Suvorexant proposed to reduce cocaine motivation and maladaptive behaviors in active users

Despite existing pharmacotherapies for substance use disorders, relapse vulnerability remains a significant challenge, highlighting the need for novel therapeutic approaches. Current standard-of-care often falls short in addressing the complex neurobiology of addiction, particularly the persistent craving and motivation for drug seeking. Preclinical research has strongly implicated the orexin system (also known as hypocretin) in mediating reward, arousal, and stress responses, all of which are critical components of addiction. Specifically, orexin antagonism has shown promise in animal models by reducing drug-seeking behaviors. This proposed research aims to bridge the gap between extensive preclinical evidence and initial human clinical data for cocaine use disorder.

This proposed clinical study aims to translate preclinical findings into human evidence by investigating the effects of suvorexant in active cocaine users. The research will provide initial clinical evidence that orexin antagonism can reduce motivation for cocaine and other cocaine-associated maladaptive behaviors. Concurrently, the study will gather basic science information on the orexinergic mechanisms underlying the pharmacodynamic effects of cocaine in humans. This involves exploring how cocaine interacts with the orexin system in a clinical setting, which remains largely unstudied in human populations. The study design is intended to establish the foundational understanding necessary for future therapeutic development in cocaine use disorder.