Editing Dimethyltryptamine (section)

===Evidence in mammals===
Published in ''[[Science (journal)|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 chemistry|analytical studies]] looking for endogenously produced DMT in body fluids and tissues.<ref name="pmid779022" />

In 2013, researchers reported DMT in the [[pineal gland]] [[microdialysis|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&nbsp;mg/kg. However, this claim by Strassman has been criticized by David Nichols who notes that DMT does not appear to be produced in any meaningful amount by the pineal gland. Removal or calcification of the pineal gland does not induce any of the symptoms caused by removal of DMT. The symptoms presented are consistent solely with reduction in melatonin, which is the pineal gland's known function. Nichols instead suggests that [[dynorphin]] and other [[endorphins]] are responsible for the reported euphoria experienced by patients during a [[near-death experience]].<ref name= "pmid29095071">{{cite journal | vauthors = Nichols, DE | title = ''N'',''N''-Dimethyltryptamine and the pineal gland: Separating fact from myth | journal = Journal of Psychopharmacology | volume = 32 | issue = 1 | pages = 30–36 | date = Nov 2017 |pmid =29095071 |doi = 10.1177/0269881117736919 | doi-access = free }}</ref>

In 2014, researchers demonstrated the [[Immunomodulation|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 | pages = 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>{{cite journal | vauthors = Dean JG, Liu T, Huff S, Sheler B, Barker SA, Strassman RJ, Wang MM, Borjigin J | title = Biosynthesis and Extracellular Concentrations of ''N'',''N''-dimethyltryptamine (DMT) in Mammalian Brain | journal = Scientific Reports | volume = 9 | issue = 1 | page = 9333 | date = June 2019 | pmid = 31249368 | pmc = 6597727 | doi = 10.1038/s41598-019-45812-w | bibcode = 2019NatSR...9.9333D }}</ref>

The first claimed detection of [[Endogeny (biology)|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&nbsp;±&nbsp;8.6&nbsp;μg of dimethyltryptamine/24&nbsp;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> [[High-performance liquid chromatography|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<sup>−9</sup> 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="background:azure; vertical-align:middle; text-align:center; width:30px;" | Species
! style="background:azure; vertical-align:middle; text-align:center; width:60px;" | Sample
! style="background:azure; vertical-align:middle; text-align:center; width:400px;" | Results
|-
! rowspan="8" style="background:oldLace; vertical-align:top; text-align:center; width:30px;" | Human
| style="vertical-align:middle; background:oldLace; width:60px;" | [[Blood serum]]
| style="vertical-align:middle; background:oldLace; width:400px;" | < LOD (''n'' = 66)<ref name="pmid16095048" />
|-
| style="vertical-align:middle; background:oldLace; width:60px;" | [[Blood plasma]]
| style="vertical-align:middle; background:oldLace; width:400px;" | < LOD (''n'' = 71)<ref name="pmid16095048" /> &nbsp;♦&nbsp; < LOD (''n'' = 38); 1,000 & 10,600&nbsp;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; background:oldLace; width:60px;" | Whole blood
| style="vertical-align:middle; background:oldLace; width:400px;" | < LOD (''n'' = 20); 50–790&nbsp;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; background:oldLace; width:60px;" | Urine
| style="vertical-align:middle; background:oldLace; width:400px;" | < 100&nbsp;ng/L (''n'' = 9)<ref name="pmid16095048" /> &nbsp;♦&nbsp; < LOD (''n'' = 60); 160–540&nbsp;ng/L (''n'' = 5)<ref name="pmid11763413" /> &nbsp;♦&nbsp; 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; background:oldLace;"
| style="width:60px;" | Feces
| style="width:400px;" | < 50&nbsp;ng/kg (n&nbsp;= 12); 130&nbsp;ng/kg (''n'' = 1)<ref name="pmid16095048" />
|- style="vertical-align:middle; background:oldLace;"
| style="width:60px;" | Kidney
| style="width:400px;" | 15&nbsp;ng/kg (''n'' = 1)<ref name="pmid16095048" />
|- style="vertical-align:middle; background:oldLace;"
| style="width:60px;" | Lung
| style="width:400px;" | 14&nbsp;ng/kg (''n'' = 1)<ref name="pmid16095048" />
|-
| style="vertical-align:middle; background:oldLace; width:60px;" | [[Lumbar puncture|Lumbar]] CSF
| style="vertical-align:middle; background:oldLace; width:400px;" | 100,370&nbsp;ng/L (''n'' = 1); 2,330–7,210&nbsp;ng/L (''n'' = 3); 350 & 850&nbsp;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="background:#dcdcdc; vertical-align:top; text-align:center; width:30px;" | Rat
| style="vertical-align:middle; background:#dcdcdc; width:60px;" | Kidney
| style="vertical-align:middle; background:#dcdcdc; width:400px;" | 12 &amp; 16&nbsp;ng/kg (''n'' = 2)<ref name="pmid16095048" />
|- style="vertical-align:middle; background:#dcdcdc;"
| style="width:60px;" | Lung
| style="width:400px;" | 22 & 12&nbsp;ng/kg (''n'' = 2)<ref name="pmid16095048" />
|- style="vertical-align:middle; background:#dcdcdc;"
| style="width:60px;" | Liver
| style="width:400px;" | 6 & 10&nbsp;ng/kg (''n'' = 2)<ref name="pmid16095048" />
|-
| style="vertical-align:middle; background:#dcdcdc; width:60px;" | Brain
| style="vertical-align:middle; background:#dcdcdc; width:400px;" | 10 &amp; 15&nbsp;ng/kg (''n'' = 2)<ref name="pmid16095048" /> &nbsp;♦ &nbsp;Measured in [[Synaptic vesicle|synaptic vesicular]] [[Fractionation|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; background:honeyDew; width:30px;" | Rabbit
| style="vertical-align:middle; background:honeyDew; width:60px;" | Liver
| style="vertical-align:middle; background:honeyDew; width:400px;" | < 10&nbsp;ng/kg (''n'' = 1)<ref name="pmid16095048" />
|}

A 2013 study found DMT in [[Microdialysis|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 [[5-MeO-DMT|''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>