A Persistent Theory Meets Rigorous Testing
For decades, the idea that the human brain naturally produces dimethyltryptamine — the powerful psychedelic compound known as DMT — has captivated researchers, psychedelic enthusiasts, and neuroscientists alike. The hypothesis gained particular traction through popular culture and speculative scientific writing, with proponents suggesting that endogenous DMT might explain near-death experiences, dreaming, mystical states of consciousness, and other phenomena at the boundary of understood neuroscience.
Central to this theory is the notion that DMT functions as a natural signaling molecule or co-transmitter alongside serotonin in the brain. If true, this would mean that one of the most potent psychedelic substances known to science is not just an exotic plant alkaloid but a routine part of normal brain chemistry, produced and stored in the same neurons that regulate mood, sleep, appetite, and cognition through the serotonin system.
A new study published by researchers from the University of Southern Denmark and Bern University Hospital has now subjected this hypothesis to one of its most rigorous tests to date — and the results are strikingly negative.
What the Researchers Actually Tested
The research team set out to answer two fundamental questions. First, does the rat brain naturally produce detectable levels of DMT? And second, can DMT be taken up and stored in serotonin-releasing neurons through the same transport mechanisms that handle serotonin itself?
These questions matter because the endogenous DMT hypothesis depends on both conditions being true. For DMT to function as a co-transmitter alongside serotonin, it would need to be synthesized in the brain in meaningful quantities and then stored in synaptic vesicles within serotonin neurons, ready for release alongside serotonin during normal neural signaling.
The team analyzed multiple brain regions using highly sensitive quantitative detection methods capable of identifying trace amounts of DMT. To maximize their chances of finding the compound, they also used enzymatic inhibitors that block DMT's metabolic breakdown by monoamine oxidase. If the brain were producing even small amounts of DMT that were being rapidly degraded, blocking that degradation should cause detectable levels to accumulate.
The Results: No DMT Detected
Despite these methodological advantages, the researchers found no detectable endogenous DMT in adult rat brains. Even with the metabolic breakdown pathway blocked, the compound simply was not present in measurable quantities. As the lead researcher stated plainly, DMT is neither formed nor stored in serotonin terminals in the rat brain.
The second part of the experiment was equally revealing. When the researchers administered DMT externally, they tested whether it could be absorbed into serotonin neurons via the serotonin transporter (SERT) and stored in synaptic vesicles via the vesicular monoamine transporter (VMAT2) — the two transport proteins that normally handle serotonin uptake and storage. The administered DMT was not retained in serotonin terminals, indicating that even if DMT were somehow present in the brain, it lacks the molecular properties needed to enter and persist within the serotonin system through these established pathways.
What This Means for the Endogenous DMT Hypothesis
The findings do not prove that the brain never produces any DMT under any circumstances. They do, however, substantially narrow the terrain on which the endogenous DMT hypothesis can stand. If DMT is not detectable in rat brains even when its breakdown is blocked, any naturally occurring levels would be, in the researchers' words, extremely low — too low to plausibly function as a signaling molecule in the way the hypothesis proposes.
The inability of DMT to enter serotonin neurons through normal transport mechanisms is perhaps the more significant finding. Even if future research were to identify trace DMT production in the brain, the compound would need a way to get into and out of neurons in a controlled manner to function as a neurotransmitter. The absence of this uptake capability suggests that DMT does not participate in the serotonin system's normal signaling machinery.
This does not mean DMT has no biological significance whatsoever. The compound could conceivably operate through mechanisms entirely outside the classical serotonin system — perhaps involving other cell types, other brain regions, or specific physiological states such as extreme stress, oxygen deprivation, or the dying process that were not examined in this study. But the specific version of the hypothesis that places DMT alongside serotonin as a co-transmitter in the brain's primary mood-regulating system has now lost a critical piece of its empirical foundation.
Context Within Psychedelic Research
The study arrives at a time of unprecedented investment in psychedelic research. Clinical trials of psilocybin, MDMA, and ketamine for depression, PTSD, and other psychiatric conditions have produced promising results, and several regulatory approvals are either granted or pending in multiple countries. DMT itself is under investigation as a potential therapeutic agent, with early-stage clinical trials exploring its effects on depression and other conditions.
For this therapeutic research, the new findings change very little. DMT's profound effects on consciousness and its potential therapeutic value do not depend on whether the brain naturally produces the compound. Aspirin was a transformative medicine long before anyone understood the endogenous prostaglandin system. What matters for therapeutic development is whether DMT can be administered safely and whether it produces clinically meaningful outcomes — questions that clinical trials are actively addressing.
But for basic neuroscience, the study is a valuable corrective. It demonstrates the importance of testing popular hypotheses with rigorous methodology rather than allowing them to persist on the basis of plausibility and cultural appeal. The endogenous DMT theory has circulated for decades, often presented with far more confidence than the underlying evidence warranted. By applying modern analytical techniques to the question, this research team has provided the scientific community with the kind of clear, negative result that is essential for redirecting research attention toward more productive avenues.
Looking Forward
Future investigations into endogenous DMT may shift focus to non-serotonergic cell types, peripheral tissues, or the specific physiological extremes that the theory's proponents have long pointed to as contexts where DMT production might spike. The pineal gland, often cited in popular accounts as the brain's DMT factory, remains a target of interest despite limited supporting evidence from prior studies.
What is clear, however, is that the simple version of the story — the brain makes DMT, stores it in serotonin neurons, and releases it to produce altered states of consciousness — does not hold up under scrutiny. The science of psychedelics continues to advance rapidly, but it must do so on the basis of what the evidence actually shows rather than what we might wish it to show.
This article is based on reporting by Medical Xpress. Read the original article.
