GRANT NUMBER:  R01 AA019983-04S1

ABSTRACT:  Of great concern is that the use of multiple substances — polysubstance use — is widespread and represents a major challenge to prevention and treatment efforts. Approximately 80% of adolescent substance users consume two or more drugs simultaneously. These usage patterns confer greater health risks and negative consequences, and worse intervention outcomes. Despite the prevalence and potential risks, there are no reports on human adolescents could be located to help us more fully understand the range of neurodevelopmental predictors of polysubstance use or for its effect on the developing adolescent brain. The gap particularly applies to the dual use of alcohol and marijuana, the two most commonly initiated and simultaneously consumed drugs in adolescence, which may be especially impactful. An integrated, transdisciplinary model is proposed to understand the inherent linkages and temporal dynamics between factors consistently and strongly implicated in substance use initiation and escalation generally that are likely to be similarly involved in polysubstance abuse, perhaps with even greater strength and impact. Accordingly, our original specific aims have been expanded in this Administrative Supplement to include a focus on polysubstance abuse, allowing us to further investigate this issue (see additions in italics). Aim 1: Precursors. To identify the antecedent neurodevelopmental liability factors that predict initiation and escalation of alcohol use and polysubstance use (primarily alcohol and marijuana in this age group). History of stress exposures and genetic variants will be explored as potential moderators. Aim 2: Developmental Effects. To measure the impact of alcohol and the simultaneous use of alcohol and other addictive substances on the course of neurodevelopment and stress responsivity.

The Parent Study includes longitudinal measures of behavior and temperament, ECFs and emotion regulation, neurobiology (sMRI and fMRI), and contextual and experiential factors. This supplement will add measures that strongly and consistently predict substance use generally but have yet to be applied to the study of polysubstance use. In addition to the complement of measures in the Parent Study, this Supplement proposes to add measures of salivary stress responsivity and DNA to for a more comprehensive assessment of the precursors and consequences of polysubstance use. Our baseline sample includes substance-naïve preadolescents overselected for high risk of adolescent drug abuse. Our drug use survey will be expanded for the second wave of data collection (to begin December 2013) to assess patterns of polysubstance use if this supplement is funded. Given the paucity of research on polysubstance use other than studies that focus primarily on prevalence, preclinical models, adults and acute effects (with a few exceptions), there is a dire need to better understand the emergence and effects of polysubstance use. It is widespread, may involve particular risk factors over and above those associated with single drug use, and may exert greater damage.


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