Project Summary/Abstract Substance use disorders (SUD) disproportionately affect multiple vulnerable populations, including individuals with mental health problems. Although it had been long assumed that SUD risks are not elevated among individuals with autism spectrum disorders, recent publications, including those in JAMA, highlighted, on the contrary, a disproportionate vulnerability to SUD among youth and adults with autism spectrum disorder (ASD), as independently reported in several international studies. For example, in a study of individuals with SUD in Taiwan, the presence of ASD was shown to triple mortality rates, increase severity of SUD symptoms and escalate their progression. In the US, very little is known about the elevated vulnerability to SUD among youth and adults with ASD, potentially creating a “hidden” vulnerable population underserved by the current substance use treatment systems. The overall goal of the proposed study is to analyze the world’s largest healthcare data set, the US national Medicaid data, to (1) compare the likelihood of having various SUDs among individuals with and without ASD, aged 11 and older; and (2) analyze differences in SUD treatment usage and SUD severity among substance-using individuals with and without ASD. To identify malleable moderators of the above relationships, we will for the first time merge Medicaid patient with data on patients’ social determinants of health (e.g. social isolation and economic instability) from TransUnion, a national repository of individual-level socio-economic data (available only for adults). We will also test moderating effects of state policies regarding reimbursement of specific SUD and ASD interventions. More specifically, the proposed study will examine whether SUD prevalence, severity, patterns and SU- related adverse events are exacerbated by ASD status. It will also examine the role of social determinants of health, demographic factors, and state-level treatment policies in buffering or amplifying the effects of ASD on substance use related outcomes.