On June 27, 2019, University of Michigan PhD candidate Jon Dean published a study titled, “Biosynthesis and Extracellular Concentrations of N,N-dimethyltryptamine (DMT) in Mammalian Brain“. It received significant media coverage amongst outlets dedicated to all things psychedelic. The research results within the paper seemed important in light of all the speculative discussion that’s taken place since the 2013 animal study that found DMT and it’s precursors within the pineal gland of live rats.
One of the more vocal voices regarding the criticism of endogenous DMT and it’s implications regarding physiology is pharmacologist Dave Nichols. In 2017, Nichols would present a talk titled, “DMT and the Pineal Gland: Facts vs. Fantasy” at Breaking Convention in the UK. In this presentation he would present his perspective on why he believed the pineal gland was incapable of producing DMT at the necessary levels to contribute to mystical experiences. I offered a rebuttal in a piece titled, “Dave Nichols is Correct about DMT and the Pineal Gland… Partially“. The following year, Nichols would pen a review in the Journal of Psychopharmacology titled, “N,N-dimethyltryptamine and the pineal gland: Separating fact from myth“. One of the main points in his write-up is his belief that DMT is not produced at significant concentrations and that there is no evidence for DMT’s accumulation within the brain.
One of the most significant new pieces of data presented in Dean’s 2019 paper is that one of the key enzymes responsible for the biosynthesis of DMT, Indolethylamine-N-methyltransferase (INMT) was unequivocally found throughout the different parts of the rat and human brain (pineal gland, cerebral cortex, choroid plexus). Up until this time Dave Nichols had openly stated that DMT was found in “huge” quantities in the lungs (based on the identification of INMT concentrations in lung tissue). He can been seen making this statement in the video below.
This piece will offer commentary of Nichols’ most recent critique which was published on November 15, 2019 titled, “DMT in the Mammalian Brain: A Critical Appraisal“. We will start our review of the second paragraph of the critique.
Nichols: The recent publication by Dean et al. (2019) is the next iteration in attempts by the some of the coauthors of this publication to prove that endogenously produced DMT has important physiological functions, and in particular could be responsible for the mental effects of a near death experience. In this publication, they report that DMT is found in rat brain visual cortex, with slightly elevated levels of DMT in brains of rats that were asphyxiated. Previously, some of these authors had proposed that DMT is produced in significant amounts by the pineal gland (Barker, Borjigin et al. 2013). One of us has reviewed that hypothesis and has pointed out that the pineal gland is not capable of producing physiologically relevant amounts of DMT (Nichols 2018). The present report by Dean et al. showing that DMT could be detected in rat brain in similar amounts, regardless of whether or not the animal had a functioning pineal gland, is consistent with our earlier argument.
JC: It’s interesting wording to begin with that some of the coauthors are looking to prove that endogenously DMT has “important” physiological functions. From what I understand, there is no known biochemical in the body that has definitively been proven to have no function. Therefore research regarding DMT or any biochemical for that matter is based on identifying it’s function. Whether it’s considered “important” is based on the perspective of the perceiver. DMT levels in the visual cortex of asphyxiated rats increased 600% within one hour following cardiac arrest. Whether this is considered as “slightly elevated” or “significantly elevated” is up to the perceiver. I do find it strange that Nichols makes no mention of the new finding that the same machinery utilized to synthesize DMT in the pineal gland is now found at the choroid plexus and throughout the cerebral cortex. The choroid plexus discovery is especially interesting being that it is the predominant site for cerebrospinal fluid production (CSF) and is also known to contribute to melatonin synthesis. A 2010 review in the journal Cerebrospinal Fluid Research observed that alongside the waste removal and nutrient based tasks of the CSF, it also acts as a distribution medium for neuroactive substances.
