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Yet, orphaned neuropeptide systems and receptors (oGPCR), which have no known cognate receptor or ligand, remain understudied in drug discovery and development. Orphan neuropeptides and oGPCRs are abundantly expressed within the brain and represent an unprecedented opportunity to address brain function and may hold potential as novel treatments for disease. Here, we describe the current literature regarding orphaned neuropeptides and oGPCRs implicated in AUD. Specifically, in this review, we focus on the orphaned neuropeptide cocaine\u2010 and amphetamine\u2010regulated transcript (CART), and several oGPCRs that have been directly implicated in AUD (GPR6, GPR26, GPR88, GPR139, GPR158) and discuss their potential and pitfalls as novel treatments, and progress in identifying their cognate receptors or ligands.<\/jats:p>","DOI":"10.1111\/bph.16301","type":"journal-article","created":{"date-parts":[[2023,12,11]],"date-time":"2023-12-11T06:04:13Z","timestamp":1702274653000},"page":"595-609","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Orphan peptide and G protein\u2010coupled receptor signalling in alcohol use disorder"],"prefix":"10.1111","volume":"181","author":[{"given":"Roberta Goncalves","family":"Anversa","sequence":"first","affiliation":[{"name":"Florey Institute of Neuroscience and Mental Health  Melbourne VIC Australia"},{"name":"Florey Department of Neuroscience 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