DMT in the Brain

“Something in nature knows more chemistry than we do.”

N,N-dimethyltryptamine, DMT, is present in your body right now. It has been found in human blood, urine, cerebrospinal fluid, and brain tissue. It is structurally related to serotonin and melatonin. It is produced by the same biochemical pathway that produces serotonin. It is, in the technical sense, an endogenous compound: your body makes it.

What your body makes it for remains almost entirely unknown.

This is one of the most interesting unsolved questions in psychopharmacology, and it sits at the intersection of neuroscience, pharmacology, and the phenomenology of altered states in a way that makes it genuinely consequential rather than merely strange. The three-tier framework for evaluating claims in this area is essential: what is confirmed, what is plausible but unproven, and what is speculative.

Confirmed: DMT is present in human tissue. This was established definitively in the 1970s and has been replicated repeatedly. David Nichols's 2016 Pharmacological Reviews comprehensive review confirms the presence of endogenous DMT and documents its structural relationship to serotonin and the shared biosynthetic pathway. When administered exogenously, injected intravenously in Rick Strassman's FDA-approved studies at the University of New Mexico in the 1990s, or smoked, or consumed as part of ayahuasca, DMT produces dramatic alterations in consciousness that typically last between five and fifteen minutes (when smoked) or several hours (in ayahuasca, where MAO inhibitors from Banisteriopsis caapi prevent its rapid metabolism).

Plausible but unproven: the pineal gland as primary DMT production site. Serena Roney-Dougal, writing in the 2011 issue of Paranthropology dedicated to psi and psychedelic experience, presents the most detailed version of this hypothesis. The pineal gland, a small endocrine structure in the center of the brain, has been proposed by Strassman and others as the likely site of endogenous DMT synthesis, based on several converging lines of evidence: the pineal contains the enzyme machinery required for DMT synthesis, it is anatomically positioned in ways that might allow DMT to reach the brain's receptor systems without being metabolized before arrival, and the timing of certain peak pineal activity (near birth, near death, during REM sleep) correlates with the conditions under which people most commonly report spontaneous experiences resembling DMT states, near-death experiences, birth recall, and vivid dreams.

The hypothesis is physiologically plausible. It has not been confirmed. The specific claim that the pineal produces DMT in sufficient quantities to produce psychedelic effects in the brain requires measurement data that does not yet exist. It is not impossible. It is simply undemonstrated.

Speculative: the broader McKenna-Strassman framework in which endogenous DMT mediates naturally occurring mystical states, death experiences, and potentially psi phenomena. Terence McKenna and his brother Dennis, in True Hallucinations and its companion scientific paper, proposed that the La Chorrera experiment produced a catalysis of the brain's own DMT system, that what happened in the Amazon in 1971 was not simply the effect of externally administered tryptamines but an unlocking of an endogenous capacity. The psi and psychedelic experience literature, as documented by David Luke in Paranthropology's special issue, notes that psychedelics and psi phenomena show consistent co-occurrence across multiple cultural and experimental contexts, and proposes the shared neurochemical mechanism as a possible explanation.

This is genuinely interesting. It is not, by current evidence, more than that.

What the ayahuasca literature, the two Labate and Cavnar volumes published by Springer, adds to this picture is the therapeutic dimension. The beta-carbolines in Banisteriopsis caapi are MAO-A inhibitors, which is why orally administered DMT in ayahuasca produces a much longer experience than smoked DMT: the MAO enzymes that would otherwise metabolize DMT in the gut are blocked, allowing it to reach the brain. But harmine, one of those beta-carbolines, has an additional effect that has nothing to do with the DMT pathway: it inhibits DYRK1A, an enzyme involved in neurogenesis, and this inhibition promotes the growth of new neurons and new synaptic connections. The therapeutic effects of ayahuasca for depression, addiction, and trauma may therefore involve two parallel mechanisms: the DMT-mediated experiential component and the harmine-mediated neuroplasticity component, operating through different pathways simultaneously.

The Changa literature documents the practical consequence of this pharmacology: the addition of MAOI-containing herbs to smoked DMT extends the experience from five to fifteen minutes to thirty to forty-five minutes, and participants report qualitative differences in the character of the experience, more sustained, more integrated, with greater narrative coherence. Changa exists precisely because the DMT experience alone is too brief for the kind of processing that therapeutic benefit requires.

DMT is in your body. What it is doing there, and what it might be doing during your dreams and your deepest experiences and possibly your approach to death, remains genuinely unknown. The questions are specific enough to be scientific. The answers are not yet in. In the meantime, the most precise thing that can be said is what Terence McKenna said about the Amazon itself: something in nature knows more chemistry than we do.

Sources

• Nichols, D.E. Psychedelics. Pharmacological Reviews, 68(2) (2016)
• Roney-Dougal, S. in Hunter, J. (ed.) Psi and the Psychedelic Experience. Paranthropology, Vol. 2 No. 2 (2011)
• McKenna, T. True Hallucinations (1993)
• Labate, B. & Cavnar, C. (eds.) Ayahuasca Healing and Science. Springer (2021)