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Does the Human Brain Make DMT?

Does the human brain make DMT?
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N,N-dimethyltryptamine, or DMT, is one of the most powerful psychedelics on the planet.  What’s more, it’s a very simple compound that is found throughout the natural world.  Even our bodies produce it.  What is it doing inside us?  Does the human brain make DMT?  And, if so, might this endogenous source of a powerful psychedelic be responsible for religious experiences throughout the ages?

The Pineal Gland

One part of the brain has received much attention when it comes to mystical states of consciousness; the pineal gland.  About the size of a pea, the pineal gland sits in the middle of the brain.  Unlike most structures in the brain, which come in pairs, there is only one pineal gland.  These features made it the basis of much speculation in esoteric systems that existed before the advent of the scientific method.  From Ancient Egypt to Descartes, the pineal gland was considered to be something special, perhaps even the seat of the soul.  For Descartes, in particular, the pineal gland was the place in the brain that the immaterial soul interacted with the physical body.

The Spirit Molecule

In his book DMT: The Spirit Molecule, psychiatrist and pioneering psychedelic researcher Rick Strassman revived these ideas regarding the pineal gland, and made the link to DMT.  Before studying DMT, Strassman had studied the related compound and the main product of the pineal gland, melatonin.  After observing the dramatic effects of DMT in his subjects, he became interested in the centrality of the pineal gland in esoteric traditions of the past. His DMT subjects had vivid experiences of being transported to another realm that was populated by entities and often felt oddly familiar. These experiences seemed to mirror experiences of a spirit world or afterlife that have occurred throughout time, especially in near-death experiences

What if these experiences were the result of a spike in DMT produced by the brain?  Could the pineal gland in particular be responsible?  If so, might this explain the obsession with the pineal in the esoteric schools of thought?  According to Strassman, “it would really tie a nice, neat, bow around a lot of esoteric physiological speculation over millennia. But still, it isn’t established yet.”

DMT in the Pineal Gland

In 2013, Professor Jimo Borjigin of the University of Michigan lab put this idea to the test.  Lead researcher Steven Barker analyzed the chemicals present in the pineal gland of the rat.  As is often done in medical science, rodent brains were used to investigate what occurs in the brains of mammals in general, rather than trying to work with human brains.  In keeping with the DMT-pineal theory, they found that DMT was indeed present in the pineal gland.  This seemed like a slam-dunk for the theory, but there was one problem; there wasn’t very much.

How Much DMT Is Needed to Trip?

In 2017, Professor David Nichols, a leader in the field of psychedelic psychopharmacology, gave a presentation on the evidence for the DMT-pineal hypothesis at the conference Breaking Convention.  After a request from the audience, he later wrote up his critique as a paper.  Nichols argues that there’s nowhere near enough DMT in the pineal gland to have any psychoactive effects, meaning that pineal DMT cannot be responsible for religious and near-death experiences.  According to Nichols:

“The main function of the pineal gland is to produce melatonin. It produces micrograms of melatonin over 24 hours. If it can’t produce milligrams of melatonin, which is its main product, it certainly can’t produce milligrams of DMT. If you believe the stuff that Strassman and his collaborators have published based on his clinical studies, you would need to give a bolus of something like 25 milligrams to humans to get them into that so-called “DMT space”. Now, if it’s released directly in the brain you might need less than 25 milligrams. But clearly it’s far beyond the capacity for the pineal gland to produce that much DMT.”

Beyond the Pineal Gland

In 2019, Jimo Borjigin’s lab returned to the topic with an incredible series of experiments.  Lead researcher Jon Dean removed the pineal from rats and found that it didn’t reduce DMT levels in the brain overall.  Combined with the fact that so little DMT is found in the pineal, the evidence doesn’t stack up well for the DMT-pineal theory.  The pineal was never the thing of most significance, however.  Just because the pineal may not be involved, it doesn’t mean that other parts of the brain aren’t producing and being affected by DMT.  The core idea, that DMT might underlie spontaneous religious experiences, had survived this particular experiment.

What About the Rest of the Brain?

In the same study, the researchers measured levels of DMT in other parts of the brain.  In the cerebral cortex, the wrinkled outer surface of the brain where psychedelics typically have their effects, they found DMT.  DMT was measured in concentrations similar to other neurotransmitters, like serotonin and dopamine.  The DMT was found at a concentration of around 0.5 nano Molar (nM), half a billionth of a mole, which is a standard unit of concentration.  Neuroscientist Andrew Gallimore and Rick Strassman had previously collaborated in order to simulate how DMT concentrations might be reliably controlled in an experimental setting and found that a concentration of around 300nM is required for a full DMT trip to “DMT space”.  Could the concentration of DMT in the brain increase 600 fold in situations of mortal threat, producing the near-death experience?

