# Brain Indices of Stimulant Treatment in Drug-Naive Youth at Risk for Substance Use Disorder

> **NIH NIH R21** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $211,875

## Abstract

Children with attention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder (ODD) and conduct
disorder (CD) are known to have elevated risk for adolescent-onset substance use disorders (SUD), and those
with comorbid ADHD + ODD/CD are at greatest risk. Stimulant medications such as extended release mixed
amphetamine salts (MAS–XR) and non-stimulant medications (e.g. atomoxetine or guanfacine) have
established efficacy for ADHD and are also beneficial for ODD/CD. However, stimulants have direct effects on
the brain reward system, and abnormal reward processing is thought to mediate addiction vulnerability.
Although longitudinal studies have not shown increased SUD risk in youth with ADHD treated with stimulants, it
remains unknown whether stimulants might have differential effects on reward processing in high risk (HR) vs.
low risk (LR) populations.
fMRI offers a cost effective method of evaluating covert effects of stimulant medications for youth with ADHD
and SUD risk by examining pre- to post-treatment changes in activation in the brain reward system that
predate exposure to drugs of abuse. This approach is supported by the results of studies, which indicate
altered (mostly elevated) sensitivity in the reward system in youth at-risk for SUD; high activation in the reward
system has in turn been linked to problem drug use. However, to date, no study has examined changes in the
reward system with stimulant treatment in youth with ADHD and high vs. low risk for SUD, who have never
been exposed to stimulant treatment or drugs of abuse. Such research could provide important knowledge
regarding the biological basis of addiction vulnerability and guide treatment selection.
Our team is in an excellent position to study differences in activation in the brain reward system during fMRI
before and after treatment with MAS–XR in young children (8-12 years old) with ADHD, who are naïve to both
stimulant treatment and drugs of abuse, divided into LR (i.e., ADHD only) and HR (i.e., ADHD + ODD/CD)
groups. We will confirm that youth with ADHD/HR status have exaggerated activation in the reward network
compared to ADHD/LR youth and controls, and test competing hypotheses regarding the effects of the two
medications on the brain reward system, and across the different risk groups. This protocol is innovative in its
approach to study young, drug-naïve children at various levels of SUD risk, and is highly significant in its use
of neuroimaging to delineate possible differential effects of stimulant and non-stimulant medications on reward
processing in youth with ADHD and HR vs. LR for SUD as a biomarker of treatment-related risk. This research
will substantially advance our understanding of the biological basis of vulnerability for addiction, and aid in the
development of treatment recommendations for youth with ADHD and varying levels of SUD risk.

## Key facts

- **NIH application ID:** 9928405
- **Project number:** 5R21DA046029-02
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Iliyan Stoyanov Ivanov
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $211,875
- **Award type:** 5
- **Project period:** 2019-05-15 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9928405

## Citation

> US National Institutes of Health, RePORTER application 9928405, Brain Indices of Stimulant Treatment in Drug-Naive Youth at Risk for Substance Use Disorder (5R21DA046029-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/9928405. Licensed CC0.

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