A new study has uncovered why stimulant medications like Ritalin don’t help everyone with attention deficit hyperactivity disorder (ADHD).
While nearly 16 million adults in the U.S. have been diagnosed with ADHD, more than 30% don’t respond well to common treatments like Ritalin and Adderall.
The reason, researchers now say, may lie in how individual brains are wired—especially in the balance of certain brain chemical receptors.
The study, co-led by the University of Maryland School of Medicine and conducted at the National Institutes of Health (NIH), looked at how differences in dopamine receptors in the brain affect a person’s response to Ritalin.
Dopamine is a brain chemical that plays a key role in focus, memory, and attention.
The results were published in the Proceedings of the National Academy of Sciences.
To explore this, researchers studied 37 healthy adults without ADHD. They gave participants memory and concentration tasks and used brain scans to measure activity during these tasks—once after taking a placebo and again after taking Ritalin.
Another set of scans was used to measure dopamine levels and the presence of two types of dopamine receptors: D1 and D2.
At first, scientists expected that how much dopamine was released would predict how well someone focused on Ritalin. But they found something different. The real predictor of performance was the balance between the two types of receptors.
Participants with a higher ratio of D1 to D2 receptors generally had better memory and concentration from the start but didn’t show much improvement after taking Ritalin. Meanwhile, those with more D2 receptors compared to D1 had poorer memory at baseline but improved significantly when given the drug.
Dr. Peter Manza, lead researcher from the University of Maryland, said the findings show that it’s not just the amount of dopamine that matters—but how the brain’s receptors respond to it. Dr. Nora Volkow from the NIH added that the way D1 and D2 receptors interact plays a big role in how well Ritalin works for someone.
The study also has important implications for people who take stimulant drugs without a prescription. Many students and professionals use medications like Ritalin to try to boost performance, but this study suggests that if their brain chemistry isn’t right for the drug, it might not help them at all—and could even do harm.
Next, the researchers want to study people with ADHD to see if their D1/D2 receptor balance affects how well they respond to treatment. This could help doctors tailor treatments and offer better alternatives for those who don’t benefit from stimulant medications.
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