Current Pharmacotherapies for Alcohol Use Disorder in Italy: From Neurobiological Targets to Clinical Practice

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.