Nichols: In a previous publication by some of these coauthors (and prior to their studies focusing on DMT), Li et al. (2015) emphasized that asphyxia generates a “brainstorm” of neurochemicals. To wit, “An immediate and sustained surge of a large set of core neurotransmitters within the cortex occurs in response to asphyxia. In both frontal and occipital cortices, a dramatic and significant surge of neurotransmitter secretion was detected for as long as 20 min of asphyxia for all neurotransmitters tested.” They found that cortical levels of serotonin (5-HT) surged more than 20-fold, norepinephrine more than 30-fold, and dopamine more than 12-fold. Additionally, levels of glutamate and other neurotransmitters including acetylcholine, adenosine, aspartate, taurine, histamine, and glycine all surged within minutes after asphyxiation. Thus, it is curious that Dean et al. (2019) focuses only on DMT as an important player in brain death within this context.
JC: He’s reiterating information generated by Jimo Borjigin’s lab, the same lab in which Dean performed this most recent study. It seems evident that since there is no clear, definitive physiological function for endogenous DMT that a researcher such as Dean would investigate this field. Since the data already exists that a “brainstorm” occurs following asphyxia that didn’t measure for DMT, it would make sense that a researcher would verify whether DMT is also a part of this “brainstorm”.
Nichols: Activation of brain serotonergic 5-HT2A receptors is the mechanism whereby hallucinogenic drugs such as DMT induce visual hallucinations and mystical experiences in humans (Nichols 2016). One of the metabolic pathways for the endogenous ligand of this receptor, serotonin, is N-methylation, catalyzed by the enzyme Indoleamine N-methyltransferase (INMT), for which serotonin was its first identified substrate. Previous work by Schmid and Bohn (2010) showed that high concentrations of serotonin can induce the mouse head twitch response, an animal proxy for hallucinogenic activity, via activation of 5-HT2A receptors. Thus, the surge of serotonin alone following asphyxiation could be responsible for activation of 5-HT2A receptors and production of (the behavioral metric used in laboratory animal studies of) psychoactive effects. In addition, if INMT is responsible for production of DMT, and INMT also N-methylates serotonin (Axelrod 1962), there should be a peak in the HPLC trace for N-methylserotonin, but that is not evident in the presented HPLC traces (and these two molecules do not co-elute in HPLC analysis). Further, N-methylserotonin also activates 5-HT2A receptors to produce behavioral effects (Schmid and Bohn 2010) and this metabolite would be expected also to contribute to potential CNS effects mediated by the 5-HT2A receptor following asphyxiation. It should be mentioned that INMT is not specific for N-methylation of tryptamine, but also N-methylates a variety of other arylethylamines including, tyramine, normetanephrine, metanephrine, 3-methoxytyramine, dopamine, and octopamine (Axelrod 1962), as well as histamine (Herman, Bowsher et al. 1985). Importantly, therefore, INMT cannot be seen strictly as a proxy for DMT production.
