rational exploration of the underground

The amine group of tryptamine possesses a nitrogen with two hydrogens where functional groups can be substituted. Let’s start with the simple case where both of these substitutions are identical. The best known example is dimethyltryptamine, abbreviated as DMT (D for di meaning two, M for the methyl alkyl substitions, and T for the tryptamine backbone). There are other tryptamines like DMT with longer symmetrical alkyl chains which have similar effects and are named in a similar manner.

Some dialkylated tryptamines: dimethyltryptamine (DMT), diethyltryptamine (DET), dipropyltryptamine (DPT), dibutyltryptamine (DBT).

DMT is typically smoked as other consumption routes are ineffective due to MAO degradation, but the longer alkyl chains do not have this issue and are all orally active. There is no theoretical limit to the alkyl chain length, but potency decreases as chain length increases. DBT is the longest simple chain dialkylated tryptamine commonly bioassayed in man.

We can also consider asymmetrical cases where the two substitutions are different. The possible combinations quickly increase in number as the following table up to alkyl chains of three carbons in size illustrates. Asymmetric compounds are referred to by giving initials to both of their substitutions (shortest chain first) and ending with a T to signify the tryptamine backbone.

Linked compounds have a full entry in TiHKAL.

These two rulesets for symmetric and asymmetric substitutions allow us to refer to a huge variety of n-alkylated tryptamines using abbreviations in a simple and consistent manner.

Shulgin, A. #2 DBT. Tryptamines I Have Known and Loved. Transform Press, 1997.

Biological organisms are wondrous little molecular factories, their enzyme catalyzed reactions often accomplishing in a single step what would confound a chemist in a well-stocked laboratory. Researchers have attempted to harness these biosynthetic pathways to create complex molecules not easily synthesized by conventional methods.

Psilocybin is produced via a biosynthetic grid where enzymes act on various closely related intermediate compounds in turn. The enzymes do not appear to be particularly picky about the compounds they modify. For instance, dimethyltryptamine (DMT) is hydroxylated to 4-HO-DMT naturally in psilocybin mushrooms. Other precursor compounds like tryptamine and methyltryptamine are also hydroxlyated to 4-hydroxy-tryptamine and 4-hydroxy-methyltryptamine respectively.

If an entirely new synthetic tryptamine of similar structure was introduced to these mushrooms, would the same enzymes act on it? This could produce a new and unique psychedelic compound where some of the heavy lifting of synthesis is accomplished by the biological expertise of the mushroom itself and not by conventional laboratory chemistry.

Jochen Gartz decided to attempt this by adding diethyltryptamine (DET, a close relative of DMT) to the fruiting body of psilocybe cubensis. He hoped that it would be hydroxylated to 4-HO-DET, or possibly phosphorylated even further to 4-PO-DET. He first colonized a mixture of cow dung and rice grain with psilocybe cubensis, and then injected it with a solution of DET. Within four weeks mushrooms were produced, and five total flushes of mushrooms were obtained.

all values % by weight of dry mushroom

The project was a success, with significant amounts of 4-HO-DET produced. No DET was found in the dried mushrooms. A mass balance was not conducted to determine the efficiency of the conversion and possible losses in the fruiting body itself. The demonstrated non-selectivity of the enzymes in psilocybe cubensis toward other tryptamine derivatives opened to the door to the possibility of producing truly exotic and difficult to synthesize compounds such as 4-HO-5-MeO-DMT.

Despite this little additional data is available on the tryptamine derivatives that are able to be substituted in the fruiting body and the repeatability of the experiment. Some have found little success, noting only a decrease in the size of the mushrooms produced. Other attempts have discovered perhaps a qualitative difference in potency and character of the psychedelic experience, but this has not been substantiated by quantitative measurement.

Biotransformation of tryptamine derivatives in mycelial cultures of Psilocybe. Gartz, J. Journal of Basic Microbiology, Volume 29, Issue 6, Pages 347-352 (1989).

One of the most popular “drug geek” myths is that the powerful psychedelic compound DMT is produced naturally within your body, specifically the pineal gland. Not only this, but this natural DMT is apparently involved in a wide variety of previously unexplained processes - it is the mechanism of dreaming, it causes religious feelings, and DMT production spikes near death to “carry away the soul”. This appears to stem primarily from Dr. Richard Strassman’s book The Spirit Molecule, which advanced many of these hypotheses which were then passed on and extrapolated telephone-game style to the point where fluoridated water is apparently an Illuminati plot to suppress natural DMT production.

There’s just one problem - there doesn’t appear to be any concrete evidence whatsoever for this. Dr. Strassman himself explains:

I did my best in the DMT book to differentiate between what is known, and what I was conjecturing about (based upon what is known), regarding certain aspects of DMT dynamics. However, it’s amazing how ineffective my efforts seem to have been. So many people write me, or write elsewhere, about DMT, and the pineal, assuming that the things I conjecture about are true. When I was writing the book, I thought I was clear enough, and repeating myself would have gotten tedious.

We don’t know whether DMT is made in the pineal. I muster a lot of circumstantial evidence supporting a reason to look long and hard at the pineal, but we do not yet know. There are data suggesting urinary DMT rises in psychotic patients when their psychosis is worse. However, we don’t know whether DMT rises during dreams, meditation, near-death, death, birth or any other endogenous altered state. To the extent those states resemble those brought on by giving DMT, it certainly makes one wonder if endogenous DMT might be involved, and if it were, it would explain a lot. But we don’t know yet. Even if the pineal weren’t involved, that would have little overall effect on my theories regarding a role for DMT in endogenous altered states, because we do know that the gene involved in DMT synthesis is present in many organs, particularly lung. If the pineal made DMT, it would tie up a lot of loose ends regarding this enigmatic little organ. But people seem to live pretty normals lives without a pineal gland; for example, when it has had to be removed because of a tumor.

In both these regards-the pineal-DMT connection, and endogenous DMT dynamics-we ought to know a lot more within the next several years due to the efforts of a research group being led by Steven Barker at Louisiana State University. He, with his grad student Ethan McIlhenny, are developing a new super-assay for DMT, 5-MeO-DMT, bufotenine, and metabolites. This assay will be capable of detecting those compounds much more sensitively than previous generations of assays. They’re looking at endogenous levels in awake sober normals, to assess baseline values of these compounds. We should have some data from those samples within a year. They also will be looking at pineal tissue. Once we have some baseline data in normal humans in normal waking consciousness, comparisons can be made between those levels and levels in endogenous altered states, like dreams, near-death, and so on.

It appears that myths about drugs can cut both ways, and this is an important illustration of the requirement for critical thinking, no matter how appealing the initial conjecture. Steven Barker and Ethan McIlhenny’s work to determine baseline DMT levels continues, with their latest paper involving detection of metabolites produced by ayahuasca consumption.

Hanna J. “DMT and the Pineal: Fact or Fiction?” www.erowid.org/chemicals/dmt/dmt_article2.shtml. Jun 3 2010.