In Vivo Long-Term Kinetics of Radiolabeled N,N-Dimethyltryptamine and Tryptamine

Abstract

N,N-dimethyltryptamine (DMT), a strong psychodysleptic drug, has been found in higher plants, shamanic hallucinogenic beverages, and the urine of schizophrenic patients. The aim of this work was to gain better knowledge on the relationship between this drug and hallucinogenic processes by studying DMT behavior in comparison with tryptamine. Methods: 131 I-labeled DMT and tryptamine were injected into rabbits. g-Camera and biodistribution studies were performed. Brain uptake, plasma clearance, and renal excretion were assessed for each indolealkylamine. Results: DMT and tryptamine showed different behavior when brain uptake, residence time, and excretion were compared. Labeled DMT entered the brain 10 s after injection, crossed the blood-brain barrier, and bound to receptors; then it was partially renally excreted. It was detected in urine within 24 h after injection and remained in the brain, even after urine excretion ceased; up to 0.1% of the injected dose was detected at 7 d after injection in the olfactory bulb. In contrast, tryptamine was rapidly taken up in the brain and fully excreted 10 min after injection. Conclusion: To our knowledge, this is the first demonstration that exogenous DMT remains in the brain for at least 7 d after injection. Although labeled DMT and tryptamine behave as agonists for at least 5-hydroxytryptamine 2A receptor, 5-hydroxytryptamine 2C receptor, trace amine-associated receptor, and s-1 putative receptor targets, binding to the latter can explain the different behavior of labeled DMT and tryptamine in the brain. The persistence in the brain can be further explained on the basis that DMT and other N,N-dialkyltryptamines are transporter substrates for both the plasma membrane serotonin transporter and the vesicle monoamine transporter 2. Furthermore, storage in vesicles prevents DMT degradation by monoamine oxidase. At high concentrations, DMT is taken up by the serotonin transporter and further stored in vesicles by the vesicle monoamine transporter 2, to be released under appropriate stimuli. Moreover, the 131 I-labeling proved to be a useful tool to perform long-term in vivo studies. Incont inuation of our research on labeled compounds, such as phenethylamines, tryptamines, and harmines and native Amazonian N,N-dimethyltryptamine (DMT)-containing beverages such as ayahuasca (1-3) (also called ayahoasca and hoasca tea), we now report the in vivo behavior of DMT and tryptamine.DMT (Fig. 1) is a psychodysleptic compound that has been found in a variety of higher plants (4,5) and organisms (6), brain and other tissues of mammals and humans (6,7), and the urine of schizophrenic patients (2,8-10).As a hallucinogen, DMT was reported as a direct postsynaptic agonist at 5-hydroxytryptamine 2A (5-HT 2A ) receptors and a partial agonist at 5-hydroxytryptamine 2C (5-HT 2C ) receptors (11). Recently, biochemical, physiologic, and behavioral experiments demonstrated that DMT is an endogenous agonist at s-1 receptors (s-1Rs) (12); the hypothetical signaling scheme triggered by this binding ha...

Neuropharmacology of N,N-dimethyltryptamine

“…However, DMT could still be detected at 2 and 7 days (0.1% of initial dose) post administration (Vitale et al, 2011). In the same study, tryptamine was eliminated within 10 min.…”

“…Once uptake and storage of DMT has been completed, it can remained stored in vesicles for at least 1 week and can be released under appropriate stimuli (Vitale et al, 2011). Through these three steps, peripheral synthesis of DMT, consumption of DMT-containing plant matter, or systemic administration of DMT can influence central nervous system functions (Frecska et al, 2013).…”

Tryptamine and dimethyltryptamine inhibit indoleamine 2,3 dioxygenase and increase the tumor‐reactive effect of peripheral blood mononuclear cells

“…This assumption is supported by the following findings: (i) the transcriptional expression of the enzymes responsible for the synthesis of TRY and DMT has been described in diverse mammalian tissues; 19 (ii) DMT is actively transported and accumulated in the brain and storage vesicles; 20 and (iii) DMT injected in rabbits persists in the brain at micromolar concentrations. 21 In conclusion, we identified a previously unknown inhibitory activity of TRY and DMT on IDO activity that contributed to a more effective tumor-reactive response by immune cells.…”

“…However, in some circumstances, it is conceivable that the concentration of these compounds could be enough to provide IDO inhibition. This assumption is supported by the following findings: (i) the transcriptional expression of the enzymes responsible for the synthesis of TRY and DMT has been described in diverse mammalian tissues; (ii) DMT is actively transported and accumulated in the brain and storage vesicles; and (iii) DMT injected in rabbits persists in the brain at micromolar concentrations …”

Determination of N,N-dimethyltryptamine in Mimosa tenuiflora inner barks by matrix solid-phase dispersion procedure and GC–MS

“…1. To confirm the identity of the compound, a 1 H and 13 C NMR spectra of the isolated chemical were generated and are in agreement with others previously described for the DMT in the literature [2,21,26,27]. …”