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Is DMT produced in the human brain?
Q: I read that DMT is produced in the brain, but then I heard that was just a rumor. I also read somewhere that eating a candy bar, tryptophan vitamin supplements, and an MAOI will cause your brain to produce its own DMT.

A: As of January 2013, this question of whether DMT is produced in the brain does not have a simple yes or no answer. It has not yet been conclusively demonstrated that DMT is produced in the living human brain, but there are strong reasons to believe that it might be, as well as technical issues that make the theory difficult to verify.

The presence of DMT in human blood and urine has been conclusively reported in a number of papers (Riceberg and van Vunakis, 1978). For many years, its presence in urine was tied to people with schizophrenia and psychosis (Jacobs and Presti, 2005). There is no question that DMT is naturally produced in the human body.

The enzymes necessary to produce DMT from tryptamine and serotonin--N-methyltransferase (NMT) and indolethylamine N-methyltransferase (INMT)--as well as the mRNA necessary to produce the enzymes have been shown to exist in human tissues outside the brain. While found in the spinal cord, these were not identified in the brain itself (Thompson et al., 1999). However, it remains quite possible that they are present in areas of the brain other than those studied by Thompson et al., or that they are present in amounts too small to have been detected, or that the necessary genes are only expressed (and the mRNA produced) under certain conditions.

In one key study looking at this issue from 1971, Mandell and Morgan flooded extracted brain tissue with tryptamine in vitro (in petri dishes) and measured the DMT that was produced. However, they did not show that this actually happens in living tissue with normal amounts of tryptophan.

DMT is so readily broken down by the MAO enzyme that one researcher, Nicholas Cozzi, co-author of a 2009 paper on the topic published in Science, speculates that the problem might simply be one of detection: "DMT itself is so fleeting, that it seems one might have to take 'heroic' measures such as obtaining fresh brain tissue from a patient on MAO inhibitors or freezing brain tissue immediately upon collection to prevent the disappearance of any DMT. We know that DMT can be detected in rat brain tissue from animals pretreated with an MAO inhibitor (this was elegantly demonstrated in the Saavedra/Axelrod work), but as far as I know, this hasn't been done with human tissue." (Cozzi, personal communication, 2010)

Cozzi et al. published a poster in 2011 demonstrating that small primate (Rhesus macaque) brain tissue (including pineal gland) has the correct enzymes to create DMT but did not directly measure DMT in those tissues.

While it has been established that DMT is produced in the human body, it is not yet possible to say definitively that it is produced in the human brain. With some conflicting evidence, signs point to DMT being produced in the brain in small quantities at a limited number of (as yet unidentified) sites.

To answer the second part of your question, taking an MAOI and eating a candy bar will not have effects similar to smoking DMT or taking ayahuasca. Many people have been prescribed long-acting, very powerful MAOIs and have not reported that kind of effect.

- earth

For a discussion of whether DMT is specifically formed in the human pineal gland, see DMT and the Pineal: Fact or Fiction? (Hanna, 2010).

Selected quotes from related papers:

"DMT can be produced by enzymes in mammalian lung (11) and in rodent brain (12). DMT has been found in human urine, blood, and cerebrospinal fluid (9, 13). Although there are no conclusive quantitative studies measuring the abundance of endogenous DMT because of its rapid metabolism (14), DMT concentrations can be localized and elevated in certain instances. Evidence suggests that DMT can be locally sequestered into brain neurotransmitter storage vesicles and that DMT production increases in rodent brain under environmental stress (8)." (Fontanilla et al., 2009)

In a review article that summarizes the results of previous research evidence for endogenous production of DMT (and other hallucinogens) in humans, Rosengarten and Friedhoff report that enzymes necessary to produce DMT have clearly been shown to be present in living tissue, "Tryptamine, or NMT, can be enzymatically converted to DMT by a SAM-dependent enzyme or enzymes shown to be highly active in lung or adrenal, particularly of the rabbit. This enzyme system can be demonstrated in brain, but its activity is very low. Similar findings have been made with regard to the formation of bufotenine from serotonin." (Rosengarten and Friedhoff, 1976)