JC: Activation of the 5-HT2A receptors seems to be the mechanism with which psilocybin and LSD induce their visual hallucinations and mystical experiences. This is based on a combination of 5-HT2A receptor affinity and the utilization of Ketanserin (a 5-HT2A antagonist) pre-treatment to block the effects of psilocybin and LSD. Interestingly enough, a 2016 Ketanserin-Ayahuasca study failed to suppress the effects with the same magnitude as it did psilocybin and LSD. This alludes to the possibility that either DMT mediates it’s effects via receptors other than 5-HT2A and/or the monoamine oxidase inhibitors (MAOI’s) in Ayahuasca disrupt the effects of Kentanserin. One interesting statement made by psychedelic researcher Hamilton Morris is that some subjects have claimed to have taken 30 mg of Ketanserin prior to smoking DMT with no changes in the effect. It’s a bit perplexing why Nichols would claim that DMT exudes its mechanisms via activation of the 5-HT2A receptor when there has yet to be any official Ketanserin-DMT studies to date. Nichols would go on to site the effects of high levels of serotonin inducing a head twitch response in mice which is a proxy for hallucinogenic activity. This is a bit perplexing in light of there being no evidence of high levels of 5-HTP (a serotonin precursor) administration in humans as inducing any sort of hallucinatory phenomena. 5-HTP easily crosses the blood brain barrier and increases central nervous system synthesis of serotonin. A study involving monkeys raised the levels of their brain serotonin 200-fold following intravenous 5-HTP administration at 20 mg/kg. If Nichols is claiming that serotonin is a hallucinogen (first that I’ve ever heard of) at high levels within the brain then he should provide evidence based on human studies since these would be easily executed. Being that the LD50 of oral 5-HTP in rats is 243 mg/kg, there is enough room to induce significant surges in cortical serotonin levels without fear of lethality. In the same vein of speculation, there also lies the potentiality that huge surges in serotonin induce or coincide with an upregulation of endogenous DMT which causes the head twitch in mice. The following statement is confusing… “In addition, if INMT is responsible for production of DMT”. This is strange in light of Nichols clearly stating that DMT is found at huge levels within the lungs (based on INMT concentrations) but is now seemingly retracting this stance to throw doubt on whether INMT plays a role in DMT production. It’s as if he was sure that INMT contributed to lung DMT but now that INMT is found throughout the brain, there is reason to doubt the INMT hypothesis. The fact that INMT is not specifically relegated to DMT synthesis is not exactly a secret being that Dean himself sites this in his recent paper, “Peripheral INMT may be responsible for established DMT-independent functions such as methylation of sulfur-containing compounds, histamine, and selenium metabolism”. Dean also states that to unequivocally demonstrate that INMT is responsible for the production of endogenous DMT that INMT-deficient animals need to be studied.
Nichols: As for the other neurotransmitters found to be dramatically induced in the cortex by asphyxia in the author’s earlier work (Li, Mabrouk et al. 2015), norepinephrine has a central effect on arousal and alertness and also activates adrenergic receptors that are co-expressed on apical dendrites of cortical pyramidal cells, the same anatomic location where 5-HT2A receptors are expressed. Dopamine plays important roles in arousal, attention, cognition, and affective emotion. Increased brain glutamate concentrations can lead to out of body and hallucinogenic experiences (Gouzoulis-Mayfrank, Heekeren et al. 2005, Browne and Lucki 2013), and is a mechanism involved in the out of body experience induced by the anesthetic ketamine. With such a flood of neurochemicals, including those that can significantly impact CNS function and induce out of body experiences, it is not clear why the authors attach such importance to the relatively small increase in the amount of DMT in the brain following asphyxiation. Apparently, it is the recurring meme that because exogenous DMT is hallucinogenic, and because it can be produced in the brain, therefore it must be important there, and have some physiological (hallucinogenic?) role.
JC: Nichols essentially reiterates his previously discussed points (2017, 2018) that increases in other neurotransmitters modulate the experiences following asphyxia based cardiac arrest. This is nothing profound being that it’s clear that no experience is a singular occurrence neurologically. Even exogenous psychedelic ingestion is not singular being that the ingestion of LSD causes an increase of glutamate (as cited by Nichols himself), an increase in serotonin, a decrease in norepinephrine, and a fluctuation in dopamine. To go even further, an unpublished study cited by Dr. Steven Barker claims that LSD administered to rats induced a 400% increase in DMT and a 1000% increase in 5-MEO-DMT. Are we to begin questioning whether LSD itself has any significant physiological function based on the wide ranging effects of the substance on multiple endogenous biochemical levels? Nichols would reiterate the notion that increased glutamate levels in the brain can lead to out of body experiences. We already responded to this the first time being that this doesn’t preclude endogenous DMT from being involved based on the fact that glutamate exudes a linear relationship with hydroxyl radical formation which significantly suppresses monoamine oxidase (MAO) activity affording the possible upsurge of DMT, 5-MEO-DMT, Bufotenine, and other common monoamine neurotransmitters. Nichols then attempts to question why a researcher (Dean) who is interested in the physiological functions of DMT would study the machinery and fluctuations of DMT following asphyxia. It seems like Nichols is attempting to create a form of dissidence by questioning the thought process of anyone that believes that a hallucinatory compound such as DMT which is found throughout the mammalian brain might be related to naturally occurring hallucinations. This is all in light of a 2010 study showing that schizophrenics excrete bufotenine (5-HO-DMT) in their urine at levels 300% greater than normal volunteers. Why the whole notion of endogenous DMT, 5-MEO-DMT, or bufotenin being related to hallucinatory phenomena being a far-fetched notion to Nichols is a bit beyond me. It doesn’t appear that Dean or Borjigin have ever claimed that DMT is the singular biochemical reason for any occurrence being that they seem aware that the neural complexity of experiences is quite vast.
