Emerging pharmacological targets for alcohol use disorder

Abstract

Alcohol Use Disorder (AUD) remains a challenging condition with limited effective treatment options; however new technology in drug delivery and advancements in pharmacology have paved the way for discovery of novel therapeutic targets. This review explores emerging pharmacological targets that offer new options for the management of AUD, focusing on the potential of somatostatin (SST), vasoactive intestinal peptide (VIP), glucagon-like peptide-1 (GLP-1), nociceptin (NOP), and neuropeptide S (NPS). These targets have been selected based on recent advancements in preclinical and clinical research, which suggest their significant roles in modulating alcohol consumption and related behaviors. SST dampens cortical circuits, and targeting both the SST neurons and the SST peptide itself presents promise for treating AUD and various related comorbidities. VIP neurons are modulated by alcohol and targeting the VIP system presents an unexplored avenue for addressing alcohol exposure at various stages of development. GLP-1 interacts with the dopaminergic reward system and reduces alcohol intake. Nociceptin modulates mesolimbic circuitry and agonism and antagonism of nociceptin receptor offers a complex but promising approach to reducing alcohol consumption. NPS stands out for its anxiolytic-like effects, particularly relevant for the anxiety associated with AUD. This review aims to synthesize the current understanding of these targets, highlighting their potential in developing more effective and personalized AUD therapies, and underscores the importance of continued research in identifying and validating novel targets for treatment of AUD and comorbid conditions.