ABSTRACT Alcohol use disorder (AUD) is significant public health concern. Stress is a central component in modern theories of alcohol use, and stress is intimately related to drinking for many individuals. There are a number of approved medications for AUD, but the majority of individuals do not respond to these medications and no medications address the role of stress. The current proposal looks affect alcohol use by targeting stress-related systems in the body through peroxisome proliferator-activated receptors (PPARs), which may effect stress reactivity, stress-induced alcohol craving, and alcohol use. Pioglitazone (Actos) targets PPARγ and is FDA- approved for treating individuals with diabetes and metabolic disorders. Promising results from both human trials and animal research suggest that pioglitazone holds great promising for addressing AUD, including preliminary data from our own research. The current proposal will attempt to expand on our preliminary findings targeting alcohol use among treatment-seeking individuals with AUD and elevated stress and/or anxiety with the following specific aims: 1) to assess if pioglitazone decreases stress reactivity and stress- induced craving in a human laboratory model; and 2) to assess if pioglitazone changes weekly psychometric reports of stress/anxiety, craving, and alcohol consumption. Notable strengths of the current proposal include: 1) targeting individuals with elevated stress/anxiety and AUD; 2) biological assessment of stress reactivity (heart rate, blood pressure, salivary cortisol); 3) a multi-dimensional assessment of alcohol craving incorporating relatively novel behavioral economic measures (i.e., alcohol demand, delay discounting); and 4) inclusion of powerful Bayesian statistical tools that are well suited for smaller samples, such as the current proposal.