New insights into how a mammalian brain naturally produces psychedelic DMT
A compelling new study has revealed how a mammalian brain can produce an incredibly powerful hallucinogen called DMT. The research shows the psychedelic is endogenously produced in a number of brain regions, including the visual cortex, and spikes in concentrations following an induced cardiac arrest.
For several decades the hypothesis that dimethyltryptamine, or DMT, was produced endogenously in the human body presented one of the most compelling mysteries in the field of psychedelic science. The presence of this extraordinarily powerful hallucinogenic molecule has been tracked in tiny amounts in a variety of bodily fluids, but where DMT is produced in a body, and why it's produced, are still unanswered questions.
Perhaps the most well-known researcher in the DMT field is a scientist named Rick Strassman. In the early 1990s he conducted a number of iconic experiments, administering DMT to human patients and chronicling the results in an influential book entitled DMT: The Spirit Molecule.
Strassman's work documented a compelling array of bizarre subjective experiences, but his overriding hypothesis was that DMT is produced in the pineal gland and released into the body during both dream and death states. One more extreme speculative hypothesis suggests the substance is flushed into the human body at the time of death for a yet to be explained reason. These ideas remained somewhat on the fringes of commonly accepted science for years until neuroscientist Jimo Borjigin came across Strassman's work while researching teaching notes.
"I said to myself, 'wait, I've worked on the pineal gland for years and have never heard of this,'" says Borjigin. "I thought if DMT is an endogenous monoamine, it should be very easy to detect using a fluorescence detector."
Borjigin contacted Strassman and set out to see if they could once and for all find explicit traces of DMT in a mammalian brain. The research led to an important paper, published in 2013, explicitly finding direct traces of DMT in the pineal gland of a rat for the first time.
The study of course raised a whole host more questions than it answered. How was the rat brain synthesizing DMT? Was this process localized to just the pineal gland? What function does this endogenous DMT production serve?
A new study from Borjigin, Strassman, and a number of other scientists has shed light on some of these questions, revealing how DMT is synthesized in a rat brain, and how levels of the hallucinogenic molecule curiously spike after a cardiac arrest is induced.
Two enzymes, known as INMT and AADC, are fundamentally needed to biosynthesize DMT. Using a novel technique called in situ hybridization, one of the most impressive discoveries outlined in this new paper is the description of specific cells in the rat brain that can express both INMT and AADC enzymes. This offers the first clear and plausible mechanistic explanation of how a mammalian brain could create DMT. Not only that, but this study describes these cells as being found in many parts of the brain, not only the pineal gland.
"With this technique, we found brain neurons with the two enzymes required to make DMT," says Borjigin. "They are also found in other parts of the brain, including the neocortex and hippocampus that are important for higher-order brain functions including learning and memory."
The research also fascinatingly revealed that DMT levels in the rat brain significantly increased after an experimentally-induced cardiac arrest. Although it was shown the DMT is generated in several parts of the brain, these cardiac arrest experiments noted distinct increases in DMT concentration in the visual cortex.
Replicating the experiment in animals without a pineal gland revealed no difference in cortical DMT levels. This interesting datapoint suggests the pineal gland is not a major DMT-producing part of the brain, contrary to Strassman's longstanding hypothesis, but the hallucinogenic molecule is in fact generated quite widely across different parts of the animal's brain.
As for translating these results to human brains, this initial study does reveal INMT-expressing neurons in the human brain. Prior study does suggest the human brain also contains neurons that express AADC, but further work will be needed to uncover whether there are singular human brain cells that co-express both enzymes.
While this work does significantly advance our knowledge of how a mammalian brain could endogenously produce DMT, the question of why it may produce this molecule is still a complete mystery. Due to the rapid metabolic activity of DMT in a human, it is an incredibly difficult molecule to detect, but this study is a valuable addition into the field of psychedelic neuroscience, establishing that rats do produce this hallucinogenic molecule and that it is not improbable to suggests human brains do the same.
"We don't know what it's doing in the brain," says Borjigin. "All we're saying is we discovered the neurons that make this chemical in the brain, and they do so at levels similar to other monoamine neurotransmitters."
The new research was published in the journal Scientific Reports.
Source: University of Michigan