Near Death Changes in DMT

Jon Dean and Jimo Borjigin went on to test this idea directly by measuring the levels of DMT in the rat brain during cardiac arrest.   Remarkably, they found that there was a spike in DMT at death, as would be expected if DMT produced near-death experiences.  The maximum increase was 10 fold above the average baseline, from 0.5nM to 5nm.  While this falls short of the dramatic 600 fold increase that would be necessary if the baseline level is similar in humans, there’s no ruling out that DMT levels might be different in the human brain.  What’s more, the brain might be more sensitive to DMT during the near-death state.  According to Jimo Borjigin:

“During near-death states, the brain activity that supports non-essential activities, such as walking, is severely reduced. So far scientists have studied experiences when people are fully awake, when they have many other types of brain activity going on. So in order to have a psychedelic experience, you need high levels of DMT that rise above the other noise that our brain is generating. At the near-death state, the level of DMT needed to contribute to a near-death experience may not be at the same level as for normal people having a normal psychedelic experience.”

DMT in Humans

What can this research in rats tell us about whether DMT is present in the human brain?  As mammals, it’s likely that a lot of the physiology is similar between rats and humans. However, there may also be differences.  According to David Nichols “you might measure some transmitter level in rats, and it may or may not translate into humans”.  Unfortunately, it’s not so easy to directly measure DMT in the human brain. “You can measure DMT in humans, but you don’t see much in blood plasma. If you want to measure it in cerebrospinal fluid, you have to do a lumbar puncture. And so not a lot of people were really excited about getting a spinal fluid tap. So it’s more difficult.” Another option is to do some detective work, and hunt down the enzymes that produce DMT. Where they are present there should also be DMT.

How to Make DMT

DMT is closely related to serotonin.  The raw material our body works with to produce both of these chemicals is an essential amino acid called tryptophan.  Our body cannot make tryptophan so it must be consumed through one’s diet–bananas and chocolate are particularly high in tryptophan.  Tryptophan itself is derived from a compound called ‘indole’ and the psychedelics that are produced from tryptophan retain the basic indole structure.  A specific enzyme removes a group of carbon, oxygen, and hydrogen atoms, known as a carboxyl group, from the tryptophan.  This “decarboxylation” transforms tryptophan into tryptamine – the suffix found in dimethyltryptamine. 

From this, we get all of the tryptamine psychedelics – DMT, psilocybin, 5-MeO-DMT being some of the most well known.  To get from tryptamine to dimethyltryptamine, you have to add methyl groups.  A methyl group is a compound derived from methane and consists of three hydrogen atoms bound to a carbon atom.  If one is added, you get N-Methyltryptamine (NMT).  If you add two, you get N,N-dimethyltryptamine (DMT).

DMT Production in the Human Brain

We all consume tryptophan in our diets.  We all have the enzyme that converts tryptophan to tryptamine, aromatic-L-amino acid decarboxylase (AADC).  The final step that gets you the biosynthesis of DMT from tryptamine is the addition of the two methyl groups.  The enzyme that transfers the methyl groups onto tryptamine, a compound with an indole structure, is called indolethylamine-N-methyltransferase (INMT).  Where there is AADC and INMT, there should also be DMT.  In the study discussed above, Jon Dean and Jimo Borjigin looked for AADC and INMT in the human brain and found it in the neurons of the cerebral cortex.  According to Jimo Borjigin:

“We showed neurons in the cortex contain both enzymes that are essential for DMT production. We believe that the DMT we detected in the brain is produced by those neurons in the cortex.”

Does DMT Have a Function in the Brain?

So it seems that DMT is most-likely produced in the human brain.  That doesn’t tell us what it’s doing there, however.  What might its function be?  Rick Strassman entertains the idea that it might function as a neurotransmitter.  “I think the presence of DMT in the brain is way more interesting than DMT in the pineal.  The concentrations of DMT in the brain are comparable to serotonin and dopamine, which points to the possibility of a DMT neurotransmitter system.  That would be completely mind-blowing, to start to speculate about what the role would be of a DMT neurotransmitter system in the mammalian brain.”

Jimo Borjigin also argues that DMT may act as a neurotransmitter: “At the time when we wrote the papers we did think that DMT could be a neurotransmitter.  To confirm that hypothesis, we’d have to demonstrate this storage mechanism.”  While skeptical that DMT acts as a neurotransmitter, David Nichols agrees that the lack of a storage mechanism is the key issue for this idea. He says: “Neurotransmitters are stored in vesicles in the neurons, they’re there to be released. As far as we know, DMT is not stored in this way.” Nichols argues that DMT may not have any function in the human brain at all. He goes on to say:

“There are things called secondary metabolites, they don’t play a direct functional role in brain physiology.  If it’s produced, it’s probably just a byproduct of fact that you have enzymes there that do it. We have lots of byproducts in living organisms that are produced that aren’t necessary for the survival of the organism and, as far as we know, don’t play a major role. There’s no evidence that we need DMT. There have been arguments that maybe it binds to the sigma receptor and has an antioxidant function. However, the affinity for the Sigma receptors is not high enough, and you don’t have concentrations high enough.”

Future Research

One thing all seem to agree on is the need for future research.  Starting several decades ago as speculation, the idea that DMT might play a role in the normal function of the brain has stood up well to experimental evidence.  Despite it being difficult to test directly, the evidence all points to it being present in the human brain.  The main problem for the idea that it plays a functional role, however, is how little there is of it.  It’s entirely possible that the DMT is a mere by-product of the physiological acidity of the brain.  With one of the world’s most powerful psychedelics likely lurking in your brain right now, however, the possibility that something more meaningful might be going on is very tantalizing.  For now, we’ll have to wait for the evidence to come in.

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