For many years, researchers have questioned whether the psychedelic compound dimethyltryptamine (DMT) is produced naturally in the brain and if it might act as a signaling substance similar to serotonin. A recent study provides new evidence that challenges this idea.
A team from the University of Southern Denmark and Bern University Hospital found no detectable evidence of naturally occurring DMT in the serotonin system of adult rat brains. Their findings, published in Neuropharmacology, indicate that if DMT is present in the brain, it does not appear to function as a typical co-transmitter within serotonergic neurons in adult rats.
A Long-Standing Hypothesis
Certain plants produce DMT, a well-known psychedelic compound and the active ingredient in the traditional ceremonial drink ayahuasca. Structurally, it is similar to serotonin, a neurotransmitter involved in mood, perception, and cognition.
Earlier studies have shown that mammals possess the enzyme indolethylamine N-methyltransferase (INMT), which can synthesize DMT. After this discovery, researchers began speculating that the body produces DMT and stores it in serotonin-releasing nerves.
Based on this possibility, some researchers have suggested that DMT might function as a natural signaling molecule in the brain. To investigate this hypothesis, the research team measured DMT levels in various brain regions of adult rats. They used highly sensitive quantitative methods designed to detect even trace amounts of the compound.
No Detectable Endogenous DMT
“We found no evidence of naturally occurring DMT in the adult rat brain – even when we inhibited its breakdown – nor did we observe that administered DMT was stored in serotonin neurons,” said Mikael Palner, associate professor at the University of Southern Denmark and co-author of the study.
The researchers began by testing for measurable amounts of DMT under normal conditions. Next, they blocked DMT’s breakdown, expecting this would increase and extend its presence if it existed naturally. Despite these efforts, they did not detect any endogenous DMT in the brain regions they examined.
The team also tested whether serotonin-releasing nerve terminals absorbed and stored externally administered DMT. Specifically, they examined whether DMT interacted with the serotonin transporter (SERT) or the vesicular monoamine transporter 2 (VMAT2), both of which package and release neurotransmitters. Their results showed no significant retention of DMT in serotonin-releasing nerve terminals.
Narrowing the Search
“Our findings strongly indicate that DMT is neither formed nor stored in serotonin terminals in the rat brain, and that any natural levels must be extremely low or regulated by mechanisms outside the brain’s serotonin system,” Palner said.
These findings suggest that DMT is unlikely to act as a typical signaling molecule within the serotonin system of adult rats. However, these results do not fully resolve the question. If DMT does have a biological role, it may involve other cell types, tissues, or particular conditions that the researchers did not examine in this study. Additionally, the lack of detectable DMT in this model does not rule out the possibility that very low or short-lived concentrations might exist below the limits of current detection methods.
Even so, these findings help clarify an ongoing scientific debate. The inability to detect endogenous DMT in serotonin neurons, even under conditions intended to reveal its presence, narrows the possible natural, biological roles that DMT could play in the brain.
As interest in psychedelics continues to expand, studies like this highlight the importance of testing longstanding scientific ideas with careful quantitative methods. Such work helps refine the search for where, and if, naturally occurring DMT may play a role in mammalian neurobiology.
Austin Burgess is a writer and researcher with a background in sales, marketing, and data analytics. He holds a Master of Business Administration, a Bachelor of Science in Business Administration, and a Data Analytics certification. His work combines analytical training with a focus on emerging science, aerospace, and astronomical research.