SCIENTISTS MAY USE DRUGS TO STOP ADDICTION

NEW YORK - Can Prozac help you kick cocaine? Can Ritalin? How about a blood
pressure pill or medicine for muscle spasms? If you're an alcoholic, could
you get help staying sober by taking an anti-nausea drug used by cancer
patients?

Scientists are exploring those questions right now. In fact, in the field
of addiction medicine, one of the hottest sources of new drugs is ... old
drugs. Despite years of research, there is no drug approved in the United
States for treating cocaine dependence. To find such a treatment, the
National Institute on Drug Abuse is sponsoring human studies of 21
medicines already on the market for something else. That's about two-thirds
of all the potential cocaine drugs being tested in people, says Frank
Vocci, director of NIDA's pharmacotherapy division.

Over at the National Institute on Alcohol Abuse and Alcoholism, nearly all
the potential alcoholism drugs tested in people under institute sponsorship
over the past 10 years were previously approved for some other use, says
Raye Litten, co-leader of the institute's medications development team.

While the strategy is hardly new, "it's been going on maybe just a bit
below the radar screen" for most of the public, Vocci said.

It can certainly work. In 1997, for example, the government approved a
stop-smoking pill called Zyban, which was in fact the older antidepressant
Wellbutrin.

To be sure, experts haven't given up on developing new drugs. Most
NIAAA-funded drug studies for alcoholism that are in early stage testing -
not yet tried on people - are brand-new drugs, Litten said.

But the notion of examining current drugs for addiction-breaking potential
holds several advantages. It's a lot cheaper to get federal approval for a
new use of an old drug than to bring a completely new medicine to market.
And experience with an existing drug gives an idea of its safety and dose
range for possible anti-addiction effects, Vocci said.

He and others caution that people who happen to have medications on hand
that show promise in such studies shouldn't give them to friends and family
with addiction problems. That must be left to professionals. Experts also
say that even effective anti-addiction medicines usually can't work by
themselves, but must be used along with non-drug therapy.

The most straightforward approach to testing an existing drug is to follow
its approved purpose, but in a different way. For example, some scientists
are studying how to prolong the effects of naltrexone, now usually given as
a daily pill for treating dependence on alcohol or opiates like heroin and
morphine.

Dr. David Gastfriend of Massachusetts General Hospital and Harvard Medical
School and other researchers recently reported that specially formulated
naltrexone helped alcoholic men cut down on their drinking for a month when
they received the drug as a shot in the buttocks.

Why is a monthly visit to a doctor better than just taking a pill every day?

"The pill requires a daily awareness that this is a dangerous disease and a
rational decision to take the pill," Gastfriend said. "The problem with
this illness is that on any given day, a person can feel, 'No, it would be
better if I could drink.' So you take the pill the first day and you have
to make 29 more decisions" the rest of the month.

"But if you received an injection the first day, those 29 decisions have
already been made," said Gastfriend, a paid consultant to Alkermes Inc.,
which is developing the formulation he studied, called Vivitrex.

More striking than just reformulating a drug is finding a new and
apparently unrelated use for it. Here, scientists are guided by emerging
knowledge about how addiction hijacks the brain.

Addicts apparently suffer from a combination of unusually strong desire for
a drug and a weak inhibition against using it, Vocci said.

"These people essentially have a revved-up engine and thin brake pads," he
said.

In the brain, scientists have found that cocaine produces euphoria by
stimulating nerve circuits that communicate with a substance called
dopamine. So they've looked