DMT Update 2012

One of our primary research projects has been the development of a new methodology to measure endogenous DMT, 5-methoxy-DMT (5-methoxy-DMT), and bufotenine, as well as relevant precursors and metabolic breakdown products using state-of-the-art liquid chromatography-mass spectrometry (LC/MS) equipment. It gives us great pleasure to announce that the goals of this project, thanks to our generous donors and collaborators, have been completed.

The new method, developed by Steven Barker, Ph.D. (Vice-President of Cottonwood Research Foundation), his graduate student Ethan McIlHenny (School of Veterinary Medicine, Louisiana State University, Baton Rouge Louisiana) and Rick Strassman, M.D. (President of Cottonwood Research Foundation), can be employed to measure the three known endogenous hallucinogens and their major N-oxide metabolites in blood, urine, cerebrospinal fluid, ocular fluid and/or other tissues. The method uses advanced LC/MS/MS technology and a simple sample preparation step that permits unequivocal identification of the compounds and detection at less than 1 picogram/ml (one billionth of a gram per milliliter).

Early investigations into the role of endogenous tryptamine hallucinogens in humans did not have at their disposal methods sensitive and specific enough to unequivocally measure the parent hallucinogens at their apparent very low levels, particularly in blood. Additionally, all such studies had previously ignored the importance of the levels of their metabolites, information that has proven to be necessary to fully assess the status of an endogenous hallucinogen pathway. This new methodology provides an improvement over previous assay sensitivity by at least ten to one thousand-fold, provides confirmation of structural identity, and finally provides information on a major metabolite (the N-oxide) that has never before been monitored in any endogenous hallucinogen study in humans. We presently have a review of the search for endogenous hallucinogens in press (1).

Advances in the method and a better understanding of DMT metabolism were gained through our research on ayahuasca (2-4). Studies were conducted with Dr. Jordi Riba (Drug Research Center, Hospital de Sant Pau, Autonomous of Barcelona), whose team has been the first to study ayahuasca in a clinical research setting. The analyses have shown a major metabolite of DMT, DMT-N-oxide (which retains the identifying structure of the parent substance), being excreted in the urine at levels 10-20 times greater than DMT itself after ayahuasca administration. Similarly, N-oxide levels in blood were four times greater than DMT. This is the first time this metabolite has been reported in humans following DMT administration by any route. All previous studies that attempted to measure DMT in blood and/or urine failed to measure this compound and thus may have missed significant additional evidence for the presence of DMT. Data suggest that similar results will also occur for the endogenous hallucinogens bufotenine and 5-methoxy-DMT and that measurement of their N-oxide metabolites will also greatly enhance our ability to determine the normal role and function of these compounds.

This methodology must now be applied to determine the potential role of these compounds in non-drug induced altered states of consciousness with psychedelic features, such as dreams, psychosis, meditation, religious experience, childbirth, and near-death states and we are very eager to do so. This effort has been made even more important following the recent discoveries of Cozzi et al. (5) that the enzyme responsible for synthesis of the endogenous hallucinogens is present in pineal gland, brain, spinal cord and retinal tissues of primates and appears to be an inducible enzyme, an enzyme that responds to specific signals. Therefore, clearly establishing the role of endogenous tryptamine hallucinogens in various states of consciousness will provide tremendous insight into their origin, and may lead to more reliable means of working with and studying their utility.

With necessary additional funding from our contributors, we anticipate that we will be able to begin the pursuit of the answer to the question , “What is the role of endogenous hallucinogens in humans?” and the many other questions their presence raises.

1. S. A. Barker, Ethan H. McIlhenny, Rick Strassman, 2012,  A Critical Review of Reports of Endogenous Psychedelic N, N-Dimethyltryptamines in Humans: 1955-2010, Drug Testing and Analysis, in press (invited paper in Special Issue on Psychedelic Drugs).

2. Jordi Riba, Ethan H. McIlhenny, Marta Valle, José Carlos Bouso S. A. Barker, 2012, Metabolism and disposition of N,N-dimethyltryptamine and harmala alkaloids after oral administration of ayahuasca, Drug Testing and Analysis, submitted (invited paper in Special Issue on Psychedelic Drugs)

3. Ethan H. McIlhenny, Jordi Riba, Manel J. Barbanoj, Rick Strassman, and S.A. Barker, 2012, Methodology for the Determination of Ayahuasca’s Major Constituents and Their Metabolites in Blood, Journal of Biomedical Chromatography, Published online 2011, Jun 28. doi: 10.1002/bmc.1657.

4. Ethan H. McIlhenny, Jordi Riba, Manel J. Barbanoj, Rick Strassman, and S.A. Barker, 2011, Methodology for and the Determination of the Major Constituents and Metabolites of the Amazonian Botanical Medicine Ayahuasca in Human Urine, J. Biomed. Chromatogr. 25, 970-984.

5. N. V. Cozzi, T. A. Mavlyutov, M. A. Thompson, A. E. Ruoho. Indolethylamine N-methyltransferase expression in primate nervous tissue. Soc. Neurosci. Abs. 2011, 37, 840.19 (2011)

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