.html | access-date = 10 August 2020 | archive-date = 21 September 2020 | archive-url = https://web.archive.org/web/20200921184859/http://www.mangaloretoday.com/opinion/THE-GOD-DRUG-DMT.html | url-status = live }}</ref>

=====Europe===== * Belgium - DMT cannot be possessed, sold, purchased or imported. Usage is not specifically prohibited, but since usage implies possession one could be prosecuted that way.<ref>{{cite web | date = 2023-03-08 | title = Wetgeving rond LSD en tripmiddelen | website = Druglijn.be | url = https://www.druglijn.be/drugs-abc/lsd-en-tripmiddelen/wetgeving | access-date = 2019-04-20 | archive-date = 2019-04-20 | archive-url = https://web.archive.org/web/20190420154514/https://www.druglijn.be/drugs-abc/lsd-en-tripmiddelen/wetgeving | url-status = live }}</ref> * France - DMT, along with most of its plant-sources, is classified as a ''stupéfiant'' (narcotic). * Germany - DMT is prohibited as a class I drug.<ref>{{cite web |title=Gesetz über den Verkehr mit Betäubungsmitteln (Betäubungsmittelgesetz – BtMG) Anlage I (zu § 1 Abs. 1) (nicht verkehrsfähige Betäubungsmittel) |url=https://www.gesetze-im-internet.de/btmg_1981/anlage_i.html |url-status=live |archive-url=https://web.archive.org/web/20150402113610/https://www.gesetze-im-internet.de/btmg_1981/anlage_i.html |archive-date=2015-04-02 |access-date=2018-08-25 |website=gesetze-im-internet.de}}</ref> *Ireland - DMT is an illegal Schedule 1 drug under the Misuse of Drugs Acts.<ref>{{cite web | author = Noel Baker | date = 8 September 2017 | title = Man fined for having drug used in Amazon | website = Irishexaminer.com | url = https://www.irishexaminer.com/ireland/man-fined-for-having-drug-used-in-amazon-458558.html | access-date = 28 January 2019 | archive-date = 29 January 2019 | archive-url = https://web.archive.org/web/20190129064142/https://www.irishexaminer.com/ireland/man-fined-for-having-drug-used-in-amazon-458558.html | url-status = live }}</ref> An attempt in 2014 by a member of the Santo Daime church to gain a religious exemption to import the drug failed.<ref>{{cite web |date=4 December 2017 |title=Sect leader spared jail for importing hallucinogenic drug for religious 'sacrament' |url=https://www.independent.ie/irish-news/courts/sect-leader-spared-jail-for-importing-hallucinogenic-drug-for-religious-sacrament-36377897.html |url-status=live |archive-url=https://web.archive.org/web/20190129124337/https://www.independent.ie/irish-news/courts/sect-leader-spared-jail-for-importing-hallucinogenic-drug-for-religious-sacrament-36377897.html |archive-date=29 January 2019 |access-date=28 January 2019 |website=Independent.ie}}</ref> * Latvia - DMT is prohibited as a Schedule I drug.<ref>{{cite web |title=Noteikumi par Latvijā kontrolējamajām narkotiskajām vielām, psihotropajām vielām un prekursoriem |url=https://likumi.lv/ta/id/121086-noteikumi-par-latvija-kontrolejamajam-narkotiskajam-vielam-psihotropajam-vielam-un-prekursoriem#piel1 |url-status=live |archive-url=https://web.archive.org/web/20190213123947/https://likumi.lv/ta/id/121086-noteikumi-par-latvija-kontrolejamajam-narkotiskajam-vielam-psihotropajam-vielam-un-prekursoriem#piel1 |archive-date=13 February 2019 |access-date=13 February 2019 |website=Likumi.lv}}</ref><ref>{{cite web |title=Regulations Regarding Narcotic Substances, Psychotropic Substances and Precursors to be Controlled in Latvia |url=https://likumi.lv/ta/en/en/id/121086 |url-status=live |archive-url=https://web.archive.org/web/20190213124007/https://likumi.lv/ta/en/en/id/121086 |archive-date=13 February 2019 |access-date=13 February 2019 |website=likumi.lv}}</ref> * Netherlands - The drug is banned as it is classified as a List 1 Drug per the Opium Law. Production, trade and possession of DMT are prohibited. * Serbia - DMT, along with stereoisomers and salts is classified as List 4 (Psychotropic substances) substance according to Act on Control of Psychoactive Substances. * Sweden - DMT is considered a Schedule 1 drug. The Swedish supreme court concluded in 2018 that possession of processed plant material containing a significant amount of DMT is illegal. However, possession of unprocessed such plant material was ruled legal.<ref>{{cite web |title=Läkemedelsverkets författningssamling |url=https://lakemedelsverket.se/upload/lvfs/LVFS_2011-10.pdf |archive-url=https://web.archive.org/web/20180412145222/https://lakemedelsverket.se/upload/lvfs/LVFS_2011-10.pdf |archive-date=12 April 2018 |access-date=22 July 2019}}</ref><ref>{{cite web |title=HÖGSTA DOMSTOLENS DOM Mål nr meddelad i Stockholm den 13 December 2018 |url=https://www.domstol.se/globalassets/filer/domstol/hogstadomstolen/avgoranden/20182/b-1605-18.pdf |url-status=live |archive-url=https://web.archive.org/web/20200309130030/https://www.domstol.se/globalassets/filer/domstol/hogstadomstolen/avgoranden/20182/b-1605-18.pdf |archive-date=2020-03-09 |access-date=8 March 2022 |website=Domstol.se}}</ref> * United Kingdom - DMT is classified as a Class A drug.

