Ritalin May Trigger Long-Term Brain Cell Changes

From the WebMD Archives

Nov. 12, 2001 -- Kids all over the country take Ritalin to relieve symptoms of attention deficit hyperactivity disorder (ADHD). But the drug may trigger brain changes that remain after the child quits taking the drug, according to a study being presented at this week's annual meeting of the Society for Neuroscience.

Doctors have always considered the drug to be short acting, meaning that once it worked its way through the child's system, it was gone. This new study involving mice shows changes similar to those that occur with other stimulant drugs.

But experts say the evidence is too preliminary to draw any conclusions -- or to take your child off Ritalin. "I don't see any clear evidence for long-lasting changes in brain function," says James McCracken, MD, director of child and adolescent psychiatry at UCLA, after reviewing the study for WebMD.

Researchers have long known that Ritalin acts in the brain much like cocaine and amphetamines, says study author Ashley Acheson, a researcher in psychology at the University of Buffalo. "It's the same basic pattern." However, they have not thought there were any lasting effects after the drug is out of a child or adult's system.

In his study, he gave one group of young rats sweetened milk containing a relatively high dose of Ritalin. The dose and time of day of the rats' treatment was comparable to a child's dosing schedule. The other group was given plain sweetened milk. After 90 minutes, researchers analyzed the rats' brains.

Acheson found that certain brain cell genes called 'immediate early genes' were switched on, and that action caused changes in some aspects of nerve cell function. Amphetamines and cocaine both cause similar gene changes in areas of the brain that control movement and motivation.

However, his findings "don't mean this drug is bad," Acheson tells WebMD. "When [Ritalin] is prescribed, it's seems to be very safe, with low potential for abuse. All indications are that when it's used as prescribed, it's a very safe and effective drug."

However, the study does suggest the drug "may have some effects that last longer than the therapeutic actions," says Acheson. "We really don't know what those are, and by no means do we know if those changes are bad."


But McCracken tells WebMD that 90 minutes is not enough time to say that Ritalin has long-lasting effects on the brain.

The next study will investigate the effects of long-term Ritalin treatment, a more realistic scenario than this study's one high-dose treatment, he says.

Nora Volkow, MD, head of the biology and medical departments at New York's Brookhaven National Laboratory, part of the U.S. Department of Energy, also agreed to review Acheson's study for WebMD. She has done much research with high-tech imaging, peering into the human brain to see how Ritalin works.

"This study is telling us something we cannot ignore," she tells WebMD. "[Ritalin's] therapeutic effects may in fact require activation of a sequence that can produce addiction, but when properly activated can enhance performance and can improve function in a child with ADHD."

However, the rats used in Acheson's study are normal rats -- they don't have ADHD symptoms, she points out. "We cannot predict that the same responses would happen in animals that have the same [symptoms] as an ADHD child, right?"

Further research is needed to determine how all this applies to humans, Volkow says. "I would like to see how long-lasting the changes are, how they affect the brain's function. Will they make that region [of the brain] more active, less active, or more responsive? What is the significance? How does that play out in terms of behavior?"

McCracken has trouble with the "massively high dose of drug used in the study -- fully 10 to 20 times what's used in clinical practice," he says. How realistic can the results be?

"Even though Ritalin is similar to cocaine and amphetamine, the subtlety of differences in its [formula] make it safe and clinically effective for ADHD," McCracken tells WebMD.

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