Nichols: Another explanation for out of body experiences, e.g. at near death, that the authors again fail to consider could be the production of dynorphin (DYN) and other endogenous opioid peptides. DYN and its cognate kappa-opioid receptor (KOR) play an important role in regulating stress responsiveness, motivation, and emotion (Bruchas, Land et al. 2010, Knoll and Carlezon 2010, Van’t Veer and Carlezon 2013, Donahue, Landino et al. 2015). DYN 1-13 is an extremely potent kappa receptor agonist, with 0.44 nM affinity at the kappa receptor in rhesus monkey brain (Emmerson, Liu et al. 1994). Readers will appreciate that salvinorin A, the hallucinogenic component of Salvia divinorum, is a selective and extremely potent agonist at the KOR that can produce hallucinogenic and out of body experiences (Roth, Baner et al. 2002). Other endogenous opioid peptides are produced during stress and would activate other classes of opioid receptors. The authors made no attempt in their work to measure production of endorphins.
JC: In the prior paragraph Nichols doesn’t know why Dean would focus on a singular molecule (DMT) related to the visionary experiences following cardiac arrest. Now Nichols attempts to interject a singular molecule as a potential explanation for the phenomena in the form of dynorphin. There seems to be a recurring theme of a lack of consistency amongst Nichols arguments. Sure dynorphin and other endogenous opioid peptides could play a modulatory role in the near death experience but that hardly precludes DMT, 5-MEO-DMT, Bufotenine, and endogenous monoamine oxidase inhibitors (MAOIs) tribulin, neurocatin, pinoline, harmane, or tryptoline from also playing modulatory roles. I find that the interjection of Salvia Divinorum as an exogenous hallucinogenic in support of the dynorphin hypothesis is quite hypocritical. The DMT argument is even stronger in this regard being that it is molecularly an apples to apples comparison of exogenous DMT and endogenous DMT. Nichols attempts to paint the picture of dynorphin essentially being a Salvia equivalent which has never been proven nor is there any clinical data to suggest that dynorphin induces the same or even a similar experience. A 1998 study published in the journal Clinical Pharmacology & Therapeutics showcased the effects of intravenously administered dynorphin to human subjects at the dose range of 0.25 & 1mg/kg. In the low dose range (0.25mg/kg), 50% of the subjects reported the side effect of a flushed feeling that subsided within 5 minutes. In the high dose range (1mg/kg), subjects reported a flushed feeling with burning and tingling sensations in the face, shoulders, and upper chest. No hallucinatory or visionary phenomena was reported at either low or high dose dynorphin ingestion. A 1999 study published in the Journal of Pharmacology and Experimental Therapeutics also administered dynorphin intravenously into human subjects at virtually identical dose levels (0.12 & 0.5 mg/kg) as Rick Strassman’s DMT study (0.05, 0.1, 0.2, and 0.4 mg/kg). This study also reported no hallucinatory activity with most subjects simply reporting “pins and needles” sensation, warmth, and/or observable flushing. To close out the paragraph Nichols once again wonders “out loud” why a researcher that is interested in studying the physiological functions of DMT isn’t focused on endorphins.
