Early use of addictive substances is a robust predictor of subsequent substance-related problems, including dependence. However, there is debate about whether policy and other interventions aimed at curbing early use would have significant effects on the development of dependence and related health problems over the long- term. The global aim of the studies proposed here is to use historical policy changes governing the age at which youth may legally purchase alcohol or tobacco as natural experiments to test the hypothesis that adolescent exposures may have very long-term effects on substance-use problems and substance-related morbidity and mortality in adulthood. Our recent work has established that minimum legal drinking age laws (MLDAs) may influence risk for substance use disorder, even among individuals in their 30s, 40s or 50s (Norberg et al. 2009). In this project, this approach will be extended to other long-term outcomes and a similar approach will be applied to policies restricting youth access to tobacco. Analyses will use existing epidemiological data sets, often nationally representative, with sample sizes in the range of tens to hundreds of thousands, enabling the study of heterogeneity of effects by race, sex or other variables. Econometric methods will be used to control for many observed and unobserved potential confounders. When possible, consistency of results across data sets will be examined. Specific Aims include 1.) To investigate the long-term effects of MLDA policy on binge drinking, other substance use, and co-occurring conditions and behaviors in adulthood 2.) To investigate the effects of laws restricting youth access to tobacco (YATT laws) on adult smoking behavior and adult drinking and drug use. Based on our preliminary results, as a sub-aim the hypothesis that YATT laws predict reduced rates of smoking among pregnant women will be tested. 3.) To examine morbidity and mortality effects of MLDA policy. Addiction to tobacco and alcohol are among the leading public health problems both in the U.S. and globally. The work proposed here has the potential to shed light on persistent effects of modifiable environmental risk factors for problems of clear public health relevance. Accomplishment of these aims will be facilitated by a strong-interdisciplinary team and a rich collaborative environment. PUBLIC HEALTH RELEVANCE: We intend to use historical policy changes governing adolescent access to alcohol and tobacco as natural experiments to study whether policy environments in which adolescents have easier access to alcohol and tobacco lead to elevated risk for addiction and related health effects later in adulthood. Addiction to tobacco and alcohol are among the leading modifiable causes of morbidity and mortality in the U.S. and globally; and these studies have the potential to shed light on unstudied long-term effects of these modifiable environmental risk factors for significant public problems.