Furthermore, we highlight future directions to elucidate the interaction between the prefrontal cortex (PFC) and key intermediaries including ΔFosB, cAMP response element binding protein (CREB) and cyclin-dependent kinase 5 (CDK5) to highlight possible mechanisms that underlie stress-induced acceleration of the progression to a cocaine use disorder diagnosis. This evidence concerns the gene CREB1 and cocaine use disorder.