Talk:N,N-Dimethyltryptamine

Legal Status

This section currently claims that DMT is not dangerous, non-toxic, and non-addictive, but doesn't include a cite for any of these. Including this without a citation is at best NPOV and at worst dangerously misleading. It seems to me that this whole paragraph should be removed or backed up with some legitimate scientific studies.96.240.1.196 (talk) 07:57, 1 December 2008 (UTC)

OK, if you can find some reference(s) to its putative toxicity and addiction potential, please post it in the article. Otherwise, it would be NPOV to paint devils on the wall. It is, however, probably a bit reckless to claim that a powerful psychoactive agent like DMT is not dangerous, yet despite a considerable amount of medical and pharmacological research, DMT is surprisingly lacking in toxicity and addiction potential.Jace1 (talk) 09:52, 13 April 2009 (UTC)

I don't have access to it right now, but the Wallach article cited elsewhere, as well as a couple Halpern articles make it clear that there is little or no known toxicity to DMT. Nathan McKnight -- Aelffin (talk) 11:57, 23 May 2010 (UTC) Nobody is trying to write devils on the wall but if no legitimate sources are available maybe it should just be noted that it hasn't been proven one way or the other. —Preceding unsigned comment added by 209.40.209.76 (talk) 00:19, 27 August 2010 (UTC)

It also wasn't proven one way or another whether Strawberry is toxic. You can't assume any substance is toxic "by default" - if a substance was tested and wasn't found to be toxic than it can be considered safe to assume it isn't. 89.138.215.52 (talk) —Preceding undated comment added 04:08, 15 May 2011 (UTC).

Non-notable hypothesis

The Wallach reference (Wallach J (2008). "Endogenous hallucinogens as ligands of the trace amine receptors: A possible role in sensory perception". Med Hypotheses. in print (in print): in print. doi:10.1016/j.mehy.2008.07.052. PMID 18805646.) has been repeatedly reinserted. This is not a non-notable hypothesis by a non-notable author in a scientifically non-reliable source (in addition of being cutter nonsense - but that is not the point here), please see Wikipedia:Notability. Wikipedia is not a forum to make non-notable theories notable (see Wikipedia:What Wikipedia is not. I kindly ask you not to reinsert that section. Thanks, Cacycle (talk) 05:49, 6 December 2008 (UTC)

What precisely is non-notable about it? For that matter, what makes the source non-reliable? It's just as valid as any other information in the article, if not more (I mean, it's better than erowid, from which half of the information in the article seems to be taken). I'm not the author of this section, but I think it's definitely worth keeping. A dullard (talk) 18:22, 11 December 2008 (UTC)

Please could you explain why you think this is a notable hypothesis by Wikipedia standards? The journal Medical Hypotheses lets anybody publish original ideas without any professional oversight, making it a scientifically non-reliable source. The ideas presented in that article are at least as whacko as the rest of the section - the difference is that the other ideas are well known and widely circulated and/or have some historical relevance. Cacycle (talk) 02:33, 12 December 2008 (UTC)

Truthfully, I didn't know that the journal (or any journal, for that matter) was so lax; I apologize for what might have been considered a curt comment. In that case, feel free to remove it, but also realize that the reference immediately before it is also from Medical Hypotheses (although I think it might be more notable without necessarily being more reliable). I should have known that something written so plainly couldn't be true-- compare, for example, with this: http://www.ncbi.nlm.nih.gov/pubmed/9768567?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_Discovery_RA&linkpos=3&log$=relatedarticles&logdbfrom=pubmed. Apologies. A dullard (talk) 06:24, 12 December 2008 (UTC)

The reference by Wallach may or may not be a "non-notable hypothesis", and the author may be non-notable. However, to characterize Medical Hypotheses as a scientifically non-reliable source of information is just an opinion, and not fact. But, perhaps someone could take the time to compile a list of the journals they think we should consider as medically valid, and those that are not (?). I just checked, and Medical Hypotheses is (still) abstracted in PubMed, and is (still) peer reviewed. I personally think it would be a pity for us to discard any potentially useful information on this interesting topic. However, the citation of the article by Wallach currently appears twice in the reference section, while once should suffice.Jace1 (talk) 14:47, 11 April 2009 (UTC)

First, WP:NOTE is only applicable to the article as a whole. To quote: "...notability guidelines only outline how suitable a topic is for its own article. They do not directly limit the content of articles." (emphasis my own) Second, Medical Hypotheses is a peer-reviewed scientific publication, which is by definition WP:Reliable. Finally, on a different note, what do we think about creating a separate heading under which to group scientific hypotheses like those of Wallach to distinguish them from the pure speculation of folks like McKenna (and I mean Terence no disrespect, but there is a difference). Nathan McKnight -- Aelffin (talk) 16:31, 21 May 2010 (UTC)

I'm sorry but unless I'm utterly mistaken, Medical Hypotheses is in fact not a peer-reviewed journal, or at least has not been until very recently. This has been the subject of considerable controversy lately, as the journal has been put under pressure by the publisher to adopt peer review. The chief editor and several members of the editorial staff have resisted this greatly and, according to news stories, resigned in response. I'm not sure what the situation is right now, but I'm quite certain that a paper from 2008 would not have been peer reviewed.Avaricius (talk) 19:55, 28 May 2010 (UTC)

Hmmm...you're right about Medical Hypotheses not being peer reviewed. My mistake. Still, it is a scientific journal and if I'm not mistaken Wallach is a respected researcher, so I think we should consider his hypotheses valuable--and of course the factual accuracy of his information apart from the speculative hypotheses I think is still quite valid. What I'm staying is that I think publication in Medical Hypotheses may warrant caution when considering inclusion of the hypotheses themselves, but any background information and factual claims in the articles should be treated as any other scientific publication...which is to say, Medical Hypotheses may be speculative, but not nearly so speculative as, say McKenna's publications. Nathan McKnight -- Aelffin (talk) 13:48, 13 June 2010 (UTC)

Kundalini

I think its worth mentioning the role DMT may play in kundalini energy phenomenon, as described in the works of Ganapathy and Dixon. Kundalini energy phenomenon are recognized by psychoanalysts, tranpersonal psychologists, and are mentioned in the DSM - so this is a legitimate subject and a legitimate hypothesis regarding this DMT-Kundalini connection. —Preceding unsigned comment added by Zergshaman (talk • contribs) 21:53, 27 January 2009 (UTC)

Still seems pretty fringe-like to me. Also it's still only a hypothesis. Has this research been published in peer reviewed journals? Is this something more than just a hypothesis? I'm beginning to think that the whole speculations section needs rewriting as a lot of it seems to be speculation and fringe.TheRingess (talk) 21:56, 27 January 2009 (UTC)

Yes, seems fringe-ish. I just tried to search for connections between Ganapathy, Dixon and Kundalini, and came up with nothing. If DMT is involved in Kundalini, then I suspect many other neurotransmitters are as well. Speculations on the putative endogenous function(s) of DMT should be primarily limited to those that are visual and psychedelic, like dreams and some forms of visual hallucinatory psychosis.Jace1 (talk) 10:03, 13 April 2009 (UTC)

If it's by psychologists in the DSM-IV-TR: Diagnostical Statistical Manual of Mental Disorders (the bible of therapists and psychiatrists alike) it is not on the fringe. The book is not written by one person, it's written by the heavy hitters in areas of expertise and usually people with at least one Ph.D. from a Top 30 University. Very very smart people combing over very dense statistics, maybe you guys didn't know what the DSM was or didn't read the introduction about what separated the DSM-IV from the DSM-IV-TR, I would recommend you do if you are questioning the fringe status of the DSM. —Preceding unsigned comment added by 76.89.223.250 (talk) 07:49, 11 June 2009 (UTC)

It is not the DSM-IV, the DSM-IV-TR, or even Kundalini that I would consider to be peripheral to this article, but the putative DMT-Kundalini connection. However, if you think it is important, please do start a new article on that and add a link to this one. Otherwise, there does not seem to be any evidence or even an existing hypothesis to support this speculation.Jace1 (talk) 14:19, 9 July 2009 (UTC)

The DSM does not recognise "kundalini energy", nor could it. It would be akin to the DSM recognising the holy spirit. Ninahexan (talk) 08:36, 29 April 2010 (UTC)

See also

Some of the links in the "See also" section seem irrelevant. For example, Joe Rogan's article talks about DMT briefly, but I don't think he's all that vital to DMT itself. Graham Hancock's article doesn't even mention DMT. Is there any reason not to remove those? A dullard (talk) 05:21, 23 May 2010 (UTC)

Requested indefinite semi-protection

Since this article is about a recreational drug,

- and has been seeing constant minor vandalism,
- from a wide range of IP addresses,
- few or none of which are contributing,
- while valid editing is in progress,
- and this article is a popular b-class article,
- of a type for which Wikipedia is reputable,

I have requested indefinite semi-protection.

