N,N-dimethyltryptamine (DMT) is neither formed nor retained in serotonin terminals in the rat brain
This animal study challenges a long-standing hypothesis that DMT is stored and released like serotonin in serotonergic neurons, narrowing where researchers should look for endogenous DMT production or function.
“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.”
The study does not prove the brain never produces DMT. Instead, it suggests:
If endogenous DMT exists, levels are extremely low or produced outside serotonergic neurons.
It might occur in other tissues, cell types, or physiological states not examined in this study.
It does show no detectable DMT in serotonergic neurons of adult rat brains and argues against it functioning as a serotonin co-transmitter.
Palner M, Kolesnik E, Baun C, Poetzsch SN, Cumming P. N,N-dimethyltryptamine (DMT) is neither formed nor retained in serotonin terminals in the rat brain. Neuropharmacology. 2026 May 15;289:110874. doi: 10.1016/j.neuropharm.2026.110874. Epub 2026 Feb 9. PMID: 41672133. Read Paper
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