=====North America===== * Canada - DMT is classified as a Schedule III drug under the Controlled Drugs and Substances Act, but is legal for religious groups to use.<ref>{{Cite web |date=8 May 2019 |title=Health Canada allows more religious groups to import psychedelic ayahuasca |url=https://www.ctvnews.ca/health/article/health-canada-allows-more-religious-groups-to-import-psychedelic-ayahuasca/ |url-status=live |archive-url=https://web.archive.org/web/20220421212418/https://www.ctvnews.ca/health/health-canada-allows-more-religious-groups-to-import-psychedelic-ayahuasca-1.4414145 |archive-date=21 April 2022 |access-date=8 March 2022 |website=Ctvnews.ca |vauthors=O'Brien C}}</ref> In 2017 the Santo Daime Church Céu do Montréal received religious exemption to use ayahuasca as a sacrament in their rituals.<ref>{{Cite news | vauthors = Dunlevy TC |date=15 October 2019 |title=What's all the buzz about? Montreal woman seeks to demystify ayahuasca. |url=https://www.montrealgazette.com/opinion/columnists/article400780.html |url-status=live |archive-url=https://web.archive.org/web/20250422092750/https://www.montrealgazette.com/opinion/columnists/article400780.html |archive-date=April 22, 2025 |work=Montreal Gazette}}</ref> * United States - DMT is classified in the United States as a Schedule I drug under the Controlled Substances Act of 1970. In 2019, it was decriminalized, along with other naturally derived psychedelics, in the city of Oakland after a campaign by Decriminalize Nature.<ref>{{cite magazine | vauthors = Blistein J | date = June 5, 2019 | title = Oakland Decriminalizes Magic Mushrooms, Other Natural Psychedelics | magazine = Rolling Stone | url = https://www.rollingstone.com/culture/culture-news/oakland-decriminalize-magic-mushrooms-natural-psychedelics-844879/ | access-date = December 16, 2025 | archive-date = August 28, 2025 | archive-url = https://web.archive.org/web/20250828211825/https://www.rollingstone.com/culture/culture-news/oakland-decriminalize-magic-mushrooms-natural-psychedelics-844879/ | location = | url-status = live }}</ref>

