“Myth,” “arguably bullshit,” and “deserving a decent burial.” These are some of the published statements by reputable scientists reacting to various claims made about DMT. Usually, these words are used to attack “pseudoscience,” the kiss of death for scientific theories that lack merit, are patently false, and objectively falsifiable. Several theories about DMT have aroused these strong reactions. In this week’s post, I suggest that some of these reactions are appropriate whereas others are not.

The psychedelic theory of schizophrenia’s decent burial, 1976

After DMT’s discovery in mammalian lung in the 1960s, psychiatric researchers sought a relationship between endogenous DMT and naturally-occurring psychoses, especially schizophrenia. To the extent that the psychological effects of DMT administration in normals resembled naturally-occurring psychotic symptoms, one could hypothesize that endogenous DMT was involved in those non-drug syndromes. Additional studies sought differences between normal and patients viz. DMT blood levels, and in metabolism of, or reactions to, the drug.

Chris Gillin was one of my most important mentors during my fellowship in clinical psychopharmacology research at UC San Diego in the early 1980s. A few years before, he published a paper in the flagship American Journal of Psychiatry, joined by several veteran NIH research colleague co-authors (https://www.researchgate.net/publication/22093265_The_psychedelic_model_of_schizophrenia_The_case_of_NN-dimethyltryptamine). Summarizing the data to date, Gillin concluded that a link between DMT and schizophrenia was weak, and unless new data were forthcoming, it was time to give the psychedelic theory of schizophrenia a “decent burial.”

By that time, DMT and other psychedelics had been placed into Schedule I. Cogent comparisons between natural psychosis and the DMT effect were in their infancy. In addition, assays for blood levels of DMT were not sensitive enough to reveal differences in blood levels between groups. Not to be underestimated was the stigma attached to human psychedelic drug research in the 1970s. Studying any role for any psychedelic in any human condition carried professional risk.

Human psychedelic drug administration studies had ceased years before, so his plea for a mercy killing had little practical impact. Nevertheless, such outright refutation of this line of inquiry by a group of NIH researchers couldn’t have encouraged many young investigators to pursue this line of research, even preclinical, or for more established ones to continue working in it.

The theory has not died, however, and recent advances in research methodology—as is the case in any scientific field—have breathed new life into it. For example, a German study several years ago (https://www.ncbi.nlm.nih.gov/pubmed/16342002) compared the effects of a continuous infusion of DMT with symptoms of schizophrenia. Additional advances in characterizing psychoses—parsing schizophrenic symptoms into negative and positive ones—provided other new tools which uncovered a relationship between positive symptoms and DMT’s effects.

Before leaving the DMT-psychosis theory, it’s important to mention that our understanding of the genetic regulation of DMT synthesis is advancing. We soon will be able to look for differences between normals and patients regarding DMT’s genetic regulation. This is the logical method to follow since blood levels are so difficult to measure.

Data, hypotheses, speculation

Not all claims about DMT’s effects have retained the luster of scientific respectability. Part of this is due to readers of my DMT book, both professional and lay, blurring the lines between data, data-based hypotheses, and theories that begin with data but venture further into metaphysical speculation.

Regarding data-based hypotheses, these are amenable to testing with generally available tools, and could be confirmed or refuted within a generation. One is the notion that the pineal gland contains DMT. Another is that DMT levels in brain rise during the dying process. The 1991 paper in which I first present these ideas ran 40 pages and cited 152 references, nearly all from the peer-reviewed biomedical literature. They were strong hypotheses then and remain strong now. For example, a 2013 publication confirmed DMT’s presence in the living rodent pineal gland (http://onlinelibrary.wiley.com/doi/10.1002/bmc.2981/abstract). And studies are now underway examining DMT brain levels in the dying animal. DMT’s protective effects on neurons exposed to hypoxia (https://www.frontiersin.org/articles/10.3389/fnins.2016.00423/full) is additional evidence supporting its “utility” in the dying animal.

In addition, the ability to breed and study knockout and knockdown animals that possess less or no activity of the DMT-synthesizing enzyme, INMT, will open a new era in understanding the role of endogenous DMT. What will those animals be like? And will replacing DMT reverse whatever changes are seen?

The myth of DMT

The bases for the recent use of “myth” in describing the notion that endogenous DMT—pineal and/or lung—plays a physiological role (http://journals.sagepub.com/doi/abs/10.1177/0269881117736919) is less clear than that of the NIH group’s use of “decent burial” in 1976. I say this because in 1976, DMT (and other psychedelic drug) research protocols were moribund. We had reached the limits of our technology and diagnostic systems, and were laboring under government and public backlash against psychedelic research.

Now, on the other hand, there is a resurgence of human psychedelic drug studies, and we are seeing increasing quality and quantity of human and preclinical data regarding DMT’s effects. This is no time to abandon DMT research; rather, it is a great opportunity to accelerate research, especially regarding its endogenous functions. As advances in research methodology accelerate, additional data-driven hypotheses such as DMT’s role in dreams, near-death states, and other naturally-occurring alterations in consciousness can be empirically tested.