Nichols: A most critical aspect lacking in the discussion was a practical understanding of receptor pharmacology. 5-HT has a 10-fold higher affinity for the 5-HT2A receptor than DMT (PDSP Ki Database). Even if we accept that DMT is present at half the levels of 5-HT in cortex under normal physiological conditions, the combination of higher 5-HT levels and higher affinity of 5-HT for the target receptor indicate that DMT will not be engaging the receptor to any appreciable degree at baseline conditions. During asphyxiation, as the authors’ previous work shows, and as they interpret data here, levels of serotonin increase over 20-fold compared to only a 6-fold increase for DMT (Dean et al. Fig 4A), further widening this gap. At these comparative levels, with the 10-fold higher affinity of serotonin, 5-HT2A receptors would be saturated with serotonin and engagement of receptors by DMT in the presence of that much serotonin (and/or N-methylserotonin) would essentially be zero.
JC: It’s not clear if Nichols is attempting to throw doubt on the data provided by Dean by stating, “even if we accept that DMT is present at half the levels of serotonin in the cortex under normal physiological conditions”. Nevertheless the 5-HT2A receptor assumption by Nichols has already been addressed. According to the post by Hamilton Morris blocking the 5-HT2A receptor from DMT will not change the experience so this entire argument by Nichols could easily be invalid.
Nichols: There are additional issues with experimental design and interpretation of the data presented. For example, why was microdialysis performed in the visual cortex rather than the frontal cortex, where behaviors are mediated? Why was there no validation of RNAScope results with antibodies? mRNA levels do not necessarily correlate with expressed protein levels, and to state conclusively that the enzymes INMT and AADC are co-expressed in the same cells and synthesize DMT requires validation of the presence of the enzyme proteins themselves. The statement that “DMT would be the only monoamine whose biosynthesis takes place within the cerebral cortex where it may directly influence cognitive functions of the brain” is patently false. It has been known for years that monoamine neurotransmitters, including serotonin and N-methyltryptamines, are synthesized locally within the cerebral cortex where they can influence behaviors.
JC: Nichols questions why the microdialysis sampling took place in the visual cortex rather than the frontal cortex? I would presume that based on interest in the hallucinatory phenomena associated with near death experiences that measurements in the area of the brain coinciding with vision and/or visionary states would be a logical point of measurement.
Nichols: Perhaps most curious, in pinealectomized animals, the peak supposedly representing 5-HT is significantly blunted in comparison (Figure 4A & B). Why is that? The pineal gland does not regulate 5-HT levels in the brain and there is no expectation that the absence of this gland would alter cortical 5-HT levels after cardiac arrest. Further, two other un-identified peaks in the HPLC trace show the most significant increases after cardiac arrest (Figure 4B). What are these peaks? The authors do not address these discrepancies, but rather only compare serotonin to DMT in pinealectomized animals.
JC: A 2002 study published in the Proceedings of the National Academy of Sciences (which took place at the Borjigin lab) showed that the pineal gland unequivocally regulates 5-HT levels in the brain. Yes, it’s clear that 5-HT is synthesized locally throughout the brain but that fails to preclude the pineal gland secretory rate as having an effect on the levels. A 1985 study in The International Journal of Neuroscience observed significant decreases in the levels of 5-HT in three regions of the brain following pinealectomy… the hypothalamus, midbrain and hippocampus. A 1987 study in the journal Revista Espanola de Fisiologia observed that pinealectomy induced significant decreases in 5-HT levels in the hypothalamus and midbrain. A 1996 study in the journal Neurochemistry International also found evidence that pinealectomy decreased 5-HT in the hypothalamic nuclei and the ventromedial hypothalamic nuclei which was normalized by exogenous melatonin administration. It seems clear that melatonin deficiency can lead to suppressed levels of serotonin (5-HT) in certain regions of the brain.