=====Other===== * Russia - Classified as a Schedule I narcotic, including its derivatives (see sumatriptan and zolmitriptan).<ref>{{cite web |title=Постановление Правительства РФ от 30 June 1998 N 681 "Об утверждении перечня наркотических средств, психотропных веществ и их прекурсоров, подлежащих контролю в Российской Федерации" (с изменениями и дополнениями) |url=http://base.garant.ru/12112176/ |url-status=live |archive-url=https://web.archive.org/web/20130420064645/http://base.garant.ru/12112176/ |archive-date=20 April 2013 |access-date=5 December 2016 |website=Base.garant.ru}}</ref>

=====Oceania===== * New Zealand - DMT is classified as a Class A drug under the Misuse of Drugs Act 1975.<ref>{{cite news |author-link2=New Zealand Press Association |date=19 May 2011 |title=Rare drug bound for Blenheim |url=http://www.stuff.co.nz/marlborough-express/news/5025678/Rare-drug-bound-for-Blenheim |url-status=live |archive-url=https://web.archive.org/web/20121024072226/http://www.stuff.co.nz/marlborough-express/news/5025678/Rare-drug-bound-for-Blenheim |archive-date=24 October 2012 |access-date=23 May 2012 |newspaper=Marlborough Express |publisher=Fairfax New Zealand |location=Blenheim, New Zealand |vauthors=Berry M, ((NZPA))}}</ref><ref name="NZMoDA">{{cite web |date=1 May 2012 |title=Schedule 1: Class A controlled drugs |url=http://www.legislation.govt.nz/act/public/1975/0116/latest/DLM436576.html |url-status=live |archive-url=https://web.archive.org/web/20120302164159/http://legislation.govt.nz/act/public/1975/0116/latest/DLM436576.html |archive-date=2 March 2012 |access-date=23 May 2012 |website=Misuse of Drugs Act 1975 |publisher=Parliamentary Counsel Office/Te Tari Tohutohu Pāremata |ref=NZMoDA |location=Wellington, N.Z.}}</ref> * Australia - DMT is listed as a Schedule 9 prohibited substance in Australia under the Poisons Standard (October 2015).<ref name="Poisons Standard">{{cite web | author = Health, Disability and Ageing | date = 30 September 2015 | title = Poisons Standard October 2015 | work = comlaw.gov.au | publisher = Office Parliamentary Counsel | url = https://www.comlaw.gov.au/Details/F2015L01534 | access-date = 2016-01-06 | archive-date = 2016-01-19 | archive-url = https://web.archive.org/web/20160119074606/https://www.comlaw.gov.au/Details/F2015L01534/ | url-status = live }}</ref> A Schedule 9 drug is outlined in the Poisons Act 1964 as "Substances which may be abused or misused, the manufacture, possession, sale, or use of which should be prohibited by law except when required for medical or scientific research, or for analytical, teaching or training purposes with approval of the CEO".<ref>{{cite web |date=1964 |title=Poisons Act |url=http://www.slp.wa.gov.au/pco/prod/FileStore.nsf/Documents/MRDocument:26063P/$FILE/Poisons%20Act%201964%20-%20%5B09-f0-04%5D.pdf?OpenElement |archive-url=https://web.archive.org/web/20151222191725/http://www.slp.wa.gov.au/pco/prod/FileStore.nsf/Documents/MRDocument%3A26063P/%24FILE/Poisons%20Act%201964%20-%20%5B09-f0-04%5D.pdf?OpenElement |archive-date=22 December 2015 |work=slp.wa.gov.au}}</ref> Between 2011 and 2012, the Australian federal government was considering changes to the Australian Criminal Code that would classify any plants containing any amount of DMT as "controlled plants".<ref>{{cite web |date=24 June 2010 |title=Consultation on implementation of model drug schedules for Commonwealth serious drug offenses |url=http://www.ag.gov.au/www/agd/agd.nsf/Page/Consultationsreformsandreviews_ConsultationonimplementationofmodeldrugschedulesforCommonwealthseriousdrugoffences |archive-url=https://web.archive.org/web/20111107074102/http://www.ag.gov.au/www/agd/agd.nsf/Page/Consultationsreformsandreviews_ConsultationonimplementationofmodeldrugschedulesforCommonwealthseriousdrugoffences |archive-date=7 November 2011 |publisher=Australian Government, Attorney-General's Department}}</ref> DMT itself was already controlled under current laws. The proposed changes included other similar blanket bans for other substances, such as a ban on any and all plants containing mescaline or ephedrine. The proposal was not pursued after political embarrassment on realisation that this would make the official floral emblem of Australia, Acacia pycnantha (golden wattle), illegal.{{citation needed|date=January 2021}} 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).<ref>{{cite journal | date = August 2012 | title = Aussie DMT BAN | journal = American Herb Association Quarterly Newsletter | volume = 27 | issue = 3 | page = 14 | url = http://connection.ebscohost.com/c/articles/79564875/aussie-dmt-ban | archive-date = 16 December 2014 | archive-url = https://web.archive.org/web/20141216060822/http://connection.ebscohost.com/c/articles/79564875/aussie-dmt-ban }}</ref> Under the Misuse of Drugs Act 1981 6.0g (3/16oz) of DMT is considered enough to determine a court of trial and 2.0g (1/16oz) is considered intent to sell and supply.<ref>{{cite web |title=Misuse of Drugs Act 1981 (2015) |url=http://www.slp.wa.gov.au/pco/prod/FileStore.nsf/Documents/MRDocument:28280P/$FILE/Misuse%20Of%20Drugs%20Act%201981%20-%20%5B06-e0-00%5D.pdf?OpenElement |archive-url=https://web.archive.org/web/20151222180141/http://www.slp.wa.gov.au/pco/prod/FileStore.nsf/Documents/MRDocument%3A28280P/%24FILE/Misuse%20Of%20Drugs%20Act%201981%20-%20%5B06-e0-00%5D.pdf?OpenElement |archive-date=22 December 2015 |work=slp.wa.gov.au}}</ref>

