New research shows that chemical wiring in our brains has dramatically improved the focus of meths like Ritalin, while others are looking at findings that can change treatment approaches for millions of people with attentional disorders.
Clinical trials Proceedings of the National Academy of Sciences (PNA) and the University of Maryland School of Medicine (UMSOM) and the National Institutes of Health (NIH) have found that individual differences in brain chemistry, particularly the balance of specific dopamine receptors, play an important role in determining who will best respond to stimulants.
“We thought the amount of dopamine ritalin produced by a person would help predict whether an individual would improve attentional performance, but what we found is more complicated,” said Dr. Peter Manza, a PhD assistant professor of psychiatry at UMSOM. “Instead, the types of dopamine receptors on brain cells and the proportions they were found to find better predicted cognitive performance.”
The findings may help explain why almost a third of the 16 million American adults diagnosed with attention deficit hyperactivity disorder (ADHD) do not respond well to stimulants such as ritalin (methylphenidate) and Adderall.
Using advanced brain scanning techniques, the researchers looked at 37 healthy adults without ADHD who performed concentration and memory tasks after taking ritalin or placebo on different days. They measured both brain activity during these tasks and levels of two types of dopamine receptors (D1 and D2) that help regulate focus and attention.
Surprisingly, those with a higher ratio of D1 to D2 brain dopamine receptors performed better in memory tasks during baseline tests compared to those with more D2 receptors compared to D1 receptors. However, the opposition was true when it came to improvements from Ritalin.
“Balanced signaling between D1 and brain D2 receptors is required for optimal brain function and relative signaling variation. It contributes both to differences in baseline cognitive performance and why others may worsen performance when given Ritalin.”
This study showed that participants with higher levels of D1 receptors compared to D2 receptors tended to have improved baseline memory performance, but increased dopamine levels did not experience any significant improvement in ritalin. In contrast, patients with relatively large D2 receptors showed significant improvements when taking the medication.
These findings have implications beyond clinical treatment for ADHD. Researchers noted that there is growing concern about using meth without medical supervision to improve cognitive performance. This is known as the use of “cognitive enhancement” or “smart drugs.”
“A significant number of people without ADHD take stimulants in ways that are not predicted to improve performance. It was important to understand what these drugs are doing to the brain.” “Our findings suggest that many of these people may not benefit from taking these medications while taking the risk of using stimulants without medical supervision.”
The team is currently planning to extend the study to people clinically diagnosed with ADHD to look at the D1/D2 receptor ratio and determine whether people who respond poorly to drug therapy tend to have higher levels of D1 receptors.
“It will be interesting to identify whether there are subgroups of individuals with ADHD with high levels of D1 receptors and determine whether they are likely to withstand treatments with stimulants like Ritalin,” said Mark T. Gladwin, MD, dean of the University of Maryland School of Medicine. “It could help in efforts to personalize the care of these individuals and seek more beneficial treatments, including cognitive behavioral therapy.”
This finding adds to the growing evidence that individuality medicine coordinates treatments based on individuals’ unique brain chemistry – but can significantly improve the outcomes of neuropsychiatric symptoms that have traditionally been following all treatment models.
By uncovering the neurobiological mechanisms that determine who is best for meth, this study opens the door to more accurate diagnostic tools and more effective and personalized therapeutic strategies for millions with attentional disorders.
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