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."