While there hasn’t been any new, direct endogenous DMT research published since the 2019 study authored by Dr. Jon Dean, there has been some fairly intriguing periphery research that has taken place in recent times. A 2021 in vitro and in vivo animal study published in the journal Frontiers in Immunology found that hypoxia drives tryptophan metabolism towards enhanced tryptamine production. With tryptophan being the key building block of both serotonin & DMT, and with tryptamine being the direct precursor to DMT synthesis, it appears as though this provides yet additional periphery evidence of one of the potential mechanisms for modulating the production of endogenous DMT. The significance of this research is that the upregulation in tryptamine synthesis appears systemic being that it was measured in the brain, blood, and liver.
Hypoxia is a condition in which the body or a region of the body is deprived of oxygen at the tissue level. The authors of the 2021 study hypothesize that high altitude-induced hypoxia induces the upregulation of endogenous tryptamine synthesis (DMT) leading to the subsequent hallucinatory experiences. Another method to induce hypoxia is via hyperventilation that can induce vasoconstriction limiting the amount of blood flow to the brain. For those still wondering whether a person can in fact modulate their own neurochemistry and DMT via targeted breathing techniques, the evidence continues to pile up. A 1994 study published in The Annals of Neurology utilized hyperventilation to induce hypoxia followed by orthostasis (lowering blood pressure) and a Valsalva maneuver (full expiration w/nose pinch) to induce hallucinations (visual or auditory) for 60% of the subjects. Obviously cerebral hypoxia takes place during many reported near death experiences (NDE’s) fitting in quite nicely with the endogenous DMT discussion revolving around NDE’s.
Another intriguing study that took place in 2021 was published in the journal Scientific Reports observing the gene expression changes in the human brain following death. The researchers would remove human brain tissue during routine surgery and measure the gene expression changes for all genes from 0 to 24 hours. It was observed that about 80% of the genes remained stable in the 24 hours following tissue removal while neuronal gene expression linked to memory and thinking degraded rapidly in the hours following tissue removal. At the same time that degeneration of neuronal gene expression took place, upregulation of gene expression took place in the astrocytes and microglial cells that would peak at 12 hours. This is intriguing in light of the finding that the brain doesn’t simply linearly degrade following death.
In the past I’ve speculated that astrocytes were a likely candidate as a potential source for DMT synthesis in the brain with the belief that they contained the gene indolethylamine-n-methyltransferase (INMT) necessary for DMT formation. An interesting facet is that while neuronal activity is considered to be the foundational signal being acquired during fMRI brain imaging, a 2018 study indicates that astrocyte activation can also induce similar signaling without neuronal activity. This indicates that the brain can potentially continue a variant of signaling mechanisms without neuron based activity and in the case of a dying brain… the upregulation of genes in the astrocytes and microglial could indicate that some sort of processing is still taking place many minutes and hours after death. This doesn’t necessarily indicate that a person’s consciousness stays within the brain for hours following the moment of death but it does cause one to question whether a person can maintain some level of consciousness in the brain without the classic neuronal firing. Hopefully in the future, a follow up study can take place that is able to measure for INMT gene expression in the minutes and hours following brain tissue death.
While I’ve cited the 2005 research outlining the significant presence of bufotenin (5-HO-DMT) in the stool of humans in the past, more recent research has taken place indicating that endogenous DMT is synthesized in the intestinal tract of mammals. A 2019 animal study published in the journal ACS Chemical Biology presented the development of nuclear magnetic resonance technology to measure tryptophan metabolism ex vivo. The researchers found that they were capable of measuring various metabolic pathways of tryptophan utilizing this method and observed the presence of DMT in the stool. Based on the information reviewed thus far, it appears as though DMT is produced in several parts of the mammalian brain (cortex, choroid plexus, pineal gland) as well as in the large intestines. There lies the potentiality that much like serotonin and melatonin, that the majority of endogenous DMT is produced in the gut and provides very fundamental functions regarding gut barrier integrity. As we continue to learn about the relationship between the gut, brain and our emotions/perception, the role of DMT within our digestive tract could be an important factor going forward.
In recent times, there has been a replication study of sorts that has taken place regarding the effects of sub-psychedelic doses of DMT on in-vitro neuronal growth. It was announced by Algernon Pharmaceuticals that sub-psychedelic levels of DMT administered to neurons in-vitro induced a 40% increase in cortical neuron growth. In 2018, a study in the journal Cell Reports also reported neuronal growth following in-vitro administration of DMT to neurons. The significance of this recent pre-clinical study is that the amount of DMT administered varied between 100 picomolar and 30 nanomolar levels. These levels appear to fall within the range of DMT observed in the 2019 endogenous DMT study. Perhaps in the future we will be able to monitor in real-time techniques that can upregulate endogenous DMT and induce similar positive effects on the brain.
While this 2021 hypothesis paper in Frontiers in Human Neuroscience isn’t directly correlated with DMT, it seems intriguing nonetheless based on it’s implications regarding the conscious experience and gamma oscillations. The author, Dr. Joachim Keppler attempts to present the potential development of a comprehensive theory of consciousness (TOC) which includes the zero-point field (ZPF) acting as the underlying source of the electromagnetic field. The theory also ties in the brain’s oscillatory pattern’s and neurotransmitter balance that signify variations of coupling with the ZPF. Keppler has also written an intriguing hypothesis paper regarding the fundamental mechanisms of hypnoanalgesia as it pertains to the ZPF. Being that exogenous DMT (in various forms) seems to reliably increase gamma oscillatory power and that gamma power is also increased during many variations of altered states, it would seem that an integration of endogenous DMT inquiry (and/or Endohuasca) would make sense to develop a truly comprehensive framework of consciousness.
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