It is most likely that administrators will immediately grant a limited period (hopefully a long one), but this is precisely the sort of article that will attract random vandals forever, so if the protection granted is temporary and random vandals start up again afterwards please request indefinite semi-protection again. Aaron Walkhouse (talk) 02:50, 20 June 2010 (UTC)

Harshness of Inhaled DMT Smoke

I added a snippet about eliminating the 'razor-blade' sensation commonly experienced with inhaled DMT. This sensation is caused by contaminating hydroxyl ions left over from common acid-base extraction techniques and can be neutralised by a splash of a weak acid (e.g. lemon juice) into the bong chamber and mouthpiece. Other methods, such as adding a sodium carbonate wash have been discussed on forum sites. My contribution was reversed as it was unsourced, however it is already known that hydroxyl ions will contaminate any preparation made from an acid-base extraction; it is also obvious that breathing in (effectively concentrated) hydroxide will burn the upper respiratory tract. The facts I have stated are verifiable and within the remit of A-level/high school chemistry knowledge, although they are arguably from too many sources to support a single snippet. I think it's important to accurately and unbiasedly document how irritating DMT is to the respiratory tract - it is possible to (wrongly) infer that it is quite harsh indeed with the currently included and *unsourced* subjective reports of DMT inhalation. MaxwellEdisonPhD (talk) 17:36, 02 August 2010 (UTC)

Besides the fact that you still have not provided a verifiable source for this uncommon knowledge, there is also the fact that Wikipedia is not a manual or a how-to guide. See WP:NOTAMANUAL. Doctorx0079 (talk) 22:23, 2 August 2010 (UTC)

Dangers

WHY HAVE THIS SECTION BEEN DELETED?!! DMT IS DANGEROUS AND PEOPLE SHOULD BE AWARE OF THE DANGERS!

DMT bears the full range of dangers known from LSD. A person may not come back from the trip which externalizes itself in drug psychosis, flashbacks and Hallucinogen Persisting Perception Disorder (HPPD). These dangers are often underestimated, since the duration of DMT effects last for minutes, in contrast to LSD effects which last for many hours. There is a lethal dose of DMT. However, it is hard to reach lethal dose by inhaling DMT because the person loses control of the body. In the majority of cases a person may die not directly of DMT but on the after effects DMT may cause in the psyche of the person. In the community of LSD consumers there is a popular example that a person believes he could fly and jump out of the window. DMT, just like LSD, may activate dangerous beliefs causing a person to do dangerous things. In the movie Inception it is well demonstrated how psychosis may externalize itself: the woman believes her life is a dream and she can awake from that dream by committing a suicide. On DMT, people report that their consciousness transferred to another dimension. Some start to believe that their whole body has moved to another parallel reality and they can come back by committing a suicide, which is very close to the plot of the named film! Just recently (July 2010), a seventeen year old Danielle Jacobsen drowned after having consumed DMT. —Preceding unsigned comment added by 85.176.32.88 (talk) 07:49, 4 August 2010 (UTC)

If you click the "Article" tab and then click "View History" you can see why the section was deleted. Hopefully you can understand those directions even if English is not your first language. Doctorx0079 (talk) 20:59, 4 August 2010 (UTC)

That would be like removing an article about water because water can be fatal if you drink too much. Your describing tired cliches, no offense but those have no place here unless you have actual proof and if you do they should be in the article but saying the article needs to be removed is just silly. I feel the need to point out, how do you know these beliefs are crazy? How do you know your consciousness doesn't go to another reality when you die? These are not beliefs caused by acid and DMT, they are beliefs that many people have and some people (without the use of drugs) act on. Please stop with the "sky is falling" speech until you educate yourself on a few subjects. 209.40.209.76 (talk) 00:28, 27 August 2010 (UTC)

@209.40.209.76 Agreed.--206.28.43.119 (talk) 17:58, 12 September 2010 (UTC)

Added revised “Dangers” section from existing references based on feedback from Doctorcito and Pontificalibus. Content is based on references, other Wikipedia articles, mathematical logic (e.g. If a=b and b=c, then a=c) and common sense. Please let me know where you need reference help or have confusion. Please try to be specific. ----Raypurdy (talk) 10:35, 31 November 2010 (UTC)

Your conjecture that DMT in gum arabic causes serotonin syndrome and cancer amounts to original research and is not suitable for inclusion. Where are your references that discuss this theory in reliable sources? Wikipedia is not a place for publishing your own ideas or original thought.--Pontificalibus (talk) 15:43, 30 November 2010 (UTC)

Questionable title: Raypurdy created twice a section entitled "Dangers". There is no need nor relevance to create a section with such a title, that departs from NPOV and Project Pharmacology Guideline: all can be said either under "Side effects", an enlarged "Side effects and complications" section or a separate "Complications" section.

Questionable content: Much of the content brought by Raypurdy is speculation about Gum Arabic, and unrelated to the subject of the article which is DMT, not Gum Arabic. No reliable source reporting presence of DMT in Gum Arabic has been provided. For mention of Gum Arabic to have any meaningfulness in the article, it is necessary to provide credible citations reporting:

1. that DMT is present at biologically significant levels in samples of commercially available Gum Arabic;
2. that biologically significant levels of DMT have been detected in plasma of humans or test animals after oral administration of Gum Arabic.

Meanwhile, all content about Gum Arabic will be edited. --Doctorcito (talk) 16:22, 30 November 2010 (UTC)

Wrong, first comes qualitative analysis followed be quantitative analysis. Qualitatively, I need to show:

1. That DMT is in Gum Arabic. DMT is found in Acacia Senegal gum. Another name for Acacia Senegal gum is Gum Arabic. Done
2. Identify groups that consume Gum Arabic (e.g. children, beer and spirit drinkers)
3. Look for symptoms of DMT exposure as a result of receptor stimulation from these groups.

The “Dangers” section, http://en.wikipedia.org/w/index.php?title=Dimethyltryptamine&oldid=399734510 that has been deleted, identifies this qualitative information that represents a “Danger”. Now, if you want to explain to parents, beer and spirit drinkers why they shouldn’t worry about consumption quantity of an illegal psychedelic drug, more powerful than LSD, then keep me out of it. It’s against the law to distribute and consume DMT. -- Raypurdy (talk) 11:45, 06 December 2010 (UTC)

You are right that in the industry Gum arabic is derived only from Acacia senegal material. Now let's examine your citations:

Link of your citation #1: "Species not found in database". A query about Acacia senegal on Duke's database returns "DIMETHYLTRYPTAMINE Plant: DUKE1992A", with Duke's Handbook (1992) as sole reference (which is a secondary source. So the webpage is a tertiary source, with no mention of a primary one. In addition, Duke's database and Handbook are not particularly reliable when it comes about psychoactive plants. Ott is a much more reliable source).

