2021 Interview with DMT Researcher Dr. Steven Barker

Dr. Steven Barker is one of the world’s foremost experts pertaining to endogenous DMT research. His undergraduate studies took place at the University of Alabama in Birmingham where he received his B.S., M.S., & Ph.D. in Chemistry/Neurochemistry. Dr. Barker’s research includes analytical toxicology, the Neurochemistry of hallucinogens, and has been extensively involved in studies involving the endogenously produced hormone dimethyltryptamine (DMT) since 1976. It had been nearly 6 years since we first interviewed Dr. Barker so an update was much needed.

–Begin Interview

JC: Can you confirm unequivocally that DMT has been found in the human brain?

Dr. Barker: The simple answer is No… and Yes. I have not personally confirmed the presence of DMT in human brain through any sample analysis on my part. I can confirm, however, that DMT was found in human CSF samples in 4 studies, as reported in my 2012 manuscript “A critical review of reports of endogenous psychedelic N, N-dimethyltryptamines in humans: 1955–2010” covering 69 studies reporting detection of DMT.

DMT: cerebrospinal fluid

• Of the 69 studies, 4 examined CSF for DMT.
• CSF samples from 136 individuals were examined for the
presence of DMT: 82 patients and 54 controls. Among
patients, 34 were positive for DMT (41%) and 48 were
negative. Among controls, 22 were positive (41%) and 32
were negative. Thus, 56 individuals were positive (41%)
and 80 were negative.

• Concentrations of DMT in CSF ranged from 0.12 to 100 ng/ml;

The presence of DMT was confirmed by GC/MS analyses using appropriate confirmation criteria. Such data are considered to be unequivocal.

This is as close as anyone has gotten to confirming DMT in human brain and you can, I’m sure, appreciate the difficulties of doing direct or tissue studies. Doing studies on humans is overtly complicated and doing brain perfusion like we did in rats to report the presence of DMT in freely moving, live rats would be practically impossible to do in humans. Post-mortem tissue analysis in humans is also complicated by the fact that data suggests that DMT may be rapidly degraded during the tissue collection process. We do believe that this is, in part, the reason for the success in doing perfusion studies. Similarly, the absence of degradative enzymes in CSF seems to have preserved the DMT for detection. However, the findings in CSF and the recent data by Dean et al. (2019) showing high concentrations of co-localized INMT and AADC, the two most important enzymes for the biosynthesis of DMT, in the choroid plexus underscores the early CSF findings. All of the rest is inferred. Indeed, neuroscience research and medicine more know about the rat than we do humans!

JC: Do you believe that rat studies reliably translate into human studies when it comes to neurochemistry? Have any notable differences been noted regarding rats producing compounds that humans do not?

Dr. Barker: A mouse is not a rat is not a human. However, they do share about 96-99% homology in genes. There are some differences in a very few pathways but, in this specific case, they do all have the same genes encoding for INMT and AADC as humans. All three have been shown to biosynthesize DMT (in vivo and/or in vitro) and this ability has also been observed in a number of other species as well. There may be differences but that may occur in absolute quantity, brain location, degree of regulation, etc. Are the data from mice or rats directly translatable to humans? Although more comparative research would help answer this, I do not think there is any doubt that the findings in rats and mice imply that we should consider that they are convergent with what we will eventually prove in humans.

Hope that answers the question! We always have to be careful in our direct implications of research findings in other species and what that means for humans.

JC: Prior to the finding by Dr. Dean that INMT & AADC were co-localized throughout various parts of the brain, there was speculative criticism that the pineal gland was incapable of producing sufficient amounts of DMT to cause any measurable effect or change in perception. Do you believe that the finding by Dr. Dean essentially supersedes the pineal gland debate to the point that it is clear that DMT is synthesized virtually throughout the entire brain?