In December 2004, the U.S. Supreme Court lifted a stay allowing the Brazil-based União do Vegetal church to use a decoction containing DMT in their Christmas services that year. This decoction is a tea made from boiled leaves and vines, known as hoasca within the UDV, and ayahuasca in different cultures. In ''Gonzales v. O Centro Espírita Beneficente União do Vegetal'', the Supreme Court heard arguments on November 1, 2005, and unanimously ruled in February 2006 that the U.S. federal government must allow the UDV to import and consume the tea for religious ceremonies under the 1993 Religious Freedom Restoration Act.

Also suing under the Religious Freedom Restoration Act, three Santo Daime churches filed suit in federal court to gain legal status to import DMT-containing ayahuasca tea in 2008. The U.S. District Court in Oregon ruled in ''Church of the Holy Light of the Queen v. Mukasey'' (615 F.Supp.2d 1210) ruled that the religious group could import, distribute, and brew ayahuasca. A matter of religious freedom protected by the religious freedom law, the court issued a permanent injunction barring the government from prohibiting or penalizing the sacramental use of the religious drink.

==Research== ===Depression=== {{See also|List of investigational hallucinogens and entactogens}}

Short-acting psychedelics like DMT and 5-MeO-DMT show rapid and sustained antidepressant effects in treatment-resistant depression, potentially offering a more scalable alternative to psilocybin, though larger controlled trials are needed to confirm efficacy.<ref name="Ramaekers2025">{{cite journal |vauthors=Ramaekers JG |date=May 2025 |title=Less is more? Antidepressant effects of short-acting psychedelics |journal=Neuropsychopharmacology |volume=50 |issue=6 |pages=875–876 |doi=10.1038/s41386-025-02103-5 |pmc=12032289 |pmid=40258989 }}</ref><ref name="RamaekersReckwegMason2025">{{cite journal |vauthors=Ramaekers JG, Reckweg JT, Mason NL |date=January 2025 |title=Benefits and Challenges of Ultra-Fast, Short-Acting Psychedelics in the Treatment of Depression |url=https://cris.maastrichtuniversity.nl/en/publications/fb3d3cba-472c-42bf-b665-bf9607461199 |journal=The American Journal of Psychiatry |volume=182 |issue=1 |pages=33–46 |doi=10.1176/appi.ajp.20230890 |pmid=39741439}}</ref>

