Study Description - CRAN Neurodevelopment Initiative

National Longitudinal Study of Neurodevelopmental Consequences of Substance Use

(Final Title and Acronym TBD)

Problem Statement:  Research suggests that drugs (including nicotine and alcohol) affect the developing brain in lasting ways.  However, no prospective study has been conducted to definitively assess the effects of drug exposure on human brain development. 

Rationale:  As policy over drugs in the U.S. continues to be debated, there is a growing chance that our youth will have greater access to drugs, particularly marijuana.  Within this context there is an urgency to understand the effects of marijuana, alcohol, nicotine, and other drugs to the developing human brain.

Background:  Advances in brain imaging technologies have provided new tools with which to investigate human brain development.  For example, with brain imaging it is now possible to measure the effects of substance use on brain architecture and function and link these to cognitive and emotional behaviors. Substantial evidence from animal models studies has shown that drug use is particularly deleterious during the adolescence period, which brain imaging allows us to now study in humans.

Study Aims:  This study intends to answer the following major questions:

  1. What is the impact of the occasional  versus  regular use of marijuana, alcohol, nicotine and other substances on the developing brain?  In what ways does use of one substance predispose toward or interact with use of others (gateway interactions)?
  2. What are the neurodevelopmental pathways that link adolescent substance use and pre-existing or emerging mental illnesses? What are the effects of multiple substances in combination? 
  3. What impact do these substances have on information processing, academic achievement, motivation, social development, and other behaviors?

Partnering Agencies: The study will be led by the Collaborative Research on Addiction (CRAN) at NIH (National Institute on Drug Abuse [NIDA], National Institute on Alcohol Abuse and Alcoholism [NIAAA], and the National Cancer Institute [NCI]) in collaboration with the National Institute of Child Health and Human Development (NICHD) and potentially other Institutes including the National Institute of Mental Health (NIMH).

Study Design:  The study will consist of a large representative cohort (i.e. approximately 10,000) youth that will be followed over a 10-year period, beginning before drug use is initiated and continuing into early adulthood. It is essential that the study begins before adolescence and prior to drug use, and that its sufficiently powered so as to be able to address the effects of different levels of drug exposure on the developing brain. Imaging technology, neuropsychological testing, and psychiatric evaluation will be used to document changes in adolescent brain function over the span of the study.  Outcome measures will include substance use, academic achievement, IQ, and cognitive skills.

Focus of the Meeting: Study Design

  1. Sample size/population sampling:
    1. Is 10,000 sufficient to provide the level of discernment needed to answer the study questions?
    2. Should oversampling be done on high-risk participants; racial/ethnic groups; specific localities (e.g., Colorado, Washington)?
    3. How many sites are needed to recruit a sample of this size?
    4. How do we maximize recruitment and ensure retention (especially in a highly mobile population)
  2. Duration of study/Intervals for follow up:
    1. Ten year period is planned beginning before drug use is initiated and continuing into early adulthood (~ages 11-21).
    2. Is that the right age group?
    3. How often should follow up occur for neuroimaging? Other outcome measures?
  3. Imaging:
    1. What types of imaging should be used?
    2. How do we harmonize methods of collection; data entry, etc – is there a need for a data coordinating center?
  4. Measures of drug use:
    1. What measures do we need to get a well characterized sample, including frequency of use/route of administration (e.g. electronic delivery devices, cannabis edibles)/co-administration of substances/medical mj, and full range of substances.
    2. Are there validated survey questions that can be used for each?
    3. How often should these be measured?
    4. How should the questions change as the cohort ages?
  5. Co-morbidities/other characteristics likely to affect or predict risk for SUD and other psychiatric disorders:
    1. Childhood psychiatric disorders or symptoms (e.g., ADHD, anxiety, conduct disorders), and psychotherapeutic medications/psychotherapy
    2. Trauma exposure (emotional and physical—head trauma)
    3. Affective States/Emotional Regulation
    4. Family functioning/loss
    5. SES, other contextual variables that could effect data interpretation
  6. Outcomes
    1. Neurocognitive function
    2. Social Development
    3. Mental disorders
    4. Substance Use Disorders
    5. Academic achievement/IQ
    6. Physical health—BMI, asthma, etc.
    7. Drug use during pregnancy (as the cohort ages)
    8. Genetic findings; G X E interactions
    9. Biomarkers of substance use
  7. Ethical issues
    1. Confidentiality vs. informing parents of substance use
    2. Management of incidental and medically actionable findings
    3. Consent issues
    4. Parental Involvement
  8. Costs of the study
  9. Data Sharing requirements