Nichols: To be very clear, we are not arguing that DMT is not produced in the cortex of the rat. Rather, even with the production of amounts of DMT indicated by the authors’ data, the higher levels of serotonin, and potentially N-methylserotonin, are much more likely to induce a behavioral response through the 5-HT2A receptor. The “brainstorm” of additional neurochemicals may also be relevant to altered consciousness, and in addition, suggests the potential role of dynorphin or other endorphins, which were not measured, cannot be discounted. As Dean et al. wisely conclude, “It is unknown whether the concentrations of DMT reported in our study at cardiac arrest can elicit the effects of an exogenous psychedelic dose of DMT…” And, “the conscious states reported by NDE survivors may involve contributions from several of the other neurotransmitters found to surge at cardiac arrest in our prior rodent study.” Exactly our point here!
JC: Once again… Nichols is alluding to the notion that serotonin and potentially N-methylserotonin can act as hallucinogens. It would be wonderful to show actual data other than a mouse wiggling his little head.
Nichols: Science aside, a real problem with this report is that it is being taken up by the popular culture media and widely spread to a lay audience as now established dogma. Without a critical reading of the publication, advocates for the importance of endogenous DMT in the brain will and are saying, “see, we told you so.” Unfortunately, it only serves to propagate a pseudoscience meme. If we take the “politics” of DMT out of the equation, and simply examine the data presented, the publication by Dean et al. certainly is interesting and suggests additional directions to explore scientifically, but does not meet the bar for either claim that DMT is at functional levels in the cortex comparable to serotonin or is the “near death” neurotransmitter.
JC: The term pseudoscience was used. Geez…
Overall this critique of Jon Dean’s paper was a regurgitation of past work by Nichols. He failed to acknowledge important findings such as the same enzyme (INMT) that he used to make the statement of “huge amounts of DMT in the lungs” was found throughout 3 parts of the human and rat brain. This completely changes the notion that DMT levels cannot reach “physiological relevant” levels in the brain which was the basis for his initial argument regarding the pineal gland. The fact that a hallucinogenic molecule (DMT) is circulating in cerebral extracellular fluid at similar levels to commonly studied neurotransmitters serotonin, dopamine, and norepinephrine changes the conversation entirely. The mental framework of Nichols regarding how much DMT levels should fluctuate in the periphery to indicate a modulation of the experience cerebrally is a bit strange. In an August podcast on Psychedelics Today, Nichols made the following statement regarding DMT and the near death experience, “It just doesn’t make sense to me. Unless someone can prove it… you know that’s fine, I don’t have a problem if you can get somebody who is dying and measure the plasma concentrations loaded with DMT and you go “Oh Wow!” I don’t know where that came from. But you know… I’m (inaudible) that they’re willing to accept it but there just aren’t any experiments that would be reasonable.”
Why a person would expect a pharmacological equivalent surge in the periphery while it’s been shown that much like serotonin, DMT is likely produced locally and utilized locally is beyond me. If the term pseudoscientific should be thrown around, it should be utilized to describe a hypothesis that has no bearing on physiological reality. The rational perspective is that DMT likely plays a role in modulating a hallucinatory experience being that it is… a hallucinogen. Is it the sole molecule causing the experience? Obviously not. I don’t believe that Dean, Borjigin, Strassman, or Barker have ever alluded to that notion of a singular trigger based on a basic understanding of dynamic neurochemistry. The fact that the body also produces 5-MEO-DMT and monoamine oxidase inhibitors (a combination that has been warned to be extremely potent), also provides the possibility that extremely high pharmacological equivalent levels of these compounds is unnecessary to induce a significant modulatory effect of an experience.
(Neurochemical alterations are akin to fluctuations on a sound mixer. Different channel upregulation and downregulation coincide with changes in perception.)
As we cited in our initial rebuttal of Nichols, even Strassman’s study of injecting exogenous DMT into humans intravenously induced a robust effect of upregulating release of multiple chemicals in the periphery. It’s clear that even exogenous DMT does not act singularly so it would be silly for anyone to claim that dynorphin, LSD, psilocybin, or any compound for that matter acts as such.