Link of your citation #2: Webpage in Polish without any reference, mentioning Acacia senegal and DMT in the same line.

Link of your citation #3: Webpage of a vendor indicating "DMT in leaf" (italics added) of Acacia senegal and referring without precision to Shulgin's PIHKAL.

Link of your citation #4: A Wikipedia article with "multiple issues" and no citations.

Link of your citation #5: A paper by Indian researchers mentioning that "The alkaloids found in Acacia senegal include less than .1% DMT and NMT in leaf" (italics added). Two secondary sources included (so its a tertiary one), from 1980 and 1981.

Link of your citation #6: Page of a webforum citing Ott's Ayahuasca Analogues (1994) as reporting "trace amount" of DMT in Acacia senegal "leaves" (italics added).

Link of your citation #7: Another page from a webforum mentioning, without reference, "DMT, in the leaf" (italics added) for Acacia senegal.

Link of your citation #8: Webpage in Italian where "DMT" is put besides Acacia senegal. No reference.

Link of your citation #9: Webpage reproducing without permission a table from Ott's Ayahuasca Analogues, listing Acacia senegal with DMT in leaves (the reference given by Ott is omitted, though).

Link of your citation #10: Webpage mirroring the Wikipedia article on Acacia. States this: "Less than 0.1% DMT in leaf, NMT, other tryptamines. DMT in plant, DMT in bark". Citations are your citations #1, #2 and #3. Circularity, someone?

Link of your citation #11: Another webpage mentioning DMT "in the leaf" (italics added) for Acacia senegal, without reference.

Results: Hint that low concentrations of DMT may have been detected in leaves of Acacia senegal. Not a single primary source cited in all these documents. So I checked Jonathan Ott's Ayahuasca Analogues (1994). There is in fact one paper that reported detection of DMT in Acacia senegal. In the leaves. And you know what? Gum arabic is not made with leaves: it is "is a natural gum made of hardened sap" (Gum arabic) "obtained from the stems and branches" (FAO). There is thus NO known direct or indirect evidence of DMT presence in industrial Gum arabic. Case closed. Please stop now posting your sourceless speculations. --Doctorcito (talk) 04:53, 7 December 2010 (UTC)

The reference Dr. James A. Duke's, CRC Press, “Handbook of phytochemical constituents of GRAS herbs and other economic plant” (1992) is excellent reference. Other Wikipedia articles have used this reference. CRC Press publishes reference standards for mathematics and science professionals. The Phytochemical and Ethnobotanical Databases were commissioned by the USDA. Dr. Duke has a PHD in botany and has authored many books.----Raypurdy (talk) 11:00, 20 December 2010 (UTC)

Please quote here (with page number) Jim Duke's Handbook passage where he mentions DMT being present in A. senegal gum, and the reference to at least one primary source/s he provided to support this claim. Unlike you, I have provided the existing primary reference on DMT finding in A. senegal (heck, I even made your homework), which was in leaves. As it is the sole existing, it is the only one cited by all authors who compiled the literature. Good luck with Jim Duke's Handbook to find another. Meanwhile your edit is suspended-reverted. --Doctorcito (talk) 18:42, 20 December 2010 (UTC)

Questionable content II: That DMT can cause alone noticeable serotonin toxicity (aka serotonin syndrome) at average psychedelic doses is at best a hypothesis in need of empirical support. Neither Sternbach's criteria for serotonin syndrome, nor Hunter serotonin toxicity criteria are satisfied in the clinical observations and data collected in the thorough study of Rick Strassman, even with the highest dose, judged "overwhelming" by most test persons. In particular, none of the neuromuscular signs that are the hallmark of serotonin toxicity were noted. Serious empirical, clinical data is thus required to allow to speak of serotonin toxicity in direct relation to DMT alone. Without one or more citation/s bringing such hard evidence, it is mere speculation. That will be edited. --Doctorcito (talk) 00:50, 3 December 2010 (UTC)

Rectal Administration

I think that this should be removed. It's not using a reliable source. Also, it doesn't even say the same thing as the source says as far as duration. I'm going to remove it. If anyone wants this to remain, please explain how an individual report is considered a reliable source. There should be something talking about rectal administration, but it should be accurate and using a reliable source of information. Five- (talk) —Preceding undated comment added 15:15, 24 August 2010 (UTC).

I agree, but for future reference, please leave an edit summary. For instance, here I would leave "Removed unreliable information. See talk page for details." I almost undid your change because I thought it was vandalism. Thank you. Mutinus (talk) 15:50, 24 August 2010 (UTC)

Endogenous DMT sources

In case anybody needs more citations for the presence of DMT in the body, here are a few...

Quote: “Dimethyltryptamine (DMT) is an endogenous hallucinogen with traditional use as a sacrament in the orally active preparation of ayahuasca.” 2010. V. Cakic et al. Dimethyltryptamine (DMT): Subjective effects and patterns of use among Australian recreational users. In: Drug and Alcohol Dependence 111 (2010) 30–37

Quote: “Identification of N-alkylatedtryptamines, such as DMT,as endogenous agonists for the Sig-1R based on the loss of DMT-induced hypermobility responses in the Sig-1R homozygous null knockout (KO) mouse has additionally added to the knowledge of agonist pharmacology at the Sig- 1R.” 2010. T-P. Su et al. The sigma-1 receptor chaperone as an inter-organelle signaling modulator. In: Trends in Pharmacological Sciences xx (2010) 1-10.

2010. J.A. Fishback et al. Sigma receptors: Potential targets for a new class of antidepressant drug. Pharmacology & Therapeutics 127 (2010) 271–282 Quote: “The endogenous ligand(s) for sigma receptors have yet to be conclusively identified. However, a number of candidates have been proposed including some neuroactive steroids, sphingolipids (Su et al., 1988; Ramachandran et al., 2009), and most recently N,Ndimethyltryptamine (DMT) (Fontanilla et al., 2009).”

Quote: “Endogenous hallucinogenic neurochemicals, in particular N,Ndimethyltryptamine (DMT), have recently been shown to activate a small subgroup of receptor sites called the trace amine associated receptors (Wallach, 2009).” 2010. B.A. Killinger et al. Salvinorin A fails to substitute for the discriminative stimulus effects of LSD or ketamine in Sprague–Dawley rats. In: Pharmacology, Biochemistry and Behavior 96 (2010) 260–265.

Quote: “There are two main pathways for the metabolism of the amino acid, tryptophan: the serotonin (5-HT) and kynurenine pathways. Of these, the 5-HT pathway has received the most attention in studying the pathophysiology of schizophrenia (SCH), initially, by formation of an endogenous hallucinogen, e.g. N,N-dimethyltryptamine, a 5-HT2A receptor agonist (Strassman et al., 1994)” 2010. M. Lee et al. Decreased plasma tryptophan and tryptophan/large neutral amino acid ratio in patients with neuroleptic-resistant schizophrenia: Relationship to plasma cortisol concentration. Psychiatry Research xxx (2010) xxx–xxx. --User:Aelffin 18:15, 1 November 2010 (UTC)

Thank you for the legwork: You've provided an interesting list of papers that propagate sloppy information about endoDMT. But unfortunately the point isn't to find papers citing other papers about INMT (EC= 2.1.1.49; the enzyme catalyzing biotransformation of tryptamine into DMT) and/or DMT detection in human and non-human organisms. It is to find papers actually reporting and detailing such detection, i.e. reliable quantitative analytical studies. The most recent and reliable ones are the following:

- J. Kärkkäinen et al. (2005) "Potentially hallucinogenic 5-hydroxytryptamine receptor ligands bufotenine and dimethyltryptamine in blood and tissues". Scandinavian Journal of Clinical & Laboratory Investigation, 65/3: 189-199.

