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

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.

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.

Thirty studies met the inclusion criteria, including 26 animal studies and 4 human studies.

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.

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.