Calcitonin Gene-Related Peptide Signalling in Alcohol Use Disorders: A Scoping Review.

ISSUE: Alcohol use disorders (AUD) represent a major global health burden, and currently available pharmacological treatments show limited and heterogeneous efficacy. Calcitonin gene-related peptide (CGRP) is a pleiotropic neuropeptide involved in stress regulation and neuroimmune signalling, and is an established therapeutic target in migraine. CGRP signalling may also be involved in alcohol-related mechanisms, raising interest in its potential relevance for AUDs. APPROACH: We conducted a scoping review of original studies investigating CGRP and CGRP-related pathways in the context of alcohol exposure and AUDs. A systematic literature search was performed in PubMed, Embase, Cochrane Library, PsycINFO and Scopus. Animal and human studies published in English were included and synthesised narratively. KEY FINDINGS: Thirty studies met the inclusion criteria, including 26 animal studies and 4 human studies. IMPLICATIONS: Preclinical evidence indicates that CGRP plays a context-dependent role in AUD-related mechanisms, modulating stress-related drinking, withdrawal-associated adaptations and alcohol-induced nociceptive sensitisation rather than directly driving alcohol consumption. In peripheral tissues, CGRP exerts protective effects against ethanol-induced gastric and pulmonary injury. Human studies were limited and largely observational and showed altered CGRP biology in advanced alcohol-related liver disease, suggesting a compensatory or homeostatic role. CONCLUSIONS: CGRP represents a biologically relevant but complex target in AUDs, with both potential therapeutic and protective roles depending on the clinical context. Anti-CGRP therapies may warrant exploration in carefully selected scenarios, such as alcohol-related headache or stress-associated symptoms during withdrawal in non-cirrhotic patients. Given the homeostatic functions of CGRP, any pharmacological modulation should be cautiously evaluated.