Dr. Barker: What was interesting about the criticism was that it was delivered before we even knew what the levels of DMT were in rat brain. Furthermore, it was based on data related to dose administration intravenously that delivered a psychedelic effect and ignored completely that what we were now dealing with was DMT being naturally synthesized in specific areas of the brain. The very small volume of neuronal synapses permits the perceived small amount of any neurotransmitter to easily reach nano-micro-even milli-molar concentrations within the cleft. Acting in specific brain areas DMT could clearly exert a neurophysiological effect, from regulation of perception, dreaming, creativity and imagination, etc., and, under certain dramatic changes in physiological conditions, be sufficiently elevated to produce other altered states. Basic neurochemistry. The 2019 Dean et al. publication demonstrated that the “normal” level of DMT in the visual cortex of the rat was in the same range as serotonin, an accepted neurotransmitter, and that the INMT/AADC enzyme concentrations were highest in the visual/frontal cortex, pineal and choroid plexus, not necessarily throughout the brain. Nonetheless, other studies have shown INMT in the retina and spinal tissues, and DMT has been found in human CSF, making for the possibility that DMT is a somewhat ubiquitous CNS substance. I believe the original criticism was ill considered and that the 2019 Dean et al. study should have laid such misbegotten ideas to rest. However, I understand the criticism yet persists. The truth will come out.

JC:  It was quite strange that some critics would take a pharmacological perspective on how endogenous DMT must show elevation in the periphery at similar levels to exogenous administration in order to be identified as having an effect on perception. What are your thoughts on the subsequent studies that should take place following the Dean findings?

Dr. Barker: The 2019 study illustrates the need to more closely map the human brain for INMT/AADC and determine the interconnectedness of those areas against what is known about their function. Similarly, perfusion studies should probe other brain areas to detect and measure DMT. We may then administer other drugs or substances to determine what produces increase/decreases/no effect on DMT levels in these areas. I would be very interested in completing my original LSD study; administer a range of known hallucinogens to see if their activity is mediated through increases in DMT, stimulating release, blocking reuptake, etc. Examining drugs that can affect the activity of INMT and AADC could also be helpful as would genetic manipulation of the INMT enzyme. These basic science studies should also be coupled to administration studies, of which several are underway or planned as well as physiologic/mechanistic studies of changes in DMT levels occurring in various meditation practices, hypoxia, near-death etc. Imaging techniques should also accompany such studies. Given DMT’s other recently discovered properties in neuronal plasticity, protection against cell death and neurogenesis, administration studies to patients with Parkinson’s, the dementias (particularly Alzheimer’s), etc. should also begin immediately. Many administration studies are also planned to study DMT’s effectiveness in depression, PTSD as well as other mental disorders. As a perhaps “ancient” neurotransmitter, all of the modern techniques of neuroscience need to be applied to understand its potential in medicine as well as perception and consciousness.

JC: I agree that a deep dive is definitely in order and long overdue. Hopefully some of the organizations delving into the psychedelic “gold rush” are keen to explore the areas of endogenous DMT/5-MEO interplay with exogenous psychedelics. What are your thoughts on the 8 separate human EEG studies on DMT/5-MEO, Ayahuasca and Psilocybin all showcasing very similar oscillators changes such as alpha suppression and gamma increase? Is this enough data to reliably state that serotonergic psychedelics reliably induce an increase in gamma power?

Dr. Barker: Interpretation of EEG patterns is far outside my expertise. I imagine one would expect to see similar patterns for the hallucinogens you mention since they have many physiological and behavioral effects in common as well as neurochemical correlates.

JC: Circling back to your unpublished LSD study which showed an upregulation of endogenous 5-MEO by 1000% and endogenous DMT by 400%. I’ve been getting a massive amount of interest in this finding based on our citation of this in the first documentary. Do you believe that this effect is specific to serotonergic psychedelics or could non-serotonergic compounds such as ketamine or cannabis potentially exude effects by similar mechanisms?

Dr. Barker: The experimental results showing elevations of endogenous 5-MeO-DMT and DMT following administration of LSD to Sprague-Dawley rats was conducted in 1981 and was wholly preliminary; limited number of animals and LSD administered at one dose. I did not get to repeat the experiment due to lack of funding within our Neuroscience Program at UAB and my taking another position as the Assistant Director of the UAB Comprehensive Mass Spectrometry Center later in 1981. However, several of our grant submissions around this time included these data and the intriguing hypothesis of explaining the mode of action of hallucinogens but NIH and NIMH showed no interest in funding its further research. DMT research at that time was seemingly relegated to the dustbin of science. However, with the renewed interest in hallucinogens as therapeutics, I am hopeful that a fully-funded effort to re-examine this possibility will soon be undertaken and that I will also be somehow involved.

