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N,N-dimethyltryptamine (DMT) is neither formed nor retained in serotonin terminals in the rat brain

Mikael Palner, Elisabeth Kolesnik, Christina Baun, Sandra N. Poetzsch, Paul Cumming

Neuropharmacology February 9, 2026 DOI: 10.1016/j.neuropharm.2026.110874 (opens in new tab)

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Characteristics Experimental study Peer reviewed
Population Rat brain
Interventions pargyline probenecid escitalopram dihydrotetrabenazine DMT+harmine
Dose 1 mg/kg each
Duration 210 minutes
Topics Serotonin 5-MeO-DMT DMT
Keywords Harmine Endogeny Pargyline Metabolite Harmaline Monoamine neurotransmitter Iproniazid Probenecid Endocrinology Pharmacology Monoamine oxidase inhibitor Reuptake Synaptosome Metabolism Dopamine Catabolism Transporter Biochemistry Central nervous system
Key findings No endogenous DMT was detected in rat brain, even after monoamine oxidase inhibition, and the data do not support DMT acting as a co-transmitter with serotonin.

Abstract

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. 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 minutes following DMT+harmine administration. The peak DMT concentration occurred at 45 minutes and peak 3-IAA levels at 60 minutes after DMT+harmine administration, with nearly complete washout of exogenous DMT at 210 minutes. 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. • Following injection, DMT shows rapid brain uptake and clearance. • DMT accumulated more in the frontal cortex than in the cerebellum. • Blocking serotonin reuptake transporter did not change DMT levels. • No endogenous DMT was detected in the brain, even when MAO-A was blocked. • The current data do not support DMT as a co-transmitter in serotonin.

Comparable studies

Other experimental studies on 5-MeO-DMT, most cited first.

Study Year Design Participants
Short term changes in the proteome of human cerebral organoids induced by 5-MeO-DMT. Human cerebral organoids 2017 Experimental study
Bufo alvarius: a potent hallucinogen of animal origin. Bufo alvarius toad venom 1994 Experimental study
Prospective examination of synthetic 5-methoxy-N,N-dimethyltryptamine inhalation: effects on salivary IL-6, cortisol levels, affect, and non-judgment Volunteers 2019 Within-subjects experimental study n = 11
Unmasking of a neonatal somatovesical reflex in adult cats by the serotonin autoreceptor agonist 5-methoxy-N,N-dimethyltryptamine. Adult cats 1990 Experimental study n = 10
Studies on the Mechanism of Action of Monoamine Oxidase: Metabolism of N,N-Dimethyltryptamine and N,N-Dimethyltryptamine-N-Oxide 1962 Experimental study

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Serotonin 5-MeO-DMT DMT