- T. Forsström, J. Tuominen & J. Kärkkäinen (2001) "Determination of potentially hallucinogenic N-dimethylated indoleamines in human urine by HPLC/ESI-MS-MS". Scandinavian Journal of Clinical & Laboratory Investigation, 61: 547-556.

- Michael A. Thompson et al. (1999) "Human indolethylamine N-methyltransferase: cDNA cloning and expression, gene cloning, and chromosomal localization". Genomics, 61: 285–297.

- Richard M. Weinshilboum & Michael A. Thompson (1998) "Rabbit lung indolethylamine N-methyltransferase. cDNA and gene cloning and characterization". Journal of Biological Chemistry, 273: 34502-34510.

While these papers do confirm presence of INMT and trace amounts of endoDMT in organs like lungs and kidneys of humans and rodents, their results about the brain do not support the assertion, as currently worded, in the article discussed here ("DMT is naturally produced in small amounts in the brain and other tissues of humans and other mammals"). If on the one hand DMT traces were found in rat brain by Kärkkäinen et al. (2005), confirming thus older studies, on the other hand INMT was found to be lacking in human brain (Thompson et al. 1999) and neurons (Kärkkäinen et al. 2005), results also confirming a couple of older studies.

To summarize: Currently available evidence a) does not support DMT production in human brain, and b) does support presence of DMT traces in rat brain (but biosynthesis in rat brain still remains hypothetical). --Doctorcito (talk) 14:12, 2 November 2010 (UTC)

Three points. First, I'm not posting these articles in order to endorse any particular wording found in the current article, merely to provide source material for others to use to determine the best wording. Second, you are correct that DMT has not been detected in the human brain, but it has been detected in other human (and mammalian) tissues, thus it is an endogenous compound, regardless of where in the body it is produced. Finally, you say that "...the point isn't to find papers citing other papers..." but according to Wikipedia policy, that is preciesely the point. The sources you supplied are primary sources, while the sources I supplied are secondary sources, and as I understand it, WP:Secondary indicates that these should be the main source of information for our articles. Nathan McKnight -- Aelffin (talk) 15:20, 9 November 2010 (UTC)

Manifestly we do agree about DMT being an endogenous substance in mammals, humans included, and that's certainly the most important. My point in fact is about authors who propagate in the peer-reviewed literature the mis-information that DMT has been evidenced or is produced in human brain.

About your last point, even if I may have sounded a bit harsh to your ears (sorry for that), you shouldn't invoke Wikipedia policy here: only two of the articles you cited would qualify as secondary sources ("Unlike in the humanities, scientific and medical peer reviewed sources are not generally considered secondary unless they are a review or a meta-analysis"), and none of those 2 is dedicated to the topic discussed here. In fact, since the famous review article "N,N-dimethyltryptamine: an endogenous hallucinogen", made by researchers from the Alabama group (Steven Barker, John Monti and Samuel Christian), which was published in 1981, there have been no peer-reviewed review article dedicated to endogenous DMT. And the proposition "survey of previous work in the field in a primary peer-reviewed source is secondary" wouldn't be of any real help either: The most relevant surveys of previous works on detection of endogenous DMT or on INMT assays precisely are to be found in the articles I cited (they obviously also do cite other papers). If you had to select accounts about results of studies on oranges, would you prefer narratives of people presently working on apples, or reports of people currently doing research on oranges? ----Doctorcito (talk) 23:09, 9 November 2010 (UTC)

In response to your last question...it depends upon what I'm trying to establish. If the simple fact that DMT is an endogenous substance is the point being made, then I agree the most relevant sources would be those for which eDMT/INMT is the focus. However, if the point being made is that eDMT/INMT is widely accepted in the pharmacological community, then a broad range of sources would be valuable. On the subject of secondary sources, we may have to agree to disagree since--if I recall correctly--at least some of the articles I quoted treat eDMT in their field survey sections, and since primary reliance on "the most relevant" sources would seem not to exclude auxilliary reliance upon less relevant sources. :) Nathan McKnight -- Aelffin (talk) 23:30, 10 November 2010 (UTC)

Also, I don't recall reading in those papers any propogation of the myth of eDMT in the brain. Although admittedly, I only skimmed them. Nathan McKnight -- Aelffin (talk) 23:33, 10 November 2010 (UTC)

Thank you for your constructive, well thought-out contribution to this discussion. I do agree with with the points you made.

In case you would wonder, I did train in neuroscience, with specialization in neuropharm research ;-) and do actively follow developments about endoDMT since more than two decades (I also made a survey of the topic in a peer-reviewed review article - alas not in English). This to indicate that I have a rather comprehensive knowledge of the topic, and explain why I sometimes seem to overreact :-)

In the expanded "Biosynthesis" section, which will include results of analytical studies, I think it is crucial to stick to relevancy and accuracy, as one of its functions will be to provide a reliable database of sort, useful both to readers and to contributors who deal with endoDMT in the rest of the article.

Your remarks make me think that it would possibly be interesting and useful to write an endnote, or a subsection, on the contrasted ways the endoDMT topic is treated in recent peer-reviewed literature, mostly in regard of the sources they cite (the "DMT-in-human-brain" myth is propagated by people who cite outdated sources - And you were apparently right that the articles you listed don't fall into this category). If you're interested... ----Doctorcito (talk) 12:23, 12 November 2010 (UTC)

Thanks. Good to have you here too. It's nice to see some neuroscientists keeping track of things here on Wikipedia. What language did you publish your survey in? Nathan McKnight -- Aelffin (talk) 16:26, 13 November 2010 (UTC)

In French, which is my first language. ----Doctorcito (talk) 18:55, 13 November 2010 (UTC)

Biosynthesis (and detection in mammals)

I've started to -hopefully- improve the "Biosynthesis" section. My proposal is to expand it: It is obviously the right place in the article to summarize the results in mammals of analytical studies that have evidenced DMT and the enzyme tryptamine-N-methyltransferase (well, at least since 1999 everybody in the primary literature call it "indolethylamine N-methyltransferase", a convenient move as it allows use of its acronym: INMT). To include there such a summary would provide a sound and relevant basis for subsequent mentions of or allusions to endogenous DMT production. ----Doctorcito (talk) 22:48, 7 November 2010 (UTC)

In order to further improve this section, I made a more detailed and accurate image of the biosynthetic pathway. It now includes all steps, with the relevant details (enzymes, cofactor, products), highlights changes (in red), and figures the methyl groups (more telling when about a transmethylation!) The size of this image was tailored to fit as a thumb without reduction (-> optimal resolution), and to visually interfere as little as possible with the global layout of the article. I will of course welcome suggestions to ameliorate this image (NB: size cannot be reduced without losing resolution).

