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The relationship between childhood maltreatment and later substance use outcomes is relatively well documented in extant literature. However, these studies leave room for a persistent need to better understand how and why childhood maltreatment produces distinct health behavior outcomes, as well as the social mechanisms that drive these changes. Theoretically rooted in life course theory and the stress process theory, this paper aims to explore the differential effects of variations in maltreatment experiences (subtype, severity, timing) on adolescent substance use, as well as how family relationships and associations with drug-using friends potentially mediate this association. The data are drawn from the LONGSCAN project, a prospective study following children from early childhood to late adolescence. Implications of the findings and recommendations for future research will be further discussed.