Several arguments are brought to bear in calling the notion of a role for endogenous DMT in normal physiology a myth. One is that DMT is found in too low levels in pineal to have any role. This argument overlooks the over 50-year-old fact of lung synthesis of DMT, and the more than 30-year history of data demonstrating active transport of DMT into brain. A role for endogenous DMT in brain physiology doesn’t require that the pineal is its only source. This role belongs to the lung, and the brain actively transports blood-borne DMT into its confines. The likely intermittent production of DMT by the pineal, as opposed to the likely more regular production by the lung, is also supported by the lack of obvious differences between pinealectomized humans (as a result of a destructive tumor or stroke) and normals.

The “too low a level” argument also ignores anatomical factors. “Brain levels” or “blood levels” are not the same as “levels at critical sites.” The pineal hangs behind the third ventricle, which is filled with cerebrospinal fluid (CSF). By means of direct release of pineal DMT into CSF, critical sensory way-stations in the brain, in close proximity to and bathed in the same CSF, could be directly affected by extremely low levels.

The “DMT is broken down too quickly to exert an effect” argument is also refuted by data. The half-life of DMT is 3-6 minutes, not zero.

The “other compounds are more likely” notion makes sense and ought to be investigated. The first step would be to administer said compounds and compare their subjective effects to those of naturally-occurring altered states. I’m not wedded to DMT, or 5-methoxy-DMT, or any particular compound. However, I do believe that there are biological bases for unusual mental states, to say nothing of usual ones. So far, the most data support a role for DMT: it is a classical psychedelic with effects overlapping those of naturally-occurring altered states; found in the body; produced by lung and pineal; and receptors and brain circuitry relevant for its subjective effects are increasingly well-characterized.

Arguably bullshit

The less data-driven, more metaphysical, hypotheses have received this label (http://www.wired.co.uk/article/mapping-brain-dmt-psychedelic-drugs); in particular, the notion of the “transdimensional reality” of the DMT state. This meme, inspired by the strong reality sense of the DMT experience—especially that of so-called sentient autonomous beings—has drawn the most ire. (Close behind are my musings regarding the conflation of Tibetan Buddhist theories of the soul’s journey through the bardos with developmental human neuroendocrinology.) There clearly are no data supporting these ideas. However, explicating the brain areas mediating the experience of beings, for example, won’t necessarily refute notions of the externally existent nature of what is apprehended under the influence of a full dose of DMT. They may rather be evidence of the brain changes associated with and/or necessary for consciousness perceiving those previously invisible levels. More sophisticated experiments than those that simply point to photographs of brain images and state “This is where the (unreal) beings come from” are necessary.

More than most aspects of the DMT experience, that of the “beings” stirs up the most resistance from scientific researchers. However, acknowledging the phenomenon doesn’t require believing that they are transdimensional life forms. Rather, they are consistently described aspects of the high dose DMT state. We ought to study them using the tools of science now applied to any other striking subjective experience. Functional brain imaging, psychometrics, psychoanalysis, and theology could all bring to bear their tools in examining this intriguing phenomenon. That is, as long as any and all of these disciplines were applied using their own internally established rigorous methodologies, peer-review, and so on.

DMT as psychedelic research’s problem child

The episodic designation of DMT as pariah is unique within the psychedelic research community. We don’t hear the same kinds of visceral over-wrought name-calling in the case of LSD, mescaline, salvia, ketamine, psilocybin, even ayahuasca. It is as if DMT carries some stain. Perhaps its association with preliterate Indians from Latin America; or many early psychedelicists’ frightening initial experiences with it; or its initial psychiatric coming-out taking place behind the Iron Curtain in Communist Hungary.

Above all, however, is the likelihood that the full DMT effect causes to teeter too many of the sacred cows hurriedly being erected on the altars of contemporary biomedical research. These include:

1) The meme that all religions have at their core the mystical-unitive experience falls flat in the case of DMT, which provides the paradigmatic interactive-relational drug experience.

2) A full dose of DMT is less amenable to set, setting, and suggestion which are being fully, and beneficially, utilized in current studies—maximizing the placebo-enhancing effects of modest doses of drugs in highly-structured protocols. DMT effects are much less malleable.

3) No other psychedelic so reliably convinces the experient of the reality of what they are apprehending. This is in contrast to the usual sense, even on high doses of other drugs, that you are “on drugs” rather than “really someplace else.” While we may use DMT to study how we gauge the reality of any particular experience, the epistemological Pandora’s box that this might open could be grievously disruptive to the mainstream.

4) DMT’s endogenicity is unique and requires explication. What if DMT levels in brain rise at death? What if DMT regulates normal waking, particularly visual, consciousness? What if naturally-occurring psychosis is the result of disequilibrium of DMT dynamics? What happens when the DMT-synthesizing gene is silenced? Among other questions.

DMT will never go away

Literally, because it is an endogenous mammalian compound and is present in hundreds if not thousands of plants. Figuratively, because its intriguing and compelling effects touch upon so many fundamental human concerns: consciousness and the brain, dreams and dying, imagination and reality. It is not surprising that any single entity that crosses over into so many disparate disciplines arouses such powerful reactions. Anyone who decides to study DMT ought to expect an even more challenging path forward—being periodically assailed by one’s fellow researchers—than that associated with the more mainstream psychedelic projects now taking place.