The part of the section directly dealing with the image has been adapted accordingly. —Preceding unsigned comment added by Doctorcito (talk • contribs) 21:03, 8 November 2010 (UTC)

Rationale for expanding (a little) on technical history and details

In a couple of recent scientific papers, including Wallach's one (published in Medical Hypotheses) which is cited in the article and already discussed above in this page, one can find the referenced statements that DMT has been shown to "occur" or to be "produced" in human brain. It is thus fair to give here potential readers of these papers enough accurate and verified information to allow them to 1) appraise the relevancy of the references backing those statements, and 2) evaluate the overall credibility of the latter. ----Doctorcito (talk) 20:07, 13 November 2010 (UTC)

I've read the Wallach paper, but I don't have access to it right now. Does he cite any study backing this claim up? Since you seem to be familiar with this topic, where does this myth (if indeed it is a myth) originate? Nathan McKnight -- Aelffin (talk) 00:38, 14 November 2010 (UTC)

• About Wallach, here is the first phrase of his introduction:

"N,N-Dimethyltryptamine (DMT), 5-hydroxy N,N-dimethyltryptamine(bufotenine) and 5-methoxy N,N-dimethyltryptamine(5-MeO-DMT) have long been accepted as naturally occurring components of human blood, brain and cerebral spinal fluid." (italics added)

The 4 references he put to back this are the following:

• Axelrod T. Enzymatic formation of psychotomimetic metabolites from normally occurring compounds. Science 1961;134:343.
• Corbett L, Christian ST, Morin RD, Benington F, Symthies JR. Hallucinogenic Nmethylated indolealkylamines in the cerebrospinal fluid of psychiatric and control populations. Br J Psychiat 1978;132:139–44.
• Franzen Fr, Gross H. Tryptamine, N,N-dimethyltryptamine, N,N-dimethyl-5-hydroxytryptamine and 5-methoxy tryptamine in human blood and urine. Nature 1965;206:1052.
• Angrist BS, Gershon G, Sathananthan RW, et al. Dimethyltryptamine levels in blood of schizophrenic patients and control subjects. Psychopharmacology 1976;47:29–32.

None of these studies can back the statement that DMT has "long been accepted as a naturally occurring component of human brain".

• About the "myth".

I am glad you asked this question because it makes me realize that this also can be an interesting topic to cover in the article.

I do in fact currently distinguish two aspects in the phenomenon:

1. One is mere mis-information spread in the scientific literature by people who either 1) just don't properly do their homework (even with generalization of the Interwebs, a serious, in-depth survey of the literature still takes time), or 2) cherry-pick or misrepresent citations seemingly fitting their a priori convictions. Just common everyday bad science in both cases :-D
2. The second aspect is the myth proper, in an anthropological sense (I also did train in anthropology, at a postgraduate level ;-) ): Propagated in the popular literature (Strassman's DMT book comes to mind) and on the Interwebs, it is embodied (the mark of a true myth) by people who seclude themselves during days when not weeks in total darkness to live the myth of altered consciousness experiences triggered by 'enhanced DMT production and release by the pineal gland' (it is obvious and a well established fact that altered consciousness experiences do happen in such settings; and it is also obvious that there are no reliable scientific bases to 1) support the claim that DMT is produced in human brain (pineal gland included), and 2) to causally relate those experiences to endogenous DMT).

The myth feeds upon every bit of info that appears to give it credence in the scientific literature (i.e. on aspect #1). A reason why I think it is important for Wikipedia to be the repository of reliable, relevant and accurate information on this topic (hopefully, it will become the best in town) :-) ----Doctorcito (talk) 16:36, 14 November 2010 (UTC)

Maybe I'm splitting hairs here (after all, isn't that what sicence is about? :D)...but there is a difference between "occurring in the brain" and "produced by the brain". I'll agree that there isn't a shred of evidence for the latter statement (and while there are significant issues with Strassman's work, IIRC, he was careful to point out that pineal eDMT was speculation on his part). As for the former statement...if we are agreed that DMT is a naturally occuring component of blood and (presumably) we are agreed that blood is naturally occuring in the brain, then does it not follow that DMT occurs naturally in the brain, as Wallach states? Nathan McKnight -- Aelffin (talk) 19:47, 14 November 2010 (UTC)

At a quick glance, your biosynthesis draft looks pretty good. What seems to be the trouble with the table? Nathan McKnight -- Aelffin (talk) 20:45, 14 November 2010 (UTC)

Thanks for your positive appreciation. If the table looks centered, with a visible border of 1 px, the caption at its bottom, and no text wrapping, then situation is normal (it's how it's coded for, and is displayed when I edit/preview the subsection). Currently I see it aligned to the left, with no border, the caption at its top, and text wrapped in several cells (that's how I see it when I edit/preview the whole page, and save it).

About DMT "occurring" in the brain via blood transport, well, 1) that's not how Wallach worded it, 2) it may sound logical but the statement would nonetheless remain a hypothesis and not something "accepted" by the scientific community (that's how authors of the 2005 study present it, a hypothesis, to explain their finding of DMT in rat brain), and 3) the main problem is that it can hardly be said that we have reliable, robust evidence that DMT "occurs" in human blood, hence is transported by it: The 2005 study found absolutely no trace of DMT in human blood despite using the most sensitive and selective analytical method ever used to do the job (it's 12 to 200 times more sensitive, and much more selective (thanks to a preparative HPLC purification step), than those used in the 1970s). And older studies didn't yield consistent results either.

Robust evidence of DMT occurrence in CSF (i.e. a replication of Smythies et al. 1979 findings with a modern method like the one of the 2005 study) would be a more direct and less fragile piece of evidence (significant levels of INMT mRNA were found in the spinal cord) that DMT can "occur" in human brain.

As to Strassman... well, if on the one hand he was indeed careful not to present his hypothesis of DMT production in the pineal gland as a proven fact, on the other hand what he presented as credible bases for it, and how he worded this passage (his "methyltransferases" mumbo jumbo, p. 69), clearly is a gross misrepresentation of the facts available when he wrote his book, and verges on myth. --Doctorcito 03:53, 15 November 2010 (UTC) —Preceding unsigned comment added by Doctorcito (talk • contribs)

Done! --Doctorcito (talk) 18:31, 15 November 2010 (UTC)

The rabbit is going to fall asleep on the sofa after eating a large turkey dinner, not have psychedelic hallucinations. The referenced articles only address conversion of tryptamine to dimethyltryptamine. Your most recent reference from Thompson (1999) concludes, “However, the functional role of INMT in vivo remains unclear. Even though this enzyme was originally discovered as a result of interest in the possible generation of methylated metabolites of tryptamine and serotonin that might be psychoactive, our observations make that possibility less likely.” This does not validate Mandel’s earlier work. Why would Mandel use non-radioactive N-methyltryptamine when he had access to C14 N-methyltryptamine? Look, I know your trying to justify (or cover-up) why GC/MS shows DMT in the urine of non-drug users. But biosynthesis is not the answer. People are consuming DMT in the food additive Gum Arabic or Acacia gum. Please refer to the “Dangers” section, dated 11/23/2010 for further details. Suggest renaming this section to “Plant Biosynthesis”. Would be interested in references and details on how plants biosynthesis DMT. ----Raypurdy (talk) 13:28, 23 November 2010 (UTC)

I reverted your edit referred to above. Your assertion that "Many processed sugar products contain Gum Arabic where science has identified DMT as a biochemical cause for cancer" is simply fallacious. Further, your claim that certain alcoholic drinks don't simply make people drunk through alcohol, but rather through causing in them a serotonin syndrome due to DMT contained in gum arabic found in those drinks is ludicrous. --Pontificalibus (talk) 21:27, 23 November 2010 (UTC)

Can you (Raypurdy) please rephrase this clearly as I find it rather confusing. And please have the decency to avoid speculating about my intentions. A biosynthetic pathway for DMT in mammals has been repeatedly and consistently demonstrated since Axelrod's seminal study. The conclusion of Thompson et al. (1999) you cited has been discussed since then, notably by Jacob & Presti (2008) who noted that:

"the meaning of Km values, especially for in vivo biochemical pathways, is still open to interpretation. Although Thompson et al. argue that high Km values signify an enzyme–substrate combination that is not biologically meaningful, a meta-analysis of recent research has shown that high Km values are significant in biological systems".

