A recent increase in the rate of cannabis use by American adolescents and young adults has been compounded by greater drug availability and enhanced societal acceptance. As the movement towards legalization gains momentum, some researchers and clinicians have become increasingly concerned about negative physical and mental health outcomes associated with cannabis use, particularly in young people. In a recent review of the literature, Volkow and colleagues identified major depressive disorder (MDD) as a key outcome associated with cannabis use and misuse. In addition to depression, cannabis use and misuse pose numerous risks for suicidal thoughts and behaviors (STB). Given the relatively common nature of these psychiatric outcomes, if cannabis use truly contributes to MDD and STB, the public health impact of cannabis, particularly if recreational use is legalized, could be substantial. In response to PAS-14-020, encouraging population-based research on social, behavioral, and health outcomes of marijuana involvement, this 3-year application utilizes existing data (as encouraged by the PAS) and comprehensively examines the relationship between cannabis involvement, MDD and STB using longitudinal analyses at both the state- and person- levels. Using nationally representative state-level data, Aim 1 will examine whether key aspects of medical marijuana policies that are known to influence cannabis use as well as cannabis use characteristics are associated with MDD and STB, as well as state-level data on suicide completion, after accounting for confounding factors. Utilizing an individual-level developmental perspective, Aim 2 will employ data from three large and ethnically diverse datasets of twins and siblings (baseline N=8561) that span early adolescence (age 12-15) to young adulthood (ages 17-25), to examine the longitudinal relationship between cannabis involvement, MDD and STB using between-group (e.g. cannabis users vs. non-users) and within-person across-time approaches. Finally, given robust support for heritable influences on cannabis involvement, MDD and STB, Aim 3 will use data on 13,791 adult twins to examine whether after accounting for the genetic overlap (which we have demonstrated) between cannabis involvement, MDD and STB, there is an elevated likelihood of MDD and STB in twins who report cannabis involvement (ever, early, frequent and problem use) relative to their unexposed co-twin. The use of complementary state- and person-level analyses will allow us to fully examine which aspects of cannabis involvement specifically influence MDD and STB with longitudinal data affording tests of causation and reverse-causation as well as shared liabilities. This integrative approach will inform policy discussion regarding key sources of morbidity and mortality associated with cannabis use and misuse.