Mysterious tryptamines





One of the strongest hallucinogenic drugs is N,N-dimethyltryptamine, known colloquially as DMT, which has a similar action to psilocybin but acts over a shorter time scale. So, it might come as a surprise that DMT and two related tryptamines also exist naturally in the human body, having been detected in blood, urine and cerebrospinal fluid.

No-one knows what DMT does or why it is there. Some scientists have speculated that it might have a link to psychosis but there is no proof to support that. The enzyme which produces DMT in the body, indole-N-methyltransferase, has been found in the pineal gland, in motor neurons in the spinal cord, and in the retina, but DMT has not, prolonging the mystery about its function.

In an effort to simplify the location of DMT, scientists in the US have developed a method that can measure DMT itself, as well as 22 related amines. They were selected because they are known to be metabolites of tryptophan or are involved in the metabolic pathways of the three known DMTs.

The procedure was designed for in vivo measurements and illustrated by analysing the microdialysate from the pineal glands in living rats. It was described in Biomedical Chromatography by Steven Barker and colleagues from Louisiana State University, Baton Rouge, the University of Michigan Medical School, Ann Arbor, the University of New Mexico School of Medicine, Albuquerque, and Cottonwood Research Foundation, Gallup, New Mexico.

Pineal gland flush

Rats were fitted with a microdialysis probe that was flushed with artificial cerebrospinal fluid. After collection, deuterated 5-methoxy-DMT was added as an internal standard and the solution was analysed directly. No further preparation was needed, not even dilution of the samples.

They were analysed directly by LC-tandem-MS, using a C 18 column to separate the compounds which all had retention times between 5 and 8.5 minutes. Most of the peaks were resolved but those that showed some degree of overlap were resolved fully by a combination of the retention time and the ions that were monitored.

The 24 compounds were measured by multiple reaction monitoring, using the protonated molecules as the precursor ions and various characteristic ions as product ions. The identification of the compounds was supported by high-resolution mass spectrometry measurements which nailed down the exact compositions of each ion.

Limits of detection in the range 0.02-2.0 ng/mL were achieved and the other analytical data indicated that the method was reliable and sensitive for the target group of compounds.

Endogenous hallucinogens

A total of eight compounds were detected in the microdialysate from the pineal gland, including DMT itself. This is the first time that DMT has been found in the pineal glands of live animals.

Those samples that contained DMT also contained its precursor, tryptamine, and the final compound in its metabolic pathway, indole-3-acetic acid. The co-presence of all three compounds lends support to the presence of DMT itself, backed up the retention time and the high-resolution mass measurements.

The other compounds that were found were melatonin and 5-hydroxytryptamine, which were expected in the pineal gland, as well as tryptophan, 5-hydroxyindole-3-acetic acid and 5-hydroxy-N-acetyltryptamine. However, the absence of other compounds related to DMT should not be taken as conclusive evidence at this stage. As the researchers pointed out, dialysis was carried out for just 2 hours. Longer studies incorporating circadian changes could flush out more of the target group.

The method will be suitable for further studies on endogenous hallucinogens in other parts of the brain and in biological fluids from other parts of the body. Its good detection limits and specificity will allow the simultaneous analysis of many compounds related to tryptophan and will help to develop a better understanding of the role of these natural hallucinogens.

Related Links Biomedical Chromatography 2013 (Article in Press): "LC/MS/MS analysis of the endogenous dimethyltryptamine hallucinogens, their precursors, and major metabolites in rat pineal gland microdialysate" Article by Steve Down Read more about Steve and our other columnists >>> The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.

Author(s)

Steve Down