My research program focuses on how alcohol and other recreational drug use taxes human physiological systems and undermines health, even in the absence of addiction. We define substance use as a physiological stressor akin to poor diet, insufficient sleep, and sedentary behavior that forces bodily systems (e.g., cardiovascular, hepatic, immune) away from their homeostatic set points in dose-dependent ways. Our ongoing studies assess whether the behaviors of our daily life ‘pile up’ that is, whether exposure to minor stressors, including alcohol intoxication and insufficient sleep, if frequent enough, accumulates, eventually precipitating illness and disease in body systems, particularly the cardiovascular system.