Indianapolis, Indiana – Indiana University researchers have received a major boost in their efforts to understand the risks and benefits of attention-deficit/hyperactivity disorder (ADHD) treatment. Backed by a $3.7 million grant from the National Institutes of Health’s National Institute on Drug Abuse (NIDA), the team will lead one of the largest studies to date examining how ADHD medications may influence serious substance use problems among young people on Medicaid.
The study will focus on over 3.3 million children, teenagers, and young adults, ages 9 to 29, who have been diagnosed with ADHD. By analyzing this vast dataset, researchers hope to clarify whether treatment with stimulants and non-stimulant medications alters the risk of dangerous outcomes such as overdose, addiction, or long-term dependency. While millions of young people live with ADHD, their likelihood of developing major substance use problems varies, and current research has left families and clinicians with more questions than answers.
“Treatment of ADHD is very controversial, and the role of ADHD medication in substance use problems is a huge question in the field,” said principal investigator Brian D’Onofrio, the Sharon Stephens Brehm Endowed Professor in IU’s Department of Psychological and Brain Sciences. “Our research seeks to address the uncertainty, to help provide clear, evidence-based answers for the families and clinicians who struggle daily to weigh the benefits and risks of starting, stopping, or changing ADHD medication. What is unique or novel about our approach is that we are going to use a series of different designs to help us make better causal claims about ADHD medications among a vulnerable population that has not been studied extensively to date.”
Why This Study Matters
ADHD is one of the most common neurodevelopmental disorders, often diagnosed in childhood but persisting well into adolescence and adulthood. Although many young people with ADHD never encounter major substance-related issues, the disorder is associated with higher risks for both misuse of drugs and overdoses. At the same time, ADHD medications themselves—particularly stimulants like Adderall and Ritalin—carry their own stigmas and concerns about misuse, diversion, or unintended long-term effects.
Existing studies have fallen short for several reasons. Small clinical trials, while controlled, often lack the size necessary to capture rare but serious outcomes like fatal overdoses. Larger database analyses, meanwhile, have struggled with representativeness, as they did not always include youth from diverse racial, ethnic, and socioeconomic backgrounds. This new IU-led project addresses those gaps by leveraging Medicaid data—a system that covers a large and often underserved population.
The project will take advantage of advanced epidemiological tools to examine treatment patterns and their long-term consequences. Importantly, the dataset will also allow researchers to investigate disparities across communities. Preliminary evidence already suggests that Hispanic and Black patients have shorter treatment periods compared to their non-Hispanic White counterparts. Understanding why these differences exist, and what impact they have, is central to the team’s mission.
Questions Driving the Research
The project will tackle three pressing questions. First, who is receiving which medications, and how long do those treatments typically last? The team will map treatment patterns across demographic groups, taking into account age, co-existing conditions, and cultural or socioeconomic influences.
Second, does beginning medication actually lower the risk of severe outcomes? By comparing the rates of substance use problems before and after patients begin treatment, the team hopes to uncover whether stimulants or non-stimulants play a protective role, or whether they have little impact.
Third, what happens when long-term treatment is stopped? Many families face the decision of whether to continue medication for years at a time. This study will explore whether discontinuing treatment after extended use increases vulnerability to substance misuse compared to maintaining a medication regimen.
A Global Advisory Effort
To ensure the results can be translated into practical guidance, IU researchers will not work in isolation. An international advisory board of pediatricians, psychiatrists, clinical guideline developers, foster-care experts, and community advocates will provide insights alongside epidemiologists, data engineers, and clinical scientists. Their collective goal is to turn raw data into real-world solutions for families, physicians, and policymakers.
“Overall, we are trying to answer questions that are being very heavily debated right now. What is the role of different psychiatric medications in the treatment of children, adolescents, and young adults? And we’re able to do it in a way that is without any conflicts of interest and that is built on the expertise of a large group of people from clinicians to guideline developers,” D’Onofrio said.
Building on Institutional Support
This ambitious project rests on years of foundational work. D’Onofrio pointed to IU’s institutional support as essential in paving the way for a grant of this scale. “We have benefited greatly by resources provided by the University, the College of Arts and Sciences, and the Indiana Clinical Translational Science Institute,” he noted. “These institutions have made the current research possible.”
Equally important, he emphasized, is the independence of the study. “As a federally funded project, we are not beholden to or restricted by any means. We have no financial conflicts of interest with the pharmaceutical industry, for example.”
A Large Team with Global Reach
The research team spans several institutions across the United States and abroad, reflecting the scope and importance of the project. Co-investigators include Patrick Quinn of IU Bloomington, Tanya Froehlich and Sarah Beal of Cincinnati Children’s Hospital Medical Center, Zhang Chang of Karolinska Institutet in Sweden, Samuele Cortese of the University of Southampton in the United Kingdom, Julianne Giust of IU School of Medicine in Evansville, James Guevara of the Children’s Hospital of Philadelphia, Leslie Hulvershorn of IU School of Medicine in Indianapolis, Kelly Kamimura-Nishimura of Cincinnati Children’s Hospital, Henrik Larsson of Örebro University in Sweden, John McConnell of Oregon Health and Science University, Tennisha Riley of the University of Florida, and Timothy Wilens of Harvard Medical School.
Together, they represent a multidisciplinary alliance capable of addressing the many dimensions of ADHD treatment and its potential consequences.
Looking Ahead
The findings of this study could reshape the way doctors, parents, and policymakers approach ADHD treatment. By clarifying whether medications increase or decrease the risk of serious substance use problems, the project has the potential to reduce stigma, refine prescribing practices, and ensure that treatment plans are tailored more effectively for each individual.
For families weighing the risks and benefits of medication, the results may offer long-awaited clarity. For healthcare providers, the study may strengthen guidelines and lead to more equitable treatment across communities. And for policymakers, the evidence may inform laws and funding priorities that improve care for millions of vulnerable young people.
In the end, the IU team hopes their work will serve as both a scientific milestone and a practical resource. By shedding light on one of the most contested questions in child and adolescent psychiatry, the project may help guide decisions that could shape lives for decades to come.