The critique by Nichols comes off like an attempt to dissuade the public from recognizing that the recent finding by Dean and Borjigin is significant rather than as an honest scientific review. He seems more preoccupied by “fighting the media narrative” than he does in acknowledging the new discoveries and engaging in rational discourse regarding the new found data. His initial premise that DMT cannot be produced in sufficient amounts to have any physiological relevance is no longer valid. This was a point that Nichols never acknowledged and instead rerouted his argument to 5-HT2A affinity now claiming that regardless of DMT levels, receptor activation is not possible. This is disappointing in light of operating objectively and remaining consistent in scientific discourse. You don’t move the goal posts when the data surpasses your initial argument. The data has produced a new set of facts as follows:
Fact: DMT levels increased 600% in the brain following cardiac arrest
Fact: The enzymes to synthesize DMT are found in the cerebral cortex, choroid plexus, and pineal gland of humans and rats.
Fact: Extracellular brain levels of DMT are similar to serotonin, dopamine, and norepinephrine during normal waking hours.
The interpretation of these facts is up to the consumer but if you look at them objectively, they seem rather significant when compared to the prior speculative narrative of “pineal gland releasing a burst of DMT to induce an experience”. The bar has obviously been raised by this recent study and Nichols’ critique seems stuck in 2017. My criticisms of the Dean paper would be based on the fact that it could have been split up into 3 papers. One of them could have focused on the finding of INMT throughout the mammalian brain. The second paper could have focused on presenting the findings of extracellular brain DMT levels being comparable to neurotransmitters levels. The third paper could have presented the findings of increased levels of DMT in the visual cortex following cardiac arrest. The issue with the increased DMT levels is that the fluctuations were not measured in the same manner as the 2015 “brain storm” study which took place with minute to minute measurements. This added some confusion to the interpretation of the results. The combining of all these facets into one paper added a bit of confusion in terms of the interpretation for some people.
Going forward future studies will need to include measurements of 5-MEO-DMT, Bufotenin, and endogenous monoamine oxidase inhibitor fluctuations during 24 hour circadian rhythm studies, sleep stage studies, extended darkness exposure, fasting, and changing respiration rhythms. In addition, further exploration regarding DMT’s affinity for trace amine-associated receptor 1 (TAAR1) and this receptor’s potential role in regulating hallucinatory activity should be undertaken. A more theoretical study would include lucid dreaming and measuring the brain activity of people ingesting DMT within the dream during this experience. There is much more to uncover with the “Endohuasca” system and more to explore.
Let Nichols carry out the dynorphin studies. If he believes it’s that important he can do the work himself just like the Borjigin lab is doing the DMT work themselves. Emotions can tend to cloud judgment and in this case, emotions got the best of Nichols’. He fails to acknowledge new information in an attempt to alter the narrative but makes himself look a bit jaded in the process.
Report Card for David Earl Nichols:
- Failed to acknowledge the INMT finding in the cerebral cortex, choroid plexus, and pineal gland of humans and rats.
- Criticized Dean for focusing on DMT while interjecting dynorphin as a replacement research molecule.
- Cited the vast array of neurotransmitter surges following asphyxia in an attempt to frame endogenous DMT’s role as minimal yet citing dynorphin as a potential explanation
- Assumed that DMT primarily acts upon the 5-HT2A receptor when this has not been proven
- Claimed that any amount of DMT produced is incapable of inducing effect due to a lack of 5-HT2A affinity compared to serotonin
- Speculated that serotonin is hallucinogenic at elevated levels without ample evidence
- Showcased an inability to adjust one’s argument once new data has been brought to light making one’s past argument obsolete
- Falsley claimed that the pineal gland has no effect on brain 5-HT levels
- Exuded an emotional vendetta against the media which has no place in scientific discourse with other scientists
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