Quantitative phosphoproteomics uncovers the signalling dynamics of hallucinogenic psychedelics.
bioRxiv : the preprint server for biology November 26, 2025 Sandra M. Martin-Guerrero, Marco Taddei-Tardón, Jessica L Maltman et al. preprint
Chemically diverse psychedelics trigger a coordinated reorganization of phosphorylation patterns across many proteins in neural cells. This global signaling response contains a distinct signature that separates hallucinogenic compounds from non-hallucinogenic counterparts of similar structure. Using a glycolysis-regulating transcription factor as an example, hallucinogenic psychedelics, but not their non-hallucinogenic analogues, enhance markers of glycolytic metabolism. These findings reveal that hallucinogenic and non-hallucinogenic psychedelics engage separable intracellular architectures, establishing a framework for understanding how different psychoactive compounds couple receptor activation to specific cellular states.