"We have recently demonstrated the presence of this enzyme in the brain of rat, with the highest specific activity in the brain stem and the lowest in cortical areas. In addition, we have evidence of the presence of this enzyme in infant parietal and adult frontal cortical tissue taken incidentally from man during neurosurgical procedures." (Morgan and Mandell, 1969)

"More controversial is the presence of DMT in brain. Some researchers posit that the synthesis of DMT in brain is not physiologically significant (Thompson et al., 1999; however, consider the arguments of Jones, 1983; Reader et al., 1988). Other researchers propose that DMT levels increase in the mammalian brain during stress, whereupon DMT may act as an endogenous anxiolytic (for discussion, see Jacob and Presti, 2005)." (Burchett, 2006)

"The potent hallucinogenic effects of pure DMT in humans were first reported by Szara [7] in 1956. Then, in 1965, DMT, tryptamine and 5-hydroxy-N,N-dimethyltryptamine (bufotenine) were reported as normal constituents of human urine and blood [8] [...] We have reviewed the current research on INMT and AADC activity, illustrating that their participation in DMT biosynthesis is biochemically very reasonable. We have also proposed a major role for DMT in the trace amine system. This proposal offers a neurochemical explanation for heretofore ill-understood aspects of DMT pharmacology, especially at low doses. Our proposed scenario also includes the hypothesis that increased DMT or tryptamine production could suppress psychotic activity, rather than aggravate it." (Jacob and Presti, 2005)

References #
  1. Burchett SA, Hicks TP. "The mysterious trace amines: protean neuromodulators of synaptic transmission in mammalian brain." Prog Neurobiol. Aug 29, 2006;79(5-6):223-46. [Abstract]
  2. Cozzi N. Personal communication. August 2010.
  3. Fontanilla D, Johannessen M, Hajipour AR, Cozzi NV, et al. "The Hallucinogen N,N-Dimethyltryptamine (DMT) Is an Endogenous Sigma-1 Receptor Regulator." Science. Feb 2009;323(5916):934-7. [Abstract]
  4. Jacob MS, Presti DE. "Endogenous psychoactive tryptamines reconsidered: an anxiolytic role for dimethyltryptamine." Med Hypotheses. 2005;64(5):930-7. [Abstract]
  5. Mandell AJ, Morgan M. "Indoleethylamine N-methyltransferase in human brain." Nat New Biol. Mar 4, 1971;230(11):85-7. [Abstract]
  6. Morgan M, Mandell AJ. "Indole(ethyl)amine N-methyltransferase in the brain." Science. Aug 1, 1969;165(892):492-3. [Abstract]
  7. Riceberg LJ, Vunakis HV. "Determination of N,N-dimethylindolealkylamines in plasma, blood and urine extracts by radioimmunoassay and high pressure liquid chromatography." J Pharmacol Exp Ther. Jul 1, 1978;206(1):158-66. [Abstract]
  8. Rosengarten H, Friedhoff AJ. "A review of recent studies of the biosynthesis and excretion of hallucinogens formed by methylation of neurotransmitters or related substances." Schizophr Bull. 1976;2(1):90-105. [Abstract]
  9. Saavedra JM, Axelrod J. "Psychotomimetic N-methylated tryptamines: formation in brain in vivo and in vitro." Science. Mar 24, 1972;175(28):1365-6. [Abstract]
  10. Thompson MA, Moon E, Kim UJ, Xu J, et al. "Human indolethylamine N-methyltransferase: cDNA cloning and expression, gene cloning, and chromosomal localization." Genomics. Nov 14, 1999;61(3):285-97. [Abstract]
  11. Cozzi NV, Mavlyutov TA, Thompson MA, Ruoho AE. "Indolethylamine N-methyltransferase expression in primate nervous tissue" Soc. Neurosci.. 2011;37:840.19.

Asked By : aaron
Answered By : earth
Edited By : fire, spoon
Published Date : 9 / 2 / 2010
Last Edited Date : 2 / 20 / 2015
Question ID : 3146

Categories: [ Pharmacology ] [ DMT ] [ Chemicals ]

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