UCLA

Alcohol use disorder (AUD) is a prevalent and debilitating condition that has substantial social, psychological, and medical consequences. Despite its significant public health impact, only three medications are approved by the U.S. Food and Drug Administration (FDA) for the treatment of AUD, and no new medications have been approved in over two decades. Thus, there is a critical need to improve the processes for developing and evaluating novel pharmacotherapies. The current dissertation comprises two complementary lines of research. The first line of research examines methodological considerations in AUD pharmacotherapy clinical trials, including the selection of efficacy endpoints (Chapter 1), the influence of trial length on observed medication effects (Chapter 2), and the use of cigarettes and cannabis during an AUD clinical trial (Chapter 3). Together, these studies inform key design considerations for future AUD pharmacotherapy trials. The second line of research examines peripheral biological markers associated with AUD and treatment response, using data from a randomized clinical trial of the neuroimmune modulator ibudilast. Specifically, it investigates peripheral inflammatory and intestinal permeability markers as moderators of ibudilast treatment response and their associations with clinical characteristics (Chapter 4) and models the relationship between changes in alcohol consumption and peripheral inflammatory markers during treatment (Chapter 5). Collectively, this dissertation contributes to the development and evaluation of pharmacotherapies for AUD by informing key aspects of clinical trial design and advancing understanding of the biological processes relevant to AUD and its pharmacological treatment.