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2016-2020 NIDA Strategic Plan

Objective 1.2: Identify the factors that influence drug use trajectories

SUDs are complex conditions that develop over time and are characterized by stages of initiation, escalation, problematic use, and addiction, the latter often being associated with cycles of withdrawal and relapse. However, not all individuals who initiate drug use progress to addiction; some discontinue use quickly, and others maintain a low level of use without escalating to problematic use or addiction. Also, some individuals who develop problem use or addiction are able to stop without formal treatment, whereas others are treatment-resistant.48, 49

Genetic epidemiology suggests that individual trajectories are influenced by the environment, the age of initiation, and genetic vulnerabilities. Initiation and dependence share some common genetic factors, but unique genetic factors also underlie the different stages of substance use, as well as individual vulnerability for addiction to particular substances.50

The heterogeneity of substance use phenotypes and individual genetic variation present significant challenges for understanding the genetic and environmental factors that mediate the development of SUDs. Identifying and characterizing biologically relevant behavioral phenotypes will enhance the probability of identifying risk genes, relevant environmental and social risk and protective factors, development factors associated with SUD behavior, and, ultimately, objective diagnostic biomarkers.


  • Conduct longitudinal studies to examine the impact of drug use on development
  • Improve standardization and depth of phenotypic and environmental characterization
  • Support efforts to develop large data sets, integrating data across many scientific disciplines and data types to support more comprehensive characterization across stages of the SUD trajectory

A Look Inside the Teen Brain: the Adolescent Brain Cognitive Development (ABCD) Study

Decades of neuroscience research has shown that adolescence is a period of significant brain development and that experiences during this time can have a profound impact. For this reason, it is a crucial window during which a wide range of biological and environmental factors and health behaviors can influence and shape a person’s cognitive development and associated life outcomes in both positive and negative ways. Experiences such as physical activity and sleep; stress; injuries from sports and other activities; substance use; mental illness; and socioeconomic, genetic, and developmental factors shape the developing brain. But because of their variety and complexity, our understanding of precisely how these experiences interact to affect brain development and social, behavioral, and health outcomes is still incomplete. To address this gap, we need to study a large and diverse group of children, starting early in adolescence, and follow them throughout the window of developmental vulnerability.

To this end, NIDA is leading a collaborative effort in partnership with NIAAA; NCI; the Collaborative Research on Addiction at NIH, or CRAN; and other NIH partners (NICHD, NIMH, NIMHD, NINDS, and OBSSR) on a new Adolescent Brain Cognitive Development (ABCD) study. This study is the largest-ever longitudinal brain imaging study of adolescents. ABCD will recruit 10,000 youth at age 9 or 10 and follow them over 10 years, into early adulthood, to determine how a wide range of behavioral, genetic, and environmental factors interact and influence brain structure and function as well as life and health outcomes. Studies will track mental health, substance use patterns, academic achievement, IQ, cognitive skills, and many other outcomes. The longitudinal design of the study will allow us to draw more meaningful conclusions and connections at the individual level, between key genetic and biological, behavioral, social, and environmental factors during adolescence.

Importantly, the size and scope of the ABCD study will allow scientists to answer pressing questions about the effects of biology, environment, and experience on the developing brain and the risks for specific health outcomes including substance use and other mental disorders. Also, the inclusion of roughly 800 twin pairs will yield invaluable data about the role of genetic versus environmental factors in development. The large data set will also allow scientists to answer pressing questions about the impact of substance use on physical health, psychological development, learning and memory, academic achievement, and other outcomes.

By leveraging recent advances in technology, this landmark study will help transform our understanding of genetic and environmental influences on brain development, structure, and function and also identify potential predictors of teen drug use. This information can then be used to improve our ability to predict, mitigate, or counteract the risk of substance use disorders among our nation’s youth through more effective prevention messages and treatment interventions.