PROJECT SUMMARY/ABSTRACT This K01 award will provide the support for the attainment of Dr. Kimberly Goodyear’s long-term goals of contributing to treatment discoveries for individuals with an alcohol and smoking comorbidity and advancing the addiction field with rigorous research techniques. As outlined in this K01 proposal, the training activities will afford Dr. Goodyear with excellent mentorship, training and experience to: 1) To learn how to conduct research involving a clinical trial with individuals with alcohol use disorder (AUD); 2) To learn how to conduct research involving a clinical trial with smokers; 3) To gain knowledge working with oxytocin (OXT) as a novel treatment for AUD smokers; 4) To have a background in neuroendocrine pathways to assess the relationship of OXT with the etiology of alcohol and cigarette use; 5) To learn advanced functional magnetic resonance imaging (fMRI) analysis; and 6) To learn multilevel modeling statistical methods. This K01 proposal is especially salient given the serious health consequences associated with and the prevalence of alcohol drinking and smoking. There is a lack of current treatment options for this comorbid group that signals an exigent need for developing efficacious medications. Recent preclinical and human research suggests that OXT may be a potential treatment for alcohol, smoking and other addictive behaviors due to its anxiolytic, stress reducing and anti- craving effects. This proposed research seeks to examine the behavioral and neural substrates of intranasal OXT compared to placebo on alcohol cue-induced alcohol and cigarette craving in AUD smokers. Non treatment-seeking AUD smokers will be recruited to participate in a between-subjects, placebo-controlled, randomized pilot fMRI study. Participants will undergo an fMRI scan in conjunction with an alcohol-olfactory cue-reactivity task. Secondary assessments will include alcohol and cigarette craving, alcohol and cigarette consumption, physiological measures (heart rate and blood pressure) and mood measures. A team of qualified mentors will support Dr. Goodyear with this comprehensive research plan. This proposed research will address the substantial need for developing new pharmacological treatments by advancing the science knowledgebase to improve interventions for individuals who co-use alcohol and cigarettes. This five-year career development plan will facilitate Dr. Goodyear’s transition to an independent clinical researcher and will assist in laying the groundwork for future treatment strategies and grant applications generated from the findings of this research.