Psychedelic Substituted Phenethylamine Alters Human Neural Progenitor Cell Morphology, Proliferation, and Survival

Psychedelic Substituted Phenethylamine Alters Human Neural Progenitor Cell Morphology, Proliferation, and Survival

Alvin Sherman Library

Examining how psychedelic substituted phenethylamines affect neural plasticity is key to understanding harms and potential medical implications of recreational drugs. The microtubule cytoskeleton has been proposed to modulate the effects of phenethylamines as a downstream effector and through scaffolding mechanisms. Microtubules play a crucial role in neurite outgrowth, protein transport, and synaptic stability in cells. Our group has shown that specific psychedelic substituted phenethylamines (25B-NBF, 25C-NBF, and DMBMPP) alter microtubule formation in a dose-dependent manner. As these phenethylamines limit microtubule capacities, they may impact cytoskeletal-mediated neural plasticity. This study’s purpose is to determine if substituted phenethylamines, 25B-NBF, 25C-NBF, and DMBMPP affect human neural progenitor cell (hNPC) morphology, proliferation, and survival. hNPCs were exposed to 50 μM of each of the substituted phenethylamines or vehicle control for 24 hours. Immunostaining assays were conducted to evaluate neurite formation and cellular morphology. Cell cycle kinetics and proliferation were assessed with EdU assays, while TUNEL assays were used to examine programmed cell death. Cells treated with 25B-NBF and 25C-NBF showed no significant change in morphology, proliferation, or cell death compared to vehicle-treated controls. In contrast, DMBMPP-treated cells displayed altered morphology, a significant decrease in proliferation, and a significant increase in cell death. These findings suggest that DMBMPP treatment alters cell morphology, decreases cell proliferation, and increases cell death, ultimately impacting neural plasticity. Identifying how substituted phenethylamine-induced changes in microtubule stability alter hNPCs may contribute to our understanding of how psychedelics produce different effects on behavior and identify therapeutic targets to treat their adverse effects.