Abstract
The serotonergic psychedelic N,N-dimethyltryptamine (DMT) produces rapid antidepressant effects in preclinical and early clinical studies. Therapeutic benefits have been linked to sustained neural plasticity, including adult neurogenesis in rodents. Whether brief DMT exposure engages proliferative responses in human neural stem cells (NSCs) remains unresolved. Using human iPSC-derived NSCs, we found that 24 h DMT treatment increased proliferation in a concentration-dependent manner (half-maximal effect at 59.7 nM) and upregulated G1 cell-cycle regulators. DMT also shifted trophic gene expression, decreasing neurotrophin-3 while increasing nerve growth factor and brain-derived neurotrophic factor (BDNF) transcripts and intracellular BDNF protein. After washout, DMT-primed NSCs formed larger neurospheres, with progenitor and early neuronal marker composition matching controls by day 10. These findings demonstrate that brief DMT exposure is sufficient to engage proliferative and neurotrophin-associated responses in human NSCs at concentrations consistent with those reported for DMT-induced plasticity across other systems.