I am going to undo your first edit in the article as it made baseless changes (edit: Pontificalibus apparently already did it - Edit#2: only the second was undone): I did clearly explain in the "Biosynthesis" first part that I was detailing lines of scientific research on endogenous DMT in mammals (not only humans). Hence the "Endogenous DMT" title of the subsection summarizing studies that explicitly looked for endogenous DMT in mammals (and found some, thus plainly justifying the title. Not all humans do eat "Gum Arabic or Acacia gum" (you'll have to provide credible citations showing that DMT has been detected in those products). Nor rats and rabbits do). This is not about danger or not danger, this is about presenting scientific research and data about a particular aspect of research on DMT. Furthermore your edit did also suppress other corrections I made in other sections, unrelated to your apparent point: An improved reference to Strassman's book, and rephrasing of the presentation of his hypothesis of pineal DMT.

You wrote in this edit that "Without a MAOI, the body quickly metabolizes orally administered DMT, and it therefore has no hallucinogenic effect unless the dose exceeds monoamine oxidase's metabolic capacity." Makes sense, but you are aware that oral doses up to 12 fold the mean fully psychedelic intramuscular one were determined to be inactive in a published study, aren't you? --Doctorcito (talk) 22:05, 23 November 2010 (UTC) You can of course reinstate this phrase with a normal, simple edit. No need to revert. --Doctorcito (talk) 23:25, 23 November 2010 (UTC)

Deleted Thompson (1999) reference because their conclusion does not support biosynthesis. Insert Jacob & Presti (2008) as a reference if they duplicated Thompson’s 1999 work and proved biosynthesis or Thompson’s retraction that his conclusion was wrong. Mandel reference should be deleted due to suspect procedures reflecting bias. Did Axelrod detection of DMT utilize GC/MS in 1961? Axelrod results also conflicts with DMT detection issues identified in the “Endogenous DMT” section. Neither, Mandel or Axelrod controlled all variables, namely that the test subjects were not exposed to DMT.

Biosynthesis is at best a hypothesis unless a quantitative relationship can be shown between tryptophan consumption and DMT levels. The number of people showing DMT in the table is more consistent with DMT/Acacia/Gum Arabic consumption than the tryptophan biosynthesis hypothesis. Most people eat tryptophan, so they should all show DMT, especially with the sensitivity improvements of LC-ESI-MS/MS. -- Raypurdy (talk) 12:08, 06 December 2010 (UTC)

Please stop editing content you clearly have no expert knowledge about (and check your talk page where the number of warnings should incite you to be more prudent).

I am not here to give you basic training in pharmacology, which you manifestly are lacking. All citations I did put in the article about biosynthesis do bring evidence supporting different aspects of DMT biosynthetic pathway, and some are reviews. Don't edit them because you believe to understand better (in fact what you just wrote means that you even didn't properly read or understood the content of this section: "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 don't require to be as sensitive as those needed to directly detect and quantify the minute amounts of endogenously formed DMT"). --Doctorcito (talk) 01:44, 7 December 2010 (UTC)

I’m unable to find a single reference that has tested a relationship between tryptophan and DMT. Piecing research papers together to draw a conclusion is original research. . Endogeneous DMT from tryptophan is therefore unproven. All that can be said is that DMT is occasionally found in mammals but we don’t know how it ultimately got there. If this reference doesn’t exist then biosynthesis and endogeneous DMT content will need to be removed.-- Raypurdy (talk) 11:09, 20 December 2010 (UTC)

Again, no one is here to teach you basic biochemistry. Please go learn the basics of tryptophan metabolism (this interactive graph might be a good start). And please stop this kind of ignorance-based threat of edition. --Doctorcito (talk) 19:18, 20 December 2010 (UTC)

Problems with the pharmacokinetic data in humans

In order to improve the "Pharmacology" section according to the Project Pharmacology Guideline, I re-read it carefully before any modification and noticed that there is a couple of problems with the pharmacokinetic data in humans brought by Nvcozzi (talk):

Questionable use of data from ayahuasca studies

The 3 references from which those data are excerpted are studies on ayahuasca or freeze-dried ayahuasca, not on DMT proper. It is highly questionable if not incorrect to put in an article on DMT pharmacokinetic data from studies where DMT is mixed with a cocktail of potent β-carbolines. Notably the apparent volume of distribution (V_d): It is extremely highly likely that, among other potential confounding variables, the known vasorelaxant actions of these β-carbolines (see refs below) modifie DMT V_d.

The volume of distribution of drugs, including DMT, is not affected by vascular tone. The main factors affecting Vd and their effects are as follows:

• uremia, burn patients, liver dysfunction → ↓ albumin binding → ↑ Vd
• pregnancy, ascites, edema → ↓ plasma concentration → ↑ Vd
• dehydration → ↑ plasma concentration → ↓ Vd
• heart failure, end-stage renal disease → ↓ clearance of drugs excreted by kidney, variable effects on Vd depending on drug.

The data obtained from the papers cited clearly demonstrate that DMT administered peripherally is accumulated into tissues, including brain tissue. The absolute plasma or blood concentrations alone are not predictive of the brain concentrations. The only reasonable access to human brain concentrations is via the apparent volume of distribution. The DMT Vd data obtained from ayahuasca studies is not likely to differ significantly from DMT given intravenously, and it is the best data available at present. Note that the active blood concentrations exhibit a wide range, and the Vd will also exhibit a range depending on which data one uses. Therefore the Vd for DMT is in the approximately 35-55 L/kg range and this will not change except under the conditions I listed above.

--User:nvcozzi(talk) 00:26, 19 January 2011 (UTC)

Thank you for the reply. You are right that β-carboline-induced vasorelaxation was not the best argument under the sun to question insertion of V_d values from Callaway et al., and Riba et al. studies.

The gist of the argument is elsewhere (it is just much longer to write):

The Wikipedia DMT article is about, well, DMT, i.e. pure DMT, not about ayahuasca or freeze-dried gel-capped ayahuasca.

OK, point taken.Nvcozzi (talk) 18:34, 24 January 2011 (UTC)

And pure DMT is either injected (IM or IV in clinical research settings), or inhaled (in other settings). So pure DMT proper V_d values would be relevant, i.e. those calculated after intravenous (IV) dosing.

Yet Callaway et al. (1999), and Riba et al. (2003) gave respectively V_ss/F, and V_z/F values, i.e. figures for DMT oral apparent volume of distribution (V_d), and furthermore when mixed with β-carbolines which pharmacology is rich and complex (both kinetics and dynamics).

Right, but that's why they reported V_d/F; they divided V_d by F (bioavailability) to account for the lower apparent V_d obtained from oral administration. F, if I recall, was ~ 0.50 (i.e. bioavailability ~ 50%). This commonly used approach normalizes the V_d. It takes into account all other variables for the route of administration (in this case oral) e.g. the presence of beta-carbolines, incomplete intestinal absorption, metabolism by nonMAO routes, etc. The V_d/F should be very close to the V_d obtained from IV data.Nvcozzi (talk) 18:34, 24 January 2011 (UTC)

Drug-drug interactions resulting in change in the volume of distribution of one of them is not unheard of (e.g. penbutolol increases lidocaine volume of distribution). These differences (oral V_d vs. proper V_d, with or without β-carbolines) do matter:

• Even if pure DMT oral absolute bioavailability has never been formally determined in humans (AFAIK), it is expected to be very low (oral doses up to 10 fold the plainly psychedelic 35 mg intramuscular one were determined to be without noticeable effects), due to extensive intestinal and hepatic (first-pass) metabolism.

Agree.Nvcozzi (talk) 18:34, 24 January 2011 (UTC)

Consequently, without the β-carbolines the 36-57 mg range of average DMT doses ingested in Callaway et al., and Riba et al. studies may well have resulted in null V_d figures because DMT would have been completely metabolized before reaching systemic circulation.

Agree. It would be as if no DMT was given at all → V_d = 0Nvcozzi (talk) 18:34, 24 January 2011 (UTC)

The difference with V_d calculated from IV injection (or from IM injections of the exactly same range of doses) would then be aptly characterized as 'extremey highly' significant.