A recent Phase 1/2 clinical trial evaluated the safety, tolerability, pharmacokinetics, and antidepressant effects of SPL026, an intravenous formulation of DMT fumarate, in both healthy volunteers and patients with moderate-to-severe major depressive disorder, using randomized, placebo-controlled and open-label dosing protocols.<ref>{{ClinicalTrialsGov|NCT04673383|A Double-blind, Randomised, Placebo-controlled Study of Intravenous Doses of SPL026 (DMT Fumarate), a Serotonergic Psychedelic, in Healthy Subjects (Part A) and Patients With Major Depressive Disorder (Part B) }}</ref> It found that inhaled 5-MeO-DMT (GH001) was well tolerated and produced rapid antidepressant effects in treatment-resistant depression, with individualized dosing showing the highest remission rates.<ref>{{cite journal | vauthors = James E, Erritzoe D, Benway T, Joel Z, Timmermann C, Good M, Agnorelli C, Weiss BM, Barba T, Campbell G, Baker Jones M, Hughes C, Topping H, Boyce M, Routledge C | title = Safety, tolerability, pharmacodynamic and wellbeing effects of SPL026 (dimethyltryptamine fumarate) in healthy participants: a randomized, placebo-controlled phase 1 trial | journal = Frontiers in Psychiatry | volume = 14 | article-number = 1305796 | date = 2023 | pmid = 38274414 | pmc = 10810248 | doi = 10.3389/fpsyt.2023.1305796 | doi-access = free }}</ref>

A Phase 1 open-label study assessed the safety, tolerability, pharmacokinetics, and preliminary efficacy of intravenous SPL026 alone or combined with SSRIs in patients with major depressive disorder whose symptoms were not fully relieved by SSRIs.<ref>{{ClinicalTrialsGov|NCT05553691|An Open-Label Study Investigating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics & Exploratory Efficacy of Intravenous SPL026 Drug Product (DMT Fumarate) Alone or in Combination With SSRIs in Patients With Major Depressive Disorder}}</ref>

In a Phase 2a open-label trial, inhaled DMT produced rapid, well-tolerated, and sustained antidepressant effects in patients with treatment-resistant depression, showing high response and remission rates within 7 days and lasting up to 3 months.<ref name="Falchi-CarvalhoPalhano-FontesWießner2025">{{cite journal | vauthors = Falchi-Carvalho M, Barros H, Bolcont R, Laborde S, Wießner I, ((Ruschi B Silva S)), Montanini D, Barbosa DC, Teixeira E, Florence-Vilela R, Almeida R, de Macedo RK, Arichelle F, Pantrigo ÉJ, Costa-Macedo JV, Arcoverde E, Galvão-Coelho N, Araujo DB, Palhano-Fontes F | title = Rapid and sustained antidepressant effects of vaporized N,N-dimethyltryptamine: a phase 2a clinical trial in treatment-resistant depression | journal = Neuropsychopharmacology | volume = 50 | issue = 6 | pages = 895–903 | date = May 2025 | pmid = 40258990 | doi = 10.1038/s41386-025-02091-6 | pmc = 12032144 }}</ref>

