Alcohol dependence (AD) is a major cause of disability, morbidity and mortality world-wide. Current treatment involves various forms of psychosocial treatment and, more recently, pharmacological interventions. However, most patients with AD do not receive treatment and few receive medication, in part because of the modest efficacy of FDA- approved drugs. There is a general consensus that new medications for AD need to be developed that have greater effectiveness and/or new spectrums of activity, e.g. anxiolytic properties. Many recent human studies have found that intranasal administration of oxytocin (OT) has numerous prosocial effects and reduces anxiety. Clinical trials testing high dose intranasal OT for up to 8 weeks found no adverse effects. Several studies indicate that OT may be an effective treatment for AD. Animal experiments have shown that OT blocks tolerance formation to alcohol and markedly decreases withdrawal symptoms. We recently published the results of a randomized, double-blind pilot study in alcohol-dependent subjects undergoing medical detoxification with CIWA score-driven PRN lorazepam treatment. BID intranasal OT was dramatically more effective than placebo in decreasing CIWA scores, the total amount of lorazepam required to complete detoxification, and anxiety measures. Our findings are the first evidence that OT treatment blocks alcohol withdrawal in humans. This is of clinical importance as standard treatment of alcohol withdrawal with benzodiazepines is effective but, unlike OT, may maintain high levels of sedative- hypnotic tolerance that could increase vulnerability to relapse by sustaining alcohol craving, heightened anxiety and diminished ability to cope with stress as well as enabling consumption of large quantities of alcohol upon relapse. We also found that OT administration significantly decreased alcohol consumption and anxiety in P (alcohol-preferring) rats subjected to repeated alcohol deprivation combined with stress, an animal model of relapse. Other animal studies have shown that OT is potently anxiolytic. This evidence suggests that OT treatment may decrease drinking in alcohol- dependent patients by reducing anxiety, vulnerability to stress and perhaps alcohol tolerance. The proposed research represents a unique, translational collaboration between a basic behavioral neuroscientist with expertise in OT (Dr. Cort Pedersen) and an expert in the treatment of AD with extensive experience in conducting clinical trials (Dr. JC Garbutt). We propose a randomized, double-blind, placebo-controlled trial of intranasal OT treatment in 50 alcohol-dependent patients starting early during inpatient medical detoxification and extending for 12 weeks after discharge during which subjects' drinking will be assessed at regular intervals. The overall goal of the project is to determine whether OT treatment in a real world sample of heavy drinkers (patients seeking medical detoxification at a mental health center) is truly effective in decreasing withdrawal symptoms and, in the outpatient setting, reducing drinking. This project has potential to significantly advance the pharmacological treatment of AD. Also, confirming that OT blocks alcohol withdrawal and demonstrating that OT decreases drinking, anxiety, and craving in the outpatient setting would be a triumph of translational research that would establish CNS OT as an important new front for research on the pathophysiology of AD.