Just as with many other drugs and their mode of action on specific neuroreceptors and neuroreceptor systems for the “known” neurotransmitters, some serotonergic hallucinogens may exert their pharmacology by acting as agonists, agonist/antagonists, or antagonists at a “DMT receptor”. Indeed, that may well be what is now known as the 5-HT-2a receptor system. They may also act as transport or reuptake inhibitors or facilitators. To be hallucinogenic, they would be expected to elevate the concentrations of DMT and/or 5-MeO-DMT at the synapse or replace them at their binding sites by possessing greater affinity. Since DMT administrations, as well as many other known hallucinogens, seem to act on the serotonergic system and cause serotonin elevation, I would assume that this is also part of endogenous DMT’s normal function. However, no receptor is an island unto itself. The possible permutations and combinations to be found in receptor binding and function, connectivity and various seemingly divergent yet interconnected functions in the brain could in some manner involve DMT in many physiological and mental events. This may also be why a variety of non-serotonergic compounds exert effects, through indirect yet connected roles. Since our knowledge about how hallucinogens do what they do is still lacking, I suggest we examine the ones that have the most in common first and then go from there. I have no doubt we could learn much from the effort.
JC: Speaking of the 5-HT2A receptor system pertaining to serotonergic hallucinogens… what are your thoughts on the fact that ketanserin completely abolished all subjective effects of psilocybin for human volunteers but failed to produce the same effect for ayahuasca users? There have also been anecdotal reports that ketanserin produced no abolishment of smoked DMT effects.
Dr. Barker: Ketanserin is a somewhat “dirty” drug in the fact that it is a non-specific antagonist of 5-HT2 receptors. So multiple receptors may be being affected. There is also an issue with comparing two “pure” substances, psilocybin and DMT, with ayahuasca, which is a complicated mixture of pharmacologically active substances. Nonetheless, there remains the possibility that there is a unique “DMT” receptor that may be complexed with the receptors of the 5-HT2a, etc., receptors and that is not affected by ketanserin binding or blockade. If psilocybin acts by enhancing DMT release, for example, ketanserin’s pharmacology against the activity of psilocybin may be seen as proof that the mode of action of hallucinogens occurs via such a mechanism, enhancement of endogenous DMT levels. Well worth investigating. We also know that there are a number of substances that have high affinity for the 5-HT2a systems yet are not hallucinogens. So there is obviously much more to the story.

JC: While there has been much focus on endogenous DMT and to a lesser extent endogenous 5-MEO, what are your thoughts on the potential interplay with endogenous monoamine oxidase inhibitors? There seen to be quite a number of them including tribulin/isatin, neurocatin, pinoline, & harman/norharman.

Dr. Barker: The 2013 paper demonstrating the presence of DMT in rat brain perfusate also reported on what we didn’t find. We found no evidence for 5-MeO-DMT, pinoline (6-MeO-THBC) or the harmans. While we did see the MAO product of TA, NMT and DMT- indole-3-acetic acid, we did not see the corresponding metabolite for 5-MeO-DMT. The perfusate “covered” the pineal and visual cortex so these compounds may yet be confirmed somewhere else in the brain. Nonetheless, since MAO is the major metabolizing enzyme for DMT and 5-MeO-DMT there may well be some synergistic regulatory pathway that “protects” these compounds from clearance, allowing longer action, higher concentrations and a chance for reuptake and storage. There has yet to be any research of which I am aware that has looked at the activity of these substance in relation to DMT.

JC: While serotonin and melatonin are most well known as modulators of brain function and circadian rhythm, both compounds have been found extensively in the gut. A 2005 study found significant levels of butofenin in the stool of humans. Do you believe that DMT/5-MEO could possibly be found in the gastrointestinal tract at similar concentrations to melatonin and serotonin?

