Attention: All hyperlinks in this piece are to the full peer-reviewed studies being referred to. Just click on them to access the references.
A new study published in Scientific Reports definitively observed that indolethylamine-N-methyltransferase (INMT) is found in both human and rat brains throughout the cerebral cortex, choroid plexus, and pineal gland. The importance of this finding is based on the fact that INMT is the enzyme responsible for biosynthesizing DMT from tryptamine. Prior studies were inconclusive regarding this based on out-dated protocols that lacked sensitivity.
The researchers found that in vivo extracellular levels of DMT in the cerebral cortex of normal behaving rats with or without the pineal gland were similar to those of serotonin. One of the most interesting (yet not surprising) findings of the study was that DMT levels increased significantly in the visual cortex of rats following induction of cardiac arrest. These increased levels of DMT in the visual cortex were independent of an intact pineal gland.
It appears clear to us that this is likely the most significant study of 2019. This is based on the fact that it redirects the conversation of a pineal-centric conversation regarding DMT to a brain-centric one. This within itself is a much more functional and realistic perspective regarding the distribution of endogenous DMT and localized synthesis/activation. The speed of action is key and a glandular secretory-blood distribution model seemed intuitively unrealistic. While some folks still cite Dave Nichols’ pharmacological perspective as a reason that DMT is likely not associated with visionary experiences, this new study essentially makes his argument obsolete. The other key finding was the likelihood that the colocalization of INMT and Aromatic L-amino acid decarboxylase (AADC) found in the brain is necessary to synthesizing DMT. The neurological colocalization of these 2 enzymes seems to differ from the peripheral nervous system INMT (with scarce AADC) which largely contributed to the proposed lung-centric-blood distribution model.
This recent study was undertaken by some of the same researchers (Dr. Jimo Borjigin , Dr. Michael M. Wang, Dr. Tiecheng Liu, Dr. Sean Huff) that undertook the 2013 study in the Proceedings of the National Academy of Sciences which observed global and highly coherent surges of gamma waves in the brain following cardiac arrest in rats.
(Image from the 2013 cardiac arrest study. Red bar indicates cardiac arrest activity and the brain wave bands are listed bellow from left to right – delta, theta, alpha, beta, low-gamma, medium-gamma, high gamma, ultra gamma (165-250 Hz))
These two studies appear to provide additional evidence that endogenous DMT (amongst other biochemicals) is distinctly correlated with gamma wave activity and likely the visionary states associated with near-death experiences. Periphery evidence regarding the surge in gamma waves from Ayahuasca and exogenous DMT have been cited incessantly here at DMT Quest over the past years. We’ve also touched upon the findings that lucidity in dreams (both externally induced & naturally occurring), meditation, and even mystical experiences induced by low frequency magnetic fields (“The God Helmet”) are distinctly correlated with enhanced low gamma frequency (40 Hz). In addition, multiple studies have found that increases in gamma oscillations are intimately intertwined with visual stimulus within the visual cortex (1, 2, 3, 4, 5, 6, 7, 8). While it is still unclear as to exactly what cells in the brain are responsible for the DMT measured in extracellular fluid, we believe that astrocytes provide a reasonable starting point. A 2014 mouse study published in the Proceedings of the National Academy of Sciences found that astrocytes are necessary to maintain functional gamma oscillations both in vitro and in awake-behaving animals. Another 2018 study in the Proceedings of the National Academy of Sciences observed that astrocytes regulate the transmission speed of neurons by changing the myelin structure.
Another intriguing finding within the recent DMT study was that normal waking rats exuded extracellular DMT levels in the brain similar to the levels of serotonin. It was also noted that basal concentrations of DMT were within the same range as the basal concentrations of serotonin, norepinephrine, and dopamine. This alludes to the notion that DMT plays a key role in normal waking perceptual states much like the other neurotransmitters in the brain/body. Is it possible that human brains are synthesizing and recycling DMT from every waking breath?
A 2017 study in the journal Frontiers of Neural Circuits found that gamma oscillatory strength was phased locked to breathing. This seems indicative that certain levels of endogenous DMT in balance with multiple other neurotransmitters provide the biochemical mix for “regular” perception and that respiration indirectly modulates these levels. A 2010 study published in Science observed that astrocytes control breathing by sensing changes in brain pCO2/pH and release ATP to induce adaptive increases in breathing. A 2018 study published in Nature Communications found that astrocytes modulate activity of the central nervous system generating the respiratory rhythm while contributing to adaptive respiratory responses in conditions of increased metabolic demand.
