Pubdate: Sat, 18 Apr 1998 Source: New Scientist Contact: http://www.newscientist.com/ Author: Alison Motluk CALM BEFORE THE STORM This autumn, the US National Institutes of Health will host a conference that will focus on a drug regularly taken by millions of American children. It is in crucial ways similar to cocaine, and some experts fear it could encourage substance abuse in later life. But this is not the latest street drug--it is prescribed by doctors. Methylphenidate, better known as Ritalin, is the leading treatment for a neurological condition known as attention deficit-hyperactivity disorder (ADHD), which prevents children--mostly boys--from focusing their mental energies. Sufferers find it impossible to concentrate on a task for more than a few seconds, constantly move around and are impulsive and jittery. Scientists have little idea what causes the disorder, although they believe it involves the failure of certain receptors in the brain to respond to the neurotransmitter dopamine. Ritalin has transformed the lives of ADHD children. It has become by far the most popular drug for dealing with the condition, with a 90 per cent share of the market. According to the US Drug Enforcement Agency (DEA), production of Ritalin in the US increased almost fivefold in the five years to 1995. RAPID RISE Ritalin has been around for more than forty years, and was originally used to treat the sleeping illness narcolepsy. Its increased use is mainly due to the rapid rise in the number of people diagnosed with ADHD, especially in the US. Some doctors claim that up to 5 per cent of all boys and 2 per cent of girls worldwide--and a large number of adults--suffer from the condition. Outside the US, doctors are more sceptical about ADHD, but even those who believe Ritalin is being overprescribed agree that it is a genuine disorder and that Ritalin really does help. But over the past few years there have been growing fears about its long-term effects. Ritalin is a stimulant that works by making dopamine more available in the brain. Its effects in the brain are very similar to cocaine, and some researchers are warning that regularly giving children a cocaine-like substance might prime them for drug abuse later in life. They also say that children on Ritalin are more likely to smoke. Fears such as these have put Ritalin firmly on the agenda for the National Institutes of Health conference on ADHD, scheduled for November. Concerns about Ritalin began to emerge in 1995, with a study in the Archives of General Psychiatry entitled "Is methylphenidate like cocaine?". The paper concluded that it was. Its lead author, Nora Volkow, director of nuclear medicine at the Brookhaven National Laboratory in Upton, New York, used positron emission tomography (PET) scans to look at where and how quickly Ritalin acts in the human brain. In Volkow's study, eight healthy male volunteers were injected with the drug. Their scans were then compared with those of subjects in previous studies who had been injected with cocaine. The authors reported that the distribution of Ritalin in the human brain was "almost identical to that of cocaine". The drugs' effects also peaked at almost the same time--between 4 and 10 minutes in the case of Ritalin, and 2 to 8 minutes for cocaine. Even the highs were similar. "We've given it to cocaine users and they say it's almost indistinguishable," says Volkow. The only significant difference was that Ritalin took over four times as long--90 minutes--to leave the body. "We're dealing with a drug that does have properties very similar to cocaine." This is obviously worrying. "Cocaine is one of the most addictive substances of abuse," says Volkow. "Ritalin we give to children." She stresses, however, that taking a stimulant orally is very different to injecting or snorting it. Intravenous caffeine also resembles cocaine, she points out. Her paper warned that similarities between cocaine and Ritalin "should not be used as an argument against the use of methylphenidate". And she admits that there is no evidence of a link between Ritalin use and cocaine abuse. But she adds: "We do have evidence that if we don't treat them, then they will turn to self-medication." She says that 10 to 30 per cent of cocaine abusers take cocaine because they have ADHD. "When we give them Ritalin, the cocaine problem is resolved." Volkow's results came on top of earlier animal experiments suggesting that prolonged exposure to some stimulants made rats more likely to become addicted to cocaine. One such study by Susan Schenk, a psychopharmacologist at Texas A&M University in College Station, involved rats that pressed a lever to give themselves cocaine. The experiment showed that rats given amphetamines for nine consecutive days were more likely to give themselves cocaine than rats that had been given saline solution. The fear is that, like amphetamines, Ritalin primes the brain so that any later use of cocaine has a bigger effect than it would otherwise. If so, Ritalin may make people more likely to abuse cocaine or other stimulants, rather than experiment with them once or twice. To find out whether her findings had implications for children taking Ritalin, Schenk teamed up with Nadine Lambert, a developmental psychologist at the University of California at Berkeley. Lambert followed the progress of 5000 children with ADHD in the San Francisco area from adolescence into adulthood to discover whether the drug has any effect on tobacco, alcohol and illicit drug use in later life. In a paper to be published in October in the Journal of Learning Disabilities, Lambert claims that children who take Ritalin are more likely to smoke as adults. Other data, which Schenk presented at a meeting held by the DEA in December 1996 and are being revised for publication, suggest that they are no more likely to abuse alcohol or marijuana, but are three times more likely to develop a taste for cocaine. Not everyone is convinced. Alan Zametkin, a psychiatrist at the National Institute of Mental Health near Washington DC, says that the team's research design was flawed because their subjects were not assigned at random. Those sufferers on medication were probably more severe cases than those who were not, he says. Schenk admits that there are uncertainties in the team's study, but points out that whether or not the children were treated had little to do with the severity of their condition. For instance, those not on medication may have had parents who were against the use of drugs such as Ritalin. Another attempt to monitor children taking Ritalin into early adulthood supports Zametkin's scepticism. Lily Hechtman, a psychiatrist at the Montreal Children's Hospital, looked at people who had taken Ritalin for three to five years, and compared them with people who were not hyperactive and people who had been diagnosed with ADHD but not given the drug. She found no significant differences in patterns of substance abuse among the three groups. Zametkin goes further. He believes that sufferers who are given Ritalin are less--not more--likely to abuse drugs later in life. "My theory is that stimulant use allows kids to be more successful and therefore they develop fewer antisocial behaviours," he says. "So it's less likely they'll become drug addicts." Schenk, too, accepts that Ritalin is a useful drug. In a cost-benefit analysis, she says, any side effects would probably pale in comparison to the good it does. But that does not mean that you should not look for them, she says. "You still have to know what the costs are."