A Duke University-led team of scientists developed a synthetic molecule that selectively dampens the physiological rewards of cocaine in mice. The molecule, designated SBI-553, is an NTSR1 GPCR agonist that demonstrates fewer side effects than other drugs targeting the same receptor. Murine tests confirmed that the new molecule calmed drug-induced hyperactivity, dramatically reduced drug self-administration, and altered metabolic responses in the brain’s reward center.