(26 Guinness World Record Holder… Wim Hof)
Now that it’s been verified that endogenous DMT brain levels are similar to other common neurotransmitters, it begs the question of the more subtle aspects of this biochemical. For instance, in Dr. Rick Strassman’s exogenous DMT study, sub-psychedelic (non hallucinatory) doses of DMT produced the effects of “smiling and/or laughing” in the volunteers. A recent 2019 study published in ACS Chemical Neuroscience observed that the chronic administration (every 3rd day for 2 months) of microdoses of DMT (10% of psychedelic dose) administered to rats provided relief from depression and anxiety. This implies that DMT not only plays a key factor in our visual perception but also our emotional stability and mood regulation.
(For whatever reason it seems as though some people believe this study proves that the pineal gland has no influence in terms of the brain levels of DMT or influence on the NDE experience. We believe that this is an emotional misinterpretation of the results of the study. The results provide conclusive evidence that the pineal gland of humans produces DMT based on the enzymatic composition of the gland. The levels of DMT in the extracellular fluid in the cerebral cortex (outer layer of the brain) of rats following cardiac arrest averaged 2.84 ± 1.65 (w/pineal gland) vs. 1.84 ± 0.89 (without pineal gland). Due to the small sample size and possibly the subtle variabilities of anatomical location of the sampling per animal it’s difficult to extrapolate too much from these statistics. However, the researchers cite that no significant difference was measured which is not equivalent to stating that there was no difference. There was a difference but not to the extent that the pineal gland is responsible for the majority of extracellular cerebral cortex DMT. We would presume that based on the anatomical location of the pineal gland (mid-brain) that it would likely be more influential on the extracellular DMT levels in the third ventricle, thalamus, & hypothalamus. In terms of the effects (or lack thereof) of pinealectomy on the experiential aspects of the NDE experience, that is an extremely difficult aspect to quantify using animal studies. We just find it strange that there is an interpretation of this study as putting the “pineal theory to rest” as we do not interpret the results as such. The study indicates that multiple areas of the brain… pineal, choroid plexus, and cerebral cortex likely synthesize DMT and utilize them locally within their respective regions.)
So now what?
Where does the research progress to?
We would assume that future studies identifying the cellular origin of DMT throughout the brain is in order. We propose that a reasonable starting point would be astrocytes located throughout the cerebral cortex and ependymocytes located at the choroid plexus. A 2018 study published in the Journal of Pineal Research observed that the choroid plexus (origin of cerebrospinal fluid (CSF) production) produces melatonin. While past studies hypothesized that CSF levels of melatonin had a pineal origin, this new finding indicates that the choroid plexus could serve as the predominant secretory organ. In regards to DMT, the CSF has been observed to contain the highest concentrations when compared to blood, urine, and saliva. There lies the possibility that much like melatonin, the origin of CSF-DMT is the choroid plexus and that the CSF acts as a distribution medium for DMT much like it does for serotonin and other neurotransmitters.
An additional study that must take place is a repeat of the recent study which attempts to measure changes in extracellular DMT levels immediately prior, during, and promptly following cardiac arrest. It appears as though the recently published study did not focus on this aspect. This would further develop the model of the biochemical changes taking place that induce the timely global surge of gamma oscillations following cardiac arrest.
We will list a few studies which we feel could add further important insights into the physical correlates of the experiential near-death experience from cardiac arrest (as well as a few others).
Perform the same study while measuring extracellular levels of endogenous monoamine oxidase inhibitors (MAOIs) Isatin/Tribulin , Neurocatin, Pinoline, & Tryptoline. This would give insights into whether the mechanisms of increased DMT following cardiac arrest are predominantly based on increased synthesis of DMT, decreases in metabolization via upregulation of endogenous MAOI levels, or a combination of both. In essence, a deeper probe of the Endohuasca system.
Perform additional analysis of INMT/AADC/DMT(s) located in the enteric nervous system within the gastrointestinal tract. We hypothesize that DMT(s) are synthesized systemically throughout the body much like melatonin and serotonin.