A single-day, open-label trial found that vaporized DMT produced rapid and sustained antidepressant effects in treatment-resistant depression, with up to 50% of participants maintaining remission one month post-dose.<ref name="Falchi-CarvalhoBarrosBolcont2025">{{cite journal | vauthors = Falchi-Carvalho M, Barros H, Bolcont R, Laborde S, Wießner I, ((Ruschi B. Silva S)), Montanini D, Barbosa DC, Teixeira E, Florence-Vilela R, Almeida R | title = The Antidepressant Effects of Vaporized ''N'',''N''-Dimethyltryptamine: An Open-Label Pilot Trial in Treatment-Resistant Depression | journal = Psychedelic Medicine | volume = 3 | issue = 1 | pages = 48–52 | date = March 2025 | pmid = 40337754 | pmc = 12054606 | doi = 10.1089/psymed.2024.0002 |ref=CITEREFFalchi-CarvalhoBarrosBolcontLaborde2025March}}</ref>

There are completed and ongoing trials of VLS-01, a buccal film formulation of DMT, in treating patients with treatment-resistant depression. In a completed Phase 1 trial, this formulation was found to be well tolerated, with adverse effects being mild or moderate.<ref>{{cite web | vauthors = Kuntz L | date = 2026-04-25 | title = VLS-01 for Treatment-Resistant Depression: Positive Phase1B Results {{!}} Psychiatric Times | website = www.psychiatrictimes.com | url = https://www.psychiatrictimes.com/view/vls-01-for-treatment-resistant-depression-positive-phase1b-results | access-date = 2026-04-25 }}</ref> As of April 2026, there are phase 2 trials ongoing in the United States and Australia.<ref>{{cite web | date = 2024-07-24 | title = VLS-01-203 BU in Treatment Resistant Depression - Clinical Trials Registry - ICH GCP | website = ichgcp.net | url = https://ichgcp.net/clinical-trials-registry/NCT06524830 | access-date = 2026-04-25 }}</ref><ref>{{Cite web |title=ANZCTR - Registration |url=https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=24321&isClinicalTrial=True |access-date=2026-04-25 |website=anzctr.org.au}}</ref><ref>{{cite report | vauthors = atai Therapeutics I | date = 2026-02-03 | title = A Phase 2, Multicenter, Double-blind, Randomized, Placebo-controlled Trial to Assess the Efficacy, Safety, and Tolerability of Repeated Doses of VLS-01 Buccal Film in Participants With Treatment Resistant Depression | publisher = clinicaltrials.gov | issue = NCT06524830 | url = https://clinicaltrials.gov/study/NCT06524830 }}</ref>

===Endogenous role=== DMT exists naturally in humans and other animals; it may play significant roles in mammalian physiology—potentially as a neurotransmitter, hormone, and immunomodulator—despite longstanding skepticism based on outdated or flawed evidence.<ref name="JiménezBouso2022" />

== References == {{Reflist}}

== External links == {{Commons category|Dimethyltryptamine}} * [https://isomerdesign.com/pihkal/explore/5006 DMT - Isomer Design] * [https://psychonautwiki.org/wiki/DMT DMT - PsychonautWiki] * [https://www.erowid.org/chemicals/dmt/dmt.shtml DMT - Erowid] * [https://erowid.org/library/books_online/tihkal/tihkal06.shtml DMT - TiHKAL - Erowid] * [https://isomerdesign.com/pihkal/read/tk/6 DMT - TiHKAL - Isomer Design]

{{Psychedelics}} {{Neurotransmitters}} {{Serotonin receptor modulators}} {{Monoamine releasing agents}} {{Sigma receptor modulators}} {{Tryptamines}}

Category:5-HT1A agonists Category:5-HT2A agonists Category:5-HT2B agonists Category:5-HT2C agonists Category:Ayahuasca Category:Biased ligands Category:Dimethylamino compounds Category:Dimethyltryptamine Category:Entheogens Category:Experimental antidepressants Category:Experimental anxiolytics Category:Experimental hallucinogens Category:N,N-Dialkyltryptamines Category:Partial monoamine releasing agents Category:Psychedelic tryptamines Category:Psychoplastogens Category:Serotonin receptor agonists Category:Serotonin releasing agents Category:Sigma agonists Category:TiHKAL Category:Tryptamine alkaloids