Alcohol Use Disorder (AUD) is a global social burden, with alcohol being the most prevalent psychoactive substance used by older individuals. Alcohol intake is a recognized carcinogen and is regulated by alcohol dehydrogenases (ADHs) and aldehyde dehydrogenases (ALDHs), with activity and expression determined by genetic factors. Alcohol withdrawal challenges include tremors, diaphoresis, anxiety, sleeplessness, hallucinations, and convulsions. Alcohol also stimulates cholinergic interneurons and increases the sensitivity of 5-HT3 receptors within the nucleus accumbens, which play a critical role in reward and addiction. Chronic alcohol consumption alters the mesolimbic dopaminergic system, an important neural pathway involved in reward processing. First-line pharmacotherapies for AUD include oral naltrexone and acamprosate, disulfiram, and nalmefene. Off-label therapies include baclofen, topiramate, gabapentin, ondansetron, and cytisine. Understanding altered neuronal signaling pathways by alcohol helps identify effectors involved in mitigating central actions and offers new therapeutic perspectives for alcohol addiction rehabilitation.

Alcohol is a prevalent psychoactive substance and a risk factor for developing injuries and non-communicable diseases, representing a significant health and economic burden. Alcohol involves numerous molecular pathways. Its metabolism is regulated by alcohol dehydrogenases and aldehyde dehydrogenases; it also stimulates cholinergic interneurons, increasing the sensitivity of 5-HT3 receptors, while chronic alcohol consumption alters the mesolimbic dopaminergic system involved in reward processing. The treatment of alcohol use disorder (AUD) is essential to manage complex patients, following an evidence-based approach. The aim of this narrative review is to provide a clear and practical summary to support and assist healthcare professionals in the Italian context. Approved pharmacological treatments for AUD include oral naltrexone and acamprosate, sodium oxybate, disulfiram, and nalmefene. Off-label therapies include baclofen, topiramate, gabapentin, pregabalin, ondansetron, and cytisine. A more informed clinical and practical approach that understands the altered neuronal signaling pathways is essential for offering effective, efficient, appropriate, and safe therapeutic algorithms for complex patients with alcohol use disorder. A comprehensive framework should include integrated treatments with a personalized approach.