Serotonergic G-protein-coupled receptors (GPCRs), including the 5-HT2A receptor (5-HT2AR) and 5-HT2CR, are key regulators of cortical signaling pathways and promising targets for neurotherapeutic drug discovery. Researchers from the University of Texas System have developed AB-0124, a 5-HT2AR allosteric ligand, and JPC-0323, a dual 5-HT2AR/5-HT2CR allosteric ligand, with the aim of overcoming issues with direct agonists of these receptors for treating substance abuse disorders, like cocaine use.