Perform EEG analysis and extracellular brain DMT levels during cardiac arrest of INMT-KO animals to verify whether any changes in the gamma frequencies take place from the lack of DMT. A 2015 study published in the Proceedings of the National Academy of Sciences observed significant surges of the levels of the neurotransmitters serotonin, adenosine, dopamine, norepinephrine, GABA, glutamate, acetylcholine, taurine, histamine, glycine, and aspartate following asphyxia induced cardiac arrest. There will be difficulties parsing out what specific matrix of biochemicals correlate with different frequency oscillations but it should be investigated nonetheless.
Inject mice with various doses of DMT while measuring the extracellular cerebral concentrations of the 11 neurotransmitters associated with the asphyxia induced cardiac arrest. This would give more comprehensive insights as to the synchronous biochemical cascade effects within the brain from exogenous DMT. In Dr. Rick Strassman’s exogenous DMT human study he observed a dose dependent increase in blood concentrations of β-Endorphin, cortisol, corticotropin, and prolactin levels (growth hormone rose equally to all doses). There lies the potentiality that the amount of DMT involved in modulating the NDE experience is much less than the amount needed to induce a mystical experience exogenously due to the naturally supportive roles of multiple neurotransmitters acting in synergy. When ingested exogenously, DMT acts as a catalyst that induces upregulation of multiple other biochemicals in addition to directly stimulating multiple receptors directly. We must remember that no chemical acts singularly so when people claim that DMT is or isn’t a factor in the NDE experience they are missing the big picture. DMT is but one of multiple chemicals playing a role in the experience and this is not too different than the exogenous DMT experience as well.
Perform the same cardiac arrest study while measuring for any changes in blood plasma levels of all neurotransmitters in order to better comprehend the ratio of extracellular brain surges compared to circulating blood levels in the periphery.
Utilize induced hyperventilation techniques in rats while measuring extracellular DMT brain levels pre-, during, and post hyperventilation. This study would provide evidence for increased DMT synthesis in humans when utilizing techniques such as the Wim Hof Method, Holotropic Breathing, Pranayama, etc. A 2002 study in the journal Neuroimage observed that hyperventilation evoked enhanced gamma activity.
A circadian rhythm study is in order to better understand the potential changes in circulating DMT(s) as well as MAOIs. 24-hour measurements of cerebral cortex extracellular fluid levels of these compounds is needed. Based on the gamma oscillatory surges during REM sleep & the tight correlations between lucidity in dreams & the 40 Hz bandwidth, we would not be surprised to observe a significant change in the levels of these circulating compounds during dreams. (Add on: A similar study involving prolonged exposure to complete darkness (3 to 10 days) would offer physiological insights into the visionary experiences during the esoteric practice of Dark Room Retreats.)
Replicate the unpublished study Dr. Steven Barker mentions in an interview in which rats administered LSD saw a 1000% increase in 5-MEO-DMT and a 400% increase in DMT. He made no mention of the anatomical location of measurement of these increases. Dr. Barker stated that there lies the possibility that there is an “endogenous hallucinogen neuronal system” and that many hallucinogens might not be true hallucinogens but rather agonists of this system.
A peripheral nervous system investigation of DMT synthesis seems important. While the focus of the DMT discussion is largely based on the visual effects of the chemical based on altered brain activity, our perspective is that enough evidence has been produced to explore it’s role in the periphery. DMT has been observed to exude anti-inflammatory effects via the Sigma-1 receptor throughout the central nervous system and the peripheral nervous system. Exploring the potential of mast cell synthesis of DMT might offer some insights being that mast cells synthesize serotonin and melatonin in the periphery. Our speculative unfounded and likely ungrounded opinion is that DMT represents an increase of oscillatory speed inducing subsequent effects. Increased oscillatory speed in the brain induces perceptual changes while increased oscillations in the periphery might correlate with accelerated wound healing , regeneration, and potentially increased magnetic field strengths observed during “spiritual” practices. We speculate that DMT is not only intimately intertwined with strange perceptual alterations but likely also strange abilities as well.
Exposing rats to different magnetic fields of varying strengths/types and measuring the cerebral extracellular levels of DMT(s) and MAOI. Dr. Michael Persinger (RIP) had a hypothesis in 2003 that the mystical effects of the “God Helmet” device (which induces increase in gamma oscillations) were based upon upregulation of DMT in the brain.
