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Ritalin, the immensely popular drug of choice for treating childhood Attention Deficit / Hyperactivity Disorder, is getting a nervous second look by medical groups and pediatricians due to potential long-term health effects -- a concern highlighted by the recent death of a 14-year-old Michigan boy that was reportedly caused by the drug.

Last week, the Asheville Tribune reported that Matthew Smith of Oakland County, Mich., collapsed March 14 in cardiac arrest while skateboarding. He was a victim of steady cardiovascular decay after a decade of Ritalin use, according to Dr. Ljubisa Dragovic, chief pathologist at the Oakland County medical examiner's office.

"There was a chronic change of the heart muscle and the small blood vessels in the heart," he said. "This comes from long-term exposure. This kid was on (Ritalin) repeatedly for 10 years." Dragovic said that after a thorough analysis he found the boy's small blood vessels manifesting scarring and tissue growth consistent with chronic stimulant use. And, he said, witnesses stated that Matthew had earlier complained of chest pains before he collapsed while playing on a skateboard. He also found that the drug affected pathways throughout the nervous system over time, causing "gradual, low-level" damage.

Ritalin triggers changes to the brain long after its so called calming effects have worn off, scientists report. Researchers say that questions remain about its long-term side effects. The changes, which are not fully understood, are similar to those occurring with other forms of amphetamine and also cocaine.

New evidence about the effects of Ritalin has prompted renewed calls for research into its long-term effects. Dr Joan Baizer and colleagues from the University at Buffalo, State University of New York have found that relatively high doses of the drug methylphenidate, the generic form of Ritalin, changed the expression of a gene involved in brain function in laboratory rats. The same gene is known to be affected in humans by other psychoactive drugs, such as amphetamines and cocaine.

DR Bazier and team noted that previous studies had shown high doses of amphetamines and cocaine changed certain aspects of brain cell function. Ritalin, like these drugs, is a stimulant, so they decided to test whether it might have similar effects.

Young rats were used in the experiment. One group was given sweetened milk containing Ritalin, and their brains were compared to those of another group given just sweetened milk.

According to DR Baizer, the dose used was comparable to the high end of the dose used to treat children who are thought to have ADD and ADHD, after taking into account differences in metabolism between rats and humans.

The researchers found Ritalin increased the activity of a gene called c-fos in the striatum, a part of the brain involved in movement and motivation.

"These data do suggest that there are effects of Ritalin on cell function that outlast the short term and we should sort that out," DR Baizer said.

ADHD researcher DR Alasdair Vance of Melbourne's Alfred Hospital said the study demonstrated the importance of studying the long-term effects of Ritalin.

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