Editing N,N-Dimethyltryptamine (section)

===Pharmacokinetics===
Closely coextending with peak psychedelic effects, the mean time to reach peak concentration (''T''<sub>max</sub>) has been determined to be 10–15 minutes in whole blood after IM injection,<ref name="pmid4607811" /> and 2 minutes in plasma after IV administration.<ref name="pmid8297216" /> The half life after IV injection is 9-12 minutes.<ref name="pharmk">{{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> When taken orally mixed in an [[ayahuasca]] [[decoction]] or in [[Freeze-drying|freeze-dried]] ayahuasca [[Capsule (pharmacy)#Two-piece gel encapsulation|gel caps]], DMT ''T''<sub>max</sub> is considerably delayed to 107.59&nbsp;±&nbsp;32.5 minutes,<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 | 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 90–120 minutes,<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="McKennaTowers1984"/>

DMT peak level concentrations (''C''<sub>max</sub>) 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 (IV) 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 concentration]]s 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. However, 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 = <sup>11</sup>C-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''-[<sup>11</sup>C]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&nbsp;μmol/L range.<ref name="pmid20723248">{{cite journal | vauthors = Best J, Nijhout HF, Reed M | title = Serotonin synthesis, release and reuptake in terminals: a mathematical model | journal = Theoretical Biology & Medical Modelling | volume = 7 | issue = 1 | page = 34 | date = August 2010 | pmid = 20723248 | pmc = 2942809 | doi = 10.1186/1742-4682-7-34 | doi-access = free }}</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>

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="pharmk2">{{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>

DMT is primarily metabolized by [[monoamine oxidase A]] (MAO-A) into [[indole-3-acetic acid]] and to a much lesser extent in the liver by [[CYP2D6]] and [[CYP2C19]].<ref name="pharmk2"/><ref name="CYOP">{{cite journal | vauthors = Eckernäs E, Macan-Schönleben A, Andresen-Bergström M, Birgersson S, Hoffmann KJ, Ashton M | title = <i>N, N</i>-dimethyltryptamine forms oxygenated metabolites via CYP2D6 - an <i>in vitro</i> 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 orally it is metabolized by MAO-A in the liver and gut, and is thus not orally bioavailable unless a monoamine oxidase inhibitor is taken (as is naturally found in the ayahuasca brew).<ref name="McKennaTowers1984"/> When taken intravenously, DMT is primarily metabolized MAO-A in the circulatory system and brain.<ref name="pharmk" /> 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> 

Detailed pharmacokinetic analyses for inhaling or vaporizing DMT appear to be lacking.{{Citation needed|date=April 2025}}