Summary: For decades, the idea that the human brain naturally produces N,N-dimethyltryptamine (DMT)—often dubbed “The Spirit Molecule”—has been a cornerstone of psychedelic lore, linked to dreams and near-death experiences. However, a new studychallenges this popular narrative.
Using highly sensitive quantitative methods, researchers looked for endogenous DMT in the rat brain and investigated whether it could be stored in serotonin neurons. The results were definitive: even when the metabolic breakdown of the substance was blocked, no natural DMT was detected. The findings suggest that if DMT is a signaling substance, it doesn’t function within the brain’s classical serotonin system as previously speculated.
Key Facts
- No Detectable Levels: Researchers found no evidence of naturally occurring DMT in the adult rat brain, even after inhibiting the enzymes that usually break it down.
- Serotonin System Exclusion: The study proved that DMT is not stored or accumulated in serotonin-releasing nerve terminals, making its role as a “co-transmitter” unlikely.
- Highly Sensitive Testing: The team used trace-detection methods to ensure that even “micro-amounts” would be spotted; yet, the results remained negative.
- The “INMT” Enzyme: While mammals possess the enzyme (INMT) capable of synthesizing DMT, this study shows that possessing the machinery doesn’t mean the product is being actively manufactured in the brain.
- Narrowing the Search: The findings don’t rule out DMT in other tissues or specific physiological states (like birth or death), but they clarify that it is not a standard brain signaling substance.
Source: University of Southern Denmark
For decades, the idea that the human brain might naturally produce the psychedelic compound DMT has attracted considerable attention. It has been speculated that DMT could function as a natural signalling substance in the brain – possibly as a co-transmitter alongside serotonin.
Previous research has shown that mammals, including rats, possess the enzyme indolethylamine N-methyltransferase (INMT), which can synthesise DMT. However, it has remained unclear whether DMT occurs in the brain in measurable amounts.
Researchers at the University of Southern Denmark (Mikael Palner) and Bern University Hospital (Paul Cumming) have now examined whether the rat brain naturally contains DMT and whether the substance can be stored in the nerve cells that release serotonin.
– 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, says Mikael Palner, Associate Professor at the Department of Clinical Research and first author of the study.
Mikael Palner and his research group measured DMT in selected brain regions in adult rats.
What do the results mean?
– 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, explains Mikael Palner.
The findings make it less likely that DMT plays a role as a classical signalling substance in the serotonin system in adult rats.
If DMT has a biological function, it may be linked to other cell types, other tissues or specific physiological states that were not included in this study.
What is DMT?
N,N-dimethyltryptamine (DMT)
• A psychedelic compound that is also found in certain plants, and the active component in Ayahuasca.
• Chemically related to the signalling substance serotonin
• In popular culture, it has been linked to dreams and near-death experiences
• Can be synthesised in mammalian tissue via the enzyme indolethylamine N-methyltransferase (INMT)
Three questions for Mikael Palner about the study
What did you investigate in the study?
There is a long-standing debate whether the psychedelic compound DMT (N,N-dimethyltryptamine), also the active compound of the Ayahuasca, is a native compound in the mammalian brain, and possibly stored in serotonin neurons.
Here we used highly sensitive and quantitative methods to examine whether DMT is naturally available and additionally if DMT can be stored in serotonin‑releasing nerve terminals in the rat brain.
What is the key finding?
We found no detectable evidence that endogenous DMT exists in the adult rat brain, even after blocking its normal metabolic breakdown, a process that increases and prolong the availability of administrated DMT. We also saw no meaningful retention of administered DMT inside serotonin terminals.
How can the findings be used?
The findings clarify an ongoing scientific debate by showing that serotonin neurons are unlikely to store or accumulate DMT, and that the examined brain regions do not contain native DMT. This helps narrow the search for where DMT may originate or act in the brain, if it is at all present.
About the study
Method: The researchers analysed several brain regions in adult rats using quantitative methods capable of detecting trace substances.
They also examined whether administered DMT could be taken up and stored in serotonergic neurons via the serotonin transporter (SERT) and vesicular monoamine transporter 2 (VMAT2).
Funding: The study was supported by a grant from the Swiss National Science Foundation (Grant Number 320030 204978).
Key Questions Answered:
A: This study specifically looked at the adult rat brain’s serotonin system and found nothing. While it makes it less likely that the brain naturally pumps out DMT during normal activity, it doesn’t rule out its presence in other organs (like the lungs) or during very specific, unstudied physiological events.
A: This idea was popularized by Dr. Rick Strassman in the 1990s. The theory was that the pineal gland released a flood of DMT during intense moments. However, this new data suggests that the “hardware” for storing and releasing DMT like a traditional neurotransmitter simply isn’t there.
A: Our brains have receptors (like the 5-HT2A receptor) that evolved to respond to serotonin. Psychedelic DMT “hijacks” these receptors because its chemical structure is very similar to serotonin—not necessarily because the brain is waiting for its own “internal” DMT.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this neuroscience research news
Author: Marianne Becker
Source: University of Southern Denmark
Contact: Marianne Becker – University of Southern Denmark
Image: The image is credited to Neuroscience News
Original Research: Open access.
“N,N-dimethyltryptamine (DMT) is neither formed nor retained in serotonin terminals in the rat brain” by Mikael Palner, Elisabeth Kolesnik, Christina Baun, Sandra N. Poetzsch, and Paul Cumming. Neuropharmacology
DOI:10.1016/j.neuropharm.2026.110874
Abstract
N,N-dimethyltryptamine (DMT) is neither formed nor retained in serotonin terminals in the rat brain
Mammalian brain may contain an endogenous pool of the psychedelic substance N,N-dimethyltryptamine (DMT), which may act as a co-transmitter with serotonin (5-HT).
We tested the joint hypotheses that endogenous DMT would accumulate in rat brain after inhibiting monoamine oxidase with pargyline, whereas its acidic metabolite 3-indoleacetic acid (3-IAA) would accumulate after pretreatment with the inhibitor of acidic metabolic transport, probenecid.
We also tested the hypothesis that pretreatment with inhibitors of plasma membrane 5-HT uptake (escitalopram, ESC) or the vesicular monoamine transporter 2 (dihydrotetrabenazine, DTBZ) would reduce the retention in brain of exogenous DMT after administration of DMT + harmine (1 mg/kg each).
We first established the time courses of brain DMT, 3-IAA, and harmine concentrations for 210 min following DMT + harmine administration. The peak DMT concentration occurred at 45 min and peak 3-IAA levels at 60 min after DMT + harmine administration, with nearly complete washout of exogenous DMT at 210 min.
Endogenous DMT levels were below the detection limit of our analytic method, despite pargyline pretreatment, and endogenous 3-IAA was slightly elevated by probenecid treatment, suggesting formation from tryptamine, especially in striatum. ESC did not alter the disposition of exogenous DMT or its metabolite 3-IAA, whereas DTBZ slightly increased 3-IAA formation in some brain regions.
In summary, we could not detect an endogenous DMT pool in rat brain, and saw scant evidence of retention of exogenous DMT in 5-HT terminals.
