The research proposed here will translate findings from preclinical research and provide the
initial clinical evidence that orexin antagonism reduces motivation for cocaine, as well as
other cocaine-associated maladaptive behaviors in active cocaine users. This study will also
provide basic science information about the orexinergic mechanisms underlying the
pharmacodynamic effects of cocaine in humans. As such the outcomes will contribute to our
understanding of the clinical neurobiology of cocaine use disorder. Overall, the proposed
work seeks to expand the scope of current clinical neuroscience research on cocaine addiction
by focusing on orexin, which has strong preclinical evidence supporting its critical role in
addiction but remains unstudied in humans.