Traceless Fluorescent Labeling of Endogenous 5-HT2A Receptors

Treatments for mental health conditions such as depression have remained stagnant for decades. Psilocybin and other psychedelic drugs represent a beacon of hope, showing great promise to advance psychiatric medicine. Psychedelics profoundly alter human consciousness through activation of 5-HT2A receptor proteins in the brain, and these effects are correlated with therapeutic outcomes. While extensive resources are being invested to understand psychedelic mechanisms of action, currently available tools are insufficient to visualize native 5-HT2A receptors in the living brain. This research proposal aims to develop a new small molecule probe that permanently illuminates 5-HT2A receptors in living cells and brain tissue without modifying the receptor function or expression. We anticipate this cutting-edge tool to enable researchers a new way to study the therapeutic and physiological role of 5-HT2A receptors, empowering innovation and ultimately leading to more effective treatments for mental health disorders.