In other words, it is glaringly obvious that ayahuasca β-carbolines do influence DMT oral V_d (and pharmacokinetics more generally).

Glaringly!  ;-) Nvcozzi (talk) 18:34, 24 January 2011 (UTC)

• Another evidence is provided by a comparison of the range of blood concentrations between injections of pure DMT, and ingestion of standard ayahuasca tea. In the case of injections (IM and IV) range is indeed wide, with max and min blood concentration values differing by a factor of 6.4 (IV) to ≈11 (IM). In contrast, with ayahuasca the range is much narrower: Plasma levels max/min ratio is only 2.2 in Callaway et al. (1996) (ranges of plasma levels aren't indicated in Riba et al. papers).
• Still another evidence, and a hard one, is Riba et al. (2003) finding of a statistically significant difference in oral V_d values between the low and high doses of their freeze-dried gel-capped ayahuasca; a result they interpreted as a nonlinear increase of DMT plasma levels, and bioavailability, with the high dose.

It is thus very likely that DMT oral V_d values from ayahuasca and freeze-dried gel-capped ayahuasca studies do significantly differ from proper V_d figures computed from DMT IV administration study.

I'm not in complete agreement with this. To be sure, the V_d calculated from IV dosing is the "gold standard", because F (bioavailability) is by definition "1" for drugs given IV, i.e. V_d/F = V_d. However, the whole point of dividing by F is to normalize so that one can derive an accurate V_d from various routes in the absence of IV administration. I will concede that, due to physiological complexities, the V_d/F for various routes is probably never exactly equal to V_d from IV calculations, but I contend that it will be "close".Nvcozzi (talk) 18:34, 24 January 2011 (UTC)

I do fully agree that V_d would be a good predictor of DMT brain concentration, and that published pharmacokinetic data on pure DMT aren't informative in this respect (incidentally, Rick Strassman may possibly still have the raw data of his study, which could be used to compute V_d and other interesting pharmacokinetic parameters). But I do maintain that it is questionable to include V_d values from Callaway et al., and Riba et al. studies to fill the void. Mentioning that oral V_d figures from these studies are suggestive of DMT concentration in brain, without actually citing the figures, could be a possibility. --Doctorcito (talk) 18:32, 21 January 2011 (UTC)

Moreover, there are a couple of human studies on pure DMT reporting blood or plasma levels after intramuscular or intravenous administration (I'll cite them). Unfortunately, there were no other pharmacokinetic data in these studies. Not a reason to use those on ayahuasca to fill the void.

Refs on vasorelaxant actions of β-carbolines that are present in ayahuasca:

• Berrougui et al. (2006) "Vasorelaxant effects of harmine and harmaline extracted from Peganum harmala L. seed's in isolated rat aorta". Pharmacological Research, 54(2): 150-7.
• Shi CC et al. (2001) "Comparative study on the vasorelaxant effects of three harmala alkaloids in vitro". Japanese Journal of Pharmacology,85(3):299-305. —Preceding unsigned comment added by Doctorcito (talk • contribs) 01:18, 20 November 2010 (UTC)

Refs on DMT blood and plasma levels after im and iv administration, respectively:

• Kaplan J et al. (1974)"Blood and urine levels of N,N-dimethyltryptamine following administration of psychoactive dosages to human subjects". Psychopharmacologia 38(3):239-45.
• Strassman RJ & Qualls CR (1994) "Dose-response study of N,N-dimethyltryptamine in humans. I. Neuroendocrine, autonomic, and cardiovascular effects". Archives of General Psychiatry 51(2):85-97.

--Doctorcito (talk) 14:46, 20 November 2010 (UTC)

Irrelevant comparison with synaptic dopamine concentration

Nvcozzi (talk) wrote:

Similar active uptake processes in human brain may plausibly concentrate DMT within neurons by several-fold or more, resulting in local concentrations in the micromolar or higher range. Interestingly, the concentrations of DMT required to occupy a significant fraction of any of its known receptor binding sites are between 1,000 and 1,000,000-fold lower than the calculated synaptic concentration of other neurotransmitters. For example, using amperometric measurements, the synaptic concentration of dopamine was estimated to reach about 75 mM.

This is not unlike comparing mass of apples contained in a 1 L bag to mass of oranges used to make 1 L of juice concentrate: Studies measuring blood or plasma levels in humans, and studies evidencing DMT accumulation in rat brain (e.g. in cortex) give concentrations for tissues where the cited estimation of dopamine (DA) concentration is about DA release from vesicles into synaptic cleft. Spatial/volume scales are here several orders of magnitude apart. Furthermore, as DMT dominant pharmacodynamic action is attributed to interaction with serotonin 2A receptor subtypes, comparison with serotonin (5-HT) concentrations would be more relevant. 'Interestingly', 5-HT tissue concentrations in various brain regions have been consistently determined to be in the 1.5-4 μM range. Unsurprisingly these concentration values are pretty close to those of DMT measured in blood and plasma levels in humans after i.m or i.v. administration of fully psychedelic doses; even without postulating an active transport mechanism through the blood brain barrier and concentration in brain. Taking into account such a highly plausible mechanism would mean that brain average concentrations of DMT after fully psychedelic dosing can be higher than those of serotonin. --Doctorcito (talk) 15:03, 23 November 2010 (UTC)

More problems with this passage: It is reproduced without attribution

Compare:

In humans, effective hallucinogenic doses produce peak DMT plasma concentrations ranging between 12 and 90 µg/L and with an apparent volume of distribution of 36 to 55 L.

The corresponding average molar plasma concentration of DMT is therefore in the range of 0.060–0.500 µM. However, the relatively high volume of distribution of DMT indicates significant movement of the drug from plasma into tissues and several reports have described the active accumulation of DMT and other tryptamines into rat brain following peripheral administration. Similar active uptake processes in human brain may plausibly concentrate DMT within neurons by several-fold or more, resulting in local concentrations in the micromolar or higher range.

-Nvcozzi (talk)

To this passage from Nicholas V. Cozzi et al. (2009) "Dimethyltryptamine and other hallucinogenic tryptamines exhibit substrate behavior at the serotonin uptake transporter and the vesicle monoamine transporter" Journal of Neural Transmission 116 (12), p. 1597:

In humans, effective hallucinogenic doses produce peak DMT plasma concentrations ranging between 12 and 90 μg/L and with an apparent volume of distribution of 36–55 L/kg (Callaway et al. 1999; Riba et al. 2003; Yritia et al. 2002). The corresponding molar plasma concentrations of DMT are in the range of 0.060–0.500 μM and this range is lower than the K_I values that were derived in the present study.

However, the relatively high volume of distribution of DMT indicates significant movement of the drug from plasma into tissues and several reports have described the active accumulation of DMT and other tryptamines

into rat brain following peripheral administration (Barker et al. 1982; Sangiah et al. 1979; Sitaram et al. 1987; Takahashi et al. 1985; Yanai et al. 1986). Similar active uptake processes in humans may plausibly concentrate DMT by severalfold or more, resulting in micromolar concentrations in the brain.

A possibility is that contributor Nvcozzi (talk) is one of the authors of this paper, which would be both great and not so good news:

• Great to have another member of the psychedelic research community contributing
• Not so good to see what could be considered self-plagiarism (from a copyrighted source, but fair use is in order here), and questionable utilization of ayahuasca pharmacokinetic data (see above).

