A Single Dose of 5-MeO-DMT Stimulates Cell Proliferation, Neuronal Survivability, Morphological and Functional Changes in Adult Mice Ventral Dentate Gyrus

“…However, while longer exposure durations could have induced changes in these properties, our data are aligned with findings that daily exposure to 100 μg of 5‐MeO‐DMT for 21 days failed to induce a change in membrane potential, AHP duration, or amplitude in adult hippocampal dentate gyrus neurons (Lima da Cruz et al. 2018). Thus, DMT may not induce changes in core intrinsic membrane properties underlying the AHP or membrane potential even with prolonged exposure; however, the caveat remains that DMT and 5‐MeO‐DMT are not chemically identical and effects on intrinsic properties could be cell type specific and may depend on the particular neuronal phenotype under investigation.…”

“…Specifically, the frequency and amplitude of sEPSCs in layer V pyramidal neurons in rodent brain slices obtained 24 h after 1 and 10 mg/kg DMT treatment were increased (Ly et al 2018). In another study, a significantly higher amplitude and frequency of sEPSCs were noted in the hippocampal dentate gyrus when brain slices were recorded 3 days post treatment with 5-MeO-DMT (Lima da Cruz et al 2018). Effects of DMT on plasticity have been further shown by structural studies indicating persistent changes induced by DMT in dendritic growth, spine density, and synaptogenesis in the PFC and hippocampus, with effects also observed in human cortical organoids (Ly et al 2018;Morales-Garcia et al 2020;Dakic et al 2017).…”

“…Compared to fluoxetine, DMT produced stronger effects on both neurogenesis and behavior, highlighting its rapid and possibly more targeted mechanism of action. Together with previous results using 5-MeO-DMT [40], as well as harmala alkaloids like harmine and tetrahydroharmine which also promote neurogenesis [24, 52], our findings suggest that multiple components of the ayahuasca brew may converge on shared neurogenic and plasticity-enhancing pathways. These synergistic effects support a polypharmacological framework for psychedelic-induced circuit repair.…”

“…We chose 5-MeO-DMT ( 28 ) and 6-F-DMT ( 29 ) as electron-rich and electron-poor DMT analogues, respectively. Compound 28 has been reported to promote neuritogenesis in the dentate gyrus and alleviate symptoms of depression and anxiety in humans. , Compound 29 is predicted to be nonhallucinogenic, as fluorination of DMT analogues is known to attenuate their hallucinogenic potential . When compared directly, isoDMT analogues 6 and 13 performed identically to 28 and 29 (Figure ), suggesting that SAR data related to neuronal growth obtained using derivatives of the isoDMT scaffold could be applied to derivatives of the DMT scaffold through analogy due to the isosteric nature of the two structures.…”