Orexin receptor antagonism for the treatment of opioid use disorder

Existing treatment options for opioid use disorder (OUD) face challenges that limit their efficacy.  Preclinical evidence implicates the orexin/hypocretin system in numerous aspects of OUD development and symptomology: opioid use, opioid-associated cue-driven drug seeking, and opioid withdrawal states that lead to relapse.  Studies indicate that selective and dual orexin receptor antagonists (SORAs and DORAs) may be treatments for OUD and other substance use disorders. Several DORAs have already been approved by the FDA for the treatment of insomnia, making their repurposing potentially straightforward.  Recent clinical trials have demonstrated multifaceted efficacy of DORAs for ameliorating opioid craving, withdrawal, and related sleep disturbances in individuals with OUD.

A recent review in Transational Psychology outlines the fundamental theories of orexin system function and relates orexinergic dysfunction to the disordered motivation and withdrawal states that characterize OUD, and provides an up-to-date evaluation of preclinical and clinical evidence supporting the efficacy of orexin receptor antagonism for the treatment of OUD.

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