How psychedelic drugs generate altered states of consciousness while promoting enduring neuroplasticity remains a fundamental question in neuroscience with therapeutic implications. Here, we used quantitative phosphoproteomics in neural cultures to map intracellular signaling responses to serotonergic and non-serotonergic psychedelics. These compounds induced extensive remodeling of phosphorylation networks encompassing kinases, GPCRs, growth factor receptors, and epigenetic regulators. We uncovered a distinct phosphoproteomic signature that discriminates hallucinogenic from their non-hallucinogenic analogs, implicating pathways associated with metabolic regulation and neuroplasticity. Among these, phosphorylation of FOXK2, a glycolytic regulator, was specifically increased by hallucinogenic psychedelics. Functional validation confirmed that glycolytic activity is exclusively induced by this compound class. Our results define molecular architectures linking receptor activation to metabolic and structural plasticity, providing a framework for understanding the molecular basis of psychedelic action.