The study tested whether the psychedelic compound N,N-dimethyltryptamine (DMT) exists naturally in the mammalian brain and acts as a co-transmitter with serotonin. In rats, blocking monoamine oxidase with pargyline did not allow detection of endogenous DMT, while blocking acidic metabolite transport with probenecid slightly elevated the DMT metabolite 3-indoleacetic acid, likely from tryptamine. Exogenous DMT was rapidly taken up and cleared from the brain, with peak concentrations at 45 minutes and near-complete washout by 210 minutes. Blocking serotonin reuptake or vesicular monoamine transporters did not alter DMT levels. The results do not support the hypothesis that DMT is an endogenous co-transmitter with serotonin.
The mammalian brain may contain an endogenous pool of the psychedelic N,N-dimethyltryptamine (DMT), possibly acting as a co-transmitter with serotonin. In rats, inhibiting monoamine oxidase with pargyline did not make endogenous DMT detectable, while probenecid slightly elevated the acidic metabolite 3-indoleacetic acid (3-IAA), suggesting formation from tryptamine, especially in the striatum. After administering DMT plus harmine, peak brain DMT occurred at 45 minutes and peak 3-IAA at 60 minutes, with nearly complete washout by 210 minutes. Escitalopram did not alter exogenous DMT or 3-IAA disposition, and dihydrotetrabenazine slightly increased 3-IAA in some regions. The results do not support an endogenous DMT pool or retention of exogenous DMT in serotonin terminals.