Psychedelic-inspired drug discovery using an engineered biosensor.
Cell April 28, 2021 Chunyang Dong, Calvin Ly, Lee E. Dunlap et al. 207 citations
A genetically encoded fluorescent sensor called psychLight, based on the 5-HT2A receptor structure, detects behaviorally relevant serotonin release and correctly predicts whether structurally similar 5-HT2AR ligands will cause hallucinogenic behavioral effects. Using psychLight, a non-hallucinogenic psychedelic analog was identified that produced rapid-onset and long-lasting antidepressant-like effects after a single administration. The sensor enables in vivo detection of serotonin dynamics, early identification of designer drugs of abuse, and development of non-hallucinogenic therapeutics targeting the 5-HT2AR.