One of our primary research projects, 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 Dr. Rick Strassman (President of Cottonwood Research Foundation), is the development of a new methodology to measure DMT, 5-methoxy-DMT, and bufotenine, as well as their precursors and metabolic breakdown products using state-of-the-art liquid chromatography-mass spectrometry (LC/MS) equipment. Previous investigations into the role of endogenous tryptamine hallucinogens in humans did not have at their disposal methods sensitive enough to measure the parent hallucinogens at their apparent very low levels, particularly in blood. Additionally, all such studies have previously ignored the importance of the levels of their precursors and metabolites, information that is necessary to fully assess the status of the endogenous hallucinogen pathway. This project provides an improvement over previous assay sensitivity by at least one thousand-fold and finally provides information on the entire pathway as a function of time and in health and disease. We have established a simple method to, at present, separate, identify and quantify 26 compounds simultaneously in a single blood or urine sample. Our current methodology provides us with the ability to prepare a blood or urine sample for analysis as small as 100 microliters in as little as ten minutes and complete the sample analysis in as little as twenty minutes, all at the sub-nanogram level for the compounds being examined. The method is currently undergoing further validation studies and we are continuing to examine ways to enhance overall assay sensitivity. The first application of the expanded, 26 compound method, examining all of the relevant compounds in the endogenous hallucinogen pathway, has been in urine samples obtained in a clinical trial in which known doses of ayahuasca were administered to healthy young volunteers. The study was conducted by 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, being excreted in the urine. This is the first time this metabolite has been reported in humans following DMT administration, although previous studies in rats and research conducted in tissues in vitro had suggested it would be present. What these data also show, however, is that all previous studies that attempted to measure DMT in urine failed to measure this compound and thus may have missed significant additional evidence for the presence of DMT. We believe 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. Similar measurements on blood samples from consumers of ayahuasca are also underway and new data that further enlighten us as to how best to detect and study these compounds is being obtained. In addition, we will determine levels in sleep, dreams, meditation, childbirth, and near-death states. Establishing the role of endogenous tryptamines in these states will provide tremendous insight into their origination, and may lead to more reliable means of working with and studying their utility. With additional funding from our contributors, we anticipate that it will take approximately a year to complete the development of the new assay, and establish normative values. Subsequent research into these compounds role in naturally occurring altered states, occurring in collaboration with research centers around the world, will be ongoing for many years. |
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