Heimia salicifolia, also known as Sinicuichi or the Sun Opener, is a flowering plant in the loosestrife family (Lythraceae) with a rich, yet obscure and incompletely understood, ethnobotanical history of traditional use in Central and South America. The Sun Opener owes its name to the yellowing and darkening of the visual field that is experienced under its influence, with prominent psychedelic effects that include auditory hallucinations along a highly enhanced memory retrieval, which allows users to revisit prenatal events. Despite these and other potentially therapeutic properties, such as euphoria, analgesia, and heightened clarity of mind, H. salicifolia has been significantly understudied. Consequently, the fundamental pharmacological agents responsible for its psychedelic effects remain unknown, and potential next-generation psychedelics unexplored. This project delves into the ethnopharmacology of H. salicifolia through a neurobiological lens; and has generated preliminary evidence suggesting that its psychedelic nature is linked to a neuromodulatory response that stems from the presence of specific combinations of alkaloids, in close interplay with traditional methods of preparation. By focusing on the neuropharmacology and signaling mechanisms of these alkaloids downstream to several receptors, we are systematically dissecting Sinicuichi's effects on gene expression and different types of synaptic plasticity while exploring functional selectivity as a potential explanation for the emergence of this nuanced psychedelic experience. This project emphasizes the remarkable potential of incorporating traditional knowledge for studying molecules of natural origin and, ultimately, hopes to unveil new targets and chemotypes to contribute to developing novel, safer, and more effective treatments for psychiatric and neurological disorders.