Announced by U.S. Secretary of Energy Bill Richardson
at a press conference on 9/29/98
National Institute on Drug Abuse press release
Brain scans showing Ritalin's effects
For more information, please contact:
Kara Villamil, 516-344-5658, or Mona S. Rowe, 516-344-5056
UPTON, NY - New research on Ritalin, a drug prescribed to millions of American children with Attention Deficit Hyperactivity Disorder (ADHD), indicates that it is safe if taken in pill form for that therapeutic purpose.
That finding will be reported in the October issue of the American Journal of Psychiatry by scientists from the U.S. Department of Energy's Brookhaven National Laboratory and the State University of New York at Stony Brook.
"This is reassuring news for the families who are struggling to deal with the genuine behavioral problems that attention deficit hyperactivity disorder presents," said Secretary of Energy Bill Richardson. "I applaud the research team for their insight and perseverance in making this beneficial discovery."
"It is extremely important to clarify that different methods of taking a medication can alter its medicinal effects and can make it more or less dangerous in ways totally unrelated to its clinical indications," said Dr. Alan I. Leshner, director of the National Institute on Drug Abuse, which jointly funded the research along with the Department of Energy. "This research helps explain why Ritalin rarely leads to abuse and addiction when taken properly as a treatment for ADHD."
The Brookhaven/Stony Brook researchers were concerned by reports of Ritalin abuse, aware that thousands of teens and adults snort it and inject it in order to get "high." The researchers showed that Ritalin is safe in therapeutic doses and that its effects are not sufficient to make children feel "high" or put them at risk of becoming addicted.
The research team made the first measurements ever of how the oral form of Ritalin, known chemically as methylphenidate, affects the human brain dopamine system, which is involved in the reinforcing and addictive effects of abused drugs. Using sophisticated brain imaging equipment and doses of Ritalin like those given to children, the scientists examined the brains of seven healthy young-adult volunteers and compared the results with those they had previously found for cocaine in cocaine abusers.
"This finding points out why Ritalin eases the symptoms of ADHD, without putting children at risk," said psychiatrist Nora Volkow, head of the research team and of Brookhaven's Medical Department.
"We saw a dramatic difference between Ritalin taken orally by ADHD children and Ritalin injected by teenagers and adults to get high, as well as the difference from cocaine," she continued. "And when the pathway to the brain is less direct, as with a pill, the effects aren't sudden enough to cause a high and to develop a reinforcing effect that leads to addiction. But they are enough to focus the attention of the child and calm the hyperactivity."
Volkow and her colleagues have studied Ritalin before, showing that, like cocaine, it raises levels of a brain chemical, or neurotransmitter, called dopamine. Their studies have focused mainly on injected Ritalin, confirming through science what high-seeking teens and adults already know through word-of-mouth: a snort or needle full of Ritalin can get you high.
But this latest study was the first to look at the therapeutic form taken by more than 2 million children with attention deficit hyperactivity disorder, the most common childhood behavioral disorder.
Brain cells release dopamine in order to send various signals inducing those of pleasure or reward for a person's behavior. Normally, dopamine molecules are released by one brain cell, travel through a gap between cells known as a synapse, and dock on a neighboring cell in order to send their pleasure signal. Then, the molecules travel back through the synapse to their "home" cells, which they re-enter through a gate known as a dopamine transporter.
When cocaine or Ritalin molecules enter the brain, though, they promptly take up residence on dopamine-producing cells, blocking the dopamine transporter "gates" and preventing dopamine from returning home. As dopamine builds up in the synapse, the signal to the neighbor cell is sent repeatedly. This effect is thought to be largely responsible for the "high" feeling experienced by drug users.
Brookhaven scientists have shown that in order for cocaine or injected Ritalin to make a person feel high, more than 60 percent of the brain's dopamine transporters must be blocked.
Until the current study, however, no exact measurement had been made of what percentage of transporters are blocked by oral Ritalin, or of the effect of typical oral doses on a person's feeling of "high" and other physical indicators.
In order to get that information, the Brookhaven/Stony Brook team examined the seven young adults at Brookhaven's Center for Imaging and Neurosciences, using a technique called positron emission tomography, or PET. The volunteers were each given a dose of Ritalin, calculated using their body weight to correspond to the doses given to children with ADHD. While the volunteers' brains were scanned in order to see how many dopamine transporters were blocked, they were asked to rate their feeling of restlessness and high. Meanwhile, physicians monitored their blood pressure and heart rate.
The results showed that only one of the volunteers reported feeling only slightly high, and several said they were slightly restless. More importantly to understanding why Ritalin is not addictive, Volkow said, was the fact that it took an hour on average to reach the peak in Ritalin's blockade of dopamine transporters. This is in marked contrast to intravenous Ritalin, for which peaks are reached within eight minutes, and for cocaine, whose effects peak within five minutes after administration.
Because ADHD is a complex syndrome, the researchers recognize that there may be other chemical reactions going on that are not detected by PET. But their results are striking, nevertheless.
Said Volkow, "The slow-acting effect we've seen with PET gives us confidence that the low oral doses given to children with ADHD cannot cause the quick and intense feeling of reward that is necessary to reinforce the behavior of taking the drug." This may also explain why medications such as the typically very addicting narcotic analgesics, when given orally, do not cause a high when used therapeutically
The study's authors also included Gene-Jack Wang, John Gatley and Naomi Pappas of BNL's Medical Department; Joanna Fowler, Jean Logan and Yu-Shin Ding of the BNL Chemistry Department; and Robert Hitzemann of SUNY Stony Brook's Department of Psychiatry.
The research was funded by DOE's Office of Energy Research and by the National Institute on Drug Abuse, part of the National Institutes of Health.
The U.S. Department of Energy's Brookhaven National Laboratory creates and operates major facilities available to university, industrial and government personnel for basic and applied research in the physical, biomedical and environmental sciences, and in selected energy technologies. The Laboratory is operated by Brookhaven Science Associates, a not-for-profit research management company, under contract with the U.S. Department of Energy.
These three sets of brain scans from a young adult given
a placebo (top) and two different doses of methylphenidate, or
Ritalin (bottom), show the ability of Ritalin to block the
transporter "gates" by which the brain chemical dopamine
returns to its home cell after sending a pleasure signal.
Red indicates more dopamine transporters available;
blue is least transporters available.