Discussion with Nvcozzi (talk) is warranted... --Doctorcito (talk) 12:30, 20 November 2010 (UTC)

Additional problem, this time with pharmacodynamics

Here's the first assertion about DMT pharmacodynamics:

DMT acts as a non-selective agonist at most or all of the serotonin receptors (including 5-HT_2A and 5-HT_2C),

I've checked theses sources and more: If taken together they show that DMT has roughly comparable binding affinity at "most" (not "all") serotonin receptors, its efficacy as an agonist has been evaluated only at 3 serotonin receptor subtypes (5-HT_1A, 5-HT_2A and 5-HT_2C). The quoted assertion is thus erroneous, probably stemming from a basic confusion between affinity and efficacy. --Doctorcito (talk) 01:04, 26 November 2010 (UTC)

DMT is a qualitative agonist of 5-HT7 based on Ray TS (2010) Psychedelics and the Human Receptorome when it’s stated that DMT “is the only drug to have its best hit at the 5-HT7 receptor”. It also explains my calcinosis cutis from handling DMT and calcium found in Acacia. Quantitative determination of efficacy is TBD. -- Raypurdy (talk) 11:04, 06 December 2010 (UTC)

Please stop editing content you manifestly have no expert knowledge about (there is nothing as "qualitative" agonist). In Ray's study only affinity was determined at 5-HT7 receptor, and activity (i.e. efficacy) was evaluated only at 5-HT_2A and 5-HT_2C receptors. No one is here to provide you with basic training in pharmacology, which you are clearly lacking, so please stop your disruptive edits. --Doctorcito (talk) 02:01, 7 December 2010 (UTC)

Doctorcito has misrepresented a reference. The reference "Dimethyltryptamine and other hallucinogenic tryptamines exhibit substrate behavior at the serotonin uptake transporter and the vesicle monoamine transporter" (2009), found that “All of the tryptamines tested inhibited 5-HT uptake via SERT and VMAT2…”. The author noted a different finding with Nagai (2007), showing serotonin release, and speculated the difference that Nagai, “studied 5-HT uptake and release in rat brain synaptosomes, while we used human platelets …”. Medical studies have shown that changes in serotonin transporter metabolism appear to be associated with many different phenomena, including alcoholism, clinical depression, obsessive-compulsive disorder (OCD), romantic love, hypertension and generalized social phobia. -- Raypurdy (talk) 12:45, 16 December 2010 (UTC)

Are you conscious that you are ridiculing yourself in attributing to me what was originally written by contributor Nvcozzi, as anyone can verify with the history? I'll check this edit of yours later.

As to your other edit, changing the wording of DMT being hypothesized to shown to be an endogenous ligand for σ₁ receptors (something also brought by Nvcozzi, BTW), you've just demonstrated one more time that you don't properly understand what you read: The huge differences in DMT concentrations between those determined to activate σ₁ receptor, and those measured thus far in mammalian organisms preclude this to be anything else than a hypothesis (and moreover a not very plausible one). There is no mention of any measurement of endogenous DMT in the Fontanilla et al. paper. Doctorcito (talk) 23:57, 18 December 2010 (UTC)

OK, I've carefully read Cozzi et al. (2009) and Nagai et al. (2007) in order to check Raypurdy's edit on transporters (a content originally brought by Nvcozzi). Despite Raypurdy displayed one more time a lack of proper understanding (manifestly ignoring that a substance may be both a serotonin uptake inhibitor and a serotonin releaser, and that as Cozzi et al. did not assay serotonin release their study couldn't contradict any results on DMT as a releaser), the edit may be justified on other grounds: While Nagai et al. 2007 showed that, among 7 tested substituted tryptamines, α-metyltryptamine was a relatively potent serotonin releaser and uptake inhibitor, they didn't test DMT. Now Cozzi et al. used this result to suggest in passing that DMT is a "potential" serotonin releaser. I'm unsure such fragile and peripheral a hypothesis is worth mentioning.

Taking all this into account, the passage on transporters has been reworded and more precisions added. --Doctorcito (talk) 16:41, 21 December 2010 (UTC)

Please, no original research. Just capture the reference. Please excuse the editor owning mistake. I should have checked. -- Raypurdy (talk) 11:00, 20 December 2010 (UTC)

There is ample evidence in this discussion page and in the history of the article of your deliberate attempts to make uninformed and disruptive edits. Despite multiple warnings you are continuing. It may then be considered vandalism.

This edit of yours just add evidence: There is no original research when reporting what has been presented as a hypothesis in a couple of peer-reviewed papers, together with reliable and sourced data directly related to this hypothesis (and already discussed, at least partially, in two papers). No unpublished original conclusion is drawn, nor are they commented in an original way. --Doctorcito (talk) 17:55, 20 December 2010 (UTC)

Improvement of the article step by step: A better breakdown

To pursue improvement of the article, a step will be better adherence to Project Pharmacology Guideline. I thus plan to create a "History" section right after the Intro, and break down the "Pharmacology" section into "Pharmacokinetics" and "Pharmacodynamics". Existing content will be adapted accordingly, and improved where necessary (notably considering previous section on pharmacokinetic data). --Doctorcito (talk) 17:36, 22 November 2010 (UTC)

Done. Can of course be improved, but hopefully it is already an improvement, and will facilitate future edits. --Doctorcito (talk) 02:25, 29 November 2010 (UTC)

On the content of Franzen & Gross paper (1965)

On 18 January 2011, the following edit was made about the content of Franzen & Gross paper (1965):

"However, this report is often inaccurately interpreted as being evidence of N,N-DMT in the human body, for whatever reason, even though the report clearly states in the abstract, "There is no information about an occurrence of N,N-dimethyltryptamine in human beings."

I have a copy of Franzen & Gross paper (which, incidentally, is a very short one). It is obvious that a misunderstanding misleading abstract was at the base of the above-cited edit (Edit: I just watched the "abstract" and I understand how it can easily mislead a reader. I've never seen an abstract so confusing and badly made). The statement "There is no information about an occurrence of N,N-dimethyltryptamine in human beings" is located in the introduction-review part of the paper, i.e. it is a statement about the situation before Franzen & Gross study. After this introduction-review part, they do present their results, which unambiguously suggest "occurrence of N,N-dimethyltryptamine in human beings":

"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."

This should suffice to explain why the edit has been reverted. --Doctorcito (talk) 17:00, 18 January 2011 (UTC)

Aha, thanks. I don't have the full article so it really sucks trying to figure this out. I'll add that quote to the actual citation. --Notmyhandle (talk) 23:38, 18 January 2011 (UTC)

Ingredient in Polyester?

Is this the same as the polyester ingredient? If so, please create a section, if not we should have a disambiguation page that links it to the proper DMT Mstefaniak (talk) 08:31, 3 March 2011 (UTC)

That's Dimethylterephthalate. --Notmyhandle (talk) 08:33, 3 March 2011 (UTC)

Actually Dimethyl terephthalate I do not know how to create the reference, "for the chemical see Dimethyl terephthalate" Mstefaniak (talk) 08:57, 3 March 2011 (UTC)

If you type "DMT" in Wikipedia's search you end up at DMT which is the disambiguation page listing Dimethyl terephthalate and Dimethyltryptamine. People who end up here via search instead of at DMT are unlikely to want Dimethyl terephthalate.--Pontificalibus (talk) 09:00, 3 March 2011 (UTC)

re: Dimethyltryptamine origin

I suggest that someone who knows something about this subject visit Dimethyltryptamine origin and take from that article anything that can improve this one, then replace that page with a redirect. I don't know the first thing about this topic, so that's why I didn't do so myself. Thanks! --Mblumber (talk) 02:10, 15 June 2011 (UTC)

Thanks for the info. I'll check this new page and report on its discussion page. --Doctorcito (talk) 18:39, 16 June 2011 (UTC)

Most of that stuff is speculation - unproven hypotheses of Rick Strassman and the resulting urban myths surrounding the mysteries of the chemical and its subjective psychoactive effects. This article could discuss beliefs surrounding the pineal gland, but it seems unnecessary. --Notmyhandle (talk) 19:06, 18 June 2011 (UTC)