A futuristic study would incorporate attempting to measure biophotonic emanations from the head/brain following intravenous DMT administration to rats and humans in a dark room setting. There lies the possibility that DMT could induce the emanation of biophotons at a specific wavelength differentiating it from other neurotransmitters. If this is possible then the cardiac arrest study can be replicated to measure the biophotonic emanation from the brain of rats during the process. This could then be translated in non-traumatic human studies that attempt to measure DMT fluctuations during breathing exercises (WHM, Holotropic, etc.), meditation, hypnosis, dream states, and Out-of-Body Experiences. A 2005 study published in the Journal of Psychoactive drugs observed that DMT in the leaves of the Psychotria Viridis tree exuded the greatest amount of absorbance for the UV spectrum between 280 nm to 315 nm. It’s plausible that endogenously produced DMT emanates biophotons within this same UV bandwidth. If a protocol like this could be developed then it’s plausible that non-invasive methodology could be utilized to measure endogenously produced DMT in the future. (Add on: It’s possible that we are mistaken but a technology called “proton magnetic resonance spectroscopy” has the ability to provide a quantitative noninvasive assessment of regional brain biochemistry. Being that this technology has been used to measure brain levels of neurotransmitters GABA, glutamate, and glutathione… we speculate that it can be used to non-invasively measure endogenous DMT(s).)
*A 2019 study published in Nature Physics showcased the ability for scientists to utilize scanning tunnelling microscopes as an MRI device to measure the magnetic fields of specific atoms. The scientists found that they were able to distinguish different kinds of atoms based on their magnetic field signature even when the atoms were next to each other. The researchers believe that this same technology can be utilized to mapping out the magnetic and spin properties of entire molecules in the future.
We believe the endogenous DMT/Endohuasca field of study to clearly be the most important in the world today pertaining to biology. It’s a damn shame that more funding isn’t widely available for this field of research regarding the enodgenous “hallucinatory” system. At a minimum, this field deserves the same amount of funding as genetic research ($3 billion annually) especially considering the ramifications. The fact that it’s now established that normal waking rats secrete levels of DMT comparable to serotonin provides some support to the notion that “reality” is “hallucinatory” by nature. It would be no surprise to observe the same mechanisms in all homo sapiens. The human understanding of perception, perception alterations, and strange abilities seems to lie somewhere in the realm of this particular field. The fact that this research is providing a definitive chemical correlation to unfathomable experiences such as NDE’s is important to progress our understanding of the human experience. The measurement of gamma wave surges during these experiences indicates that the processing speed of experience accelerates during these moments. The brain seems to essentially discard the slower oscillations that assist in processing the “3-D reality” and instead the percentage of oscillations is dominated by speed aka gamma waves.
PS. For those still claiming that there is no proof that the human brain produces and utilizes DMT in the name of “rigorous scientific thought process”… we envy your anal rigidity. It’s now clear that the enzymes necessary for endogenous DMT production (colocalized INMT/AADC) are found in the human brain and the rat brain. It’s also clear that humans possess and utilize the same vast array of neurotransmitters that rats employ (serotonin, melatonin, adenosine, dopamine, norepinephrine, GABA, glutamate, acetylcholine, taurine, histamine, glycine, aspartate). Why it would be so surprising that humans produce yet another neurotransmitter that rats do such as DMT in conjunction with the others is beyond us. It’s simply another chemical being synthesized by the human body that induces effects on our perception much like our smaller mammalian counterparts. Unfortunately we are relegated to rat studies regarding in vivo experiments being that there is an issue with efficacy of measuring brain fluid in waking adult humans. Perhaps some of you taking the “hard stance” would like to submit yourselves to having long needles stuck in your brain to definitively verify whether DMT is found in normal waking humans… in the name of “rigorous scientific analysis”. These poor rats… sacrificing their lives by the hundreds of thousands in laboratory experiments only to be discarded as “rat studies” that do not translate to anything other than “rat studies”. We believe that many people employ pseudo-scientific thought processes that are not based on reasonable, well informed research. Unfortunately it has become very popular to feign the stance of “hard science” while being ignorant of the dozens of intricate details that all point to human brains synthesizing and utilizing DMT alongside many other endogenously produced biochemicals. In many cases these are the same people that cite the “Big Bang” theory as being immaculately scientifically supported all the while willfully ignoring all the data supporting the production of a measly neurotransmitter in their own brains. AMAZING!
(Any volunteers in the name of “rigorous scientific inquiry”?)
E-mail me at email@example.com 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 also follow us at Facebook, Instagram, or Twitter.