Dr. Barker: The 2005 Karkkainen et al. study did look for DMT and 5-MeO-DMT in human stool samples as well. DMT was observed in only one sample at exquisitley small levels and no 5-MeO-DMT was reported. Since unmetabolized bufotenin was found, it is highly probable that it arose from gut bacterial biosynthesis or from the epithelial cells lining the gut. Oral bufotenin, like DMT, undergoes significant first pass metabolism and is not orally active and would not survive the long march to the gut. Thus, it is possible that locally produced bufotenin, like serotonin and melatonin, does have a role to play in gut function or signaling. If DMT or 5-MeO-DMT were synthesized there, I would have expected them to survive as bufotenin did.

I guess my answer to your question is no.

JC: An organization has recently launched a research trial to observe whether sub-psychedelic levels of intravenously administered DMT can help human stroke patients recover from their neurological damage. What are your thoughts on utilizing DMT in a therapeutic, non-hallucinatory manner?

Dr. Barker: I am aware of the study in stroke patients and anxiously await their results. Although the emphasis in hallucinogen research has been the extraordinary states of consciousness they produce, there is now an explosion of interest in their therapeutic potential in a range of disorders, particularly of the CNS. Recent data have shown DMT (and ayahuasca) to protect neurons against hypoxia, stimulate neuro-neogenesis, enhance neuronal repair and enhance brain plasticity. Knowing that DMT is an endogenous neurotransmitter, it is possible that it plays a “normal” role that is, on a daily basis, somewhat detached from and far more subtle than the extremes of “overdosing” on DMT through exogenous administration. We have noted in the past the possibilities of its involvement in perception and consciousness, including creativity, imagination, dream states, etc. Thus, disorders of this putative DMT system, as occurs with other neurotransmitters, could explain or be involved in a range of such disorders; depression, autism, Parkinson’s, Alzheimer’s, etc. for which there have yet to be adequate neurochemical explanations. In the case of stroke patients, it is hoped that the observed effects of DMT in enhancing neuronal survival, neuronal repair, neuro-neogenesis and plasticity will help recovery in stroke-affected and related brain-damaged patients. While the hallucinatory effects of DMT are of great interest to understand, that cannot be its sole purpose as a neurotransmitter. Thus, administration of “supplemental” DMT, sub-hallucinogenic doses or infusions, may well inform us of its possible natural role and its potential as a therapeutic. It is a problem that DMT has to be injected/infused rather than being able to use a pill or some similar oral product. Perhaps insufflation or “vaping” could be used but we will eventually need a simple way to dose DMT to be able to observe longer term beneficial effects. No doubt, it will lead to the development of DMT analogs that are orally active and potentially even more efficacious. I am very enthusiastic about allowing science to pursue the therapeutic potential of the hallucinogens in general and DMT in particular. After decades of what can only be seen as government and cultural repression of such research, it is long overdue.

JC: It appears as though there is data indicating that DMT has anti-inflammatory and cellular protective functions as you mentioned. While some believe that endogenous DMT dysregulation is the cause of psychiatric disorders, there also appears to be data indicating that chronic neural inflammation is correlated with these disorders. Since DMT has anti-inflammatory and protective qualities, is it possible that instead of being the “cause” of these mental disorders that DMT is instead part of the autonomic repair process and “overshoots” of this repair process coincide with hallucinatory experiences?

Dr. Barker: Such a possibility may someday be examined but currently there are no data to either support or refute the hypothesis. More research is definitely necessary.

JC: It was recently announced that you joined the advisory board of Pharmadrug a company focused on the research and development of psychedelic compounds for therapeutic uses. Do you believe developing a more thorough understanding of endogenous DMT/5-MEO will be a part of the venture?

Dr. Barker: Yes

— End Interview

2021 is shaping up to be quite an exciting time for endogenous DMT research as it appears as though more funding is being generated for this under-supported field. We look forward to what Dr. Barker and his team generate in terms of data pertaining to DMT, 5-MEO, and much more.

E-mail me at with any comments or questions.

DMT Quest is a non-profit 501(c)3 dedicated to raising awareness and funds for endogenous DMT Research. This specific field of psychedelic research has been underfunded for many decades now. It’s time to take our understanding of human physiology, abilities, and perception to the next level. You can follow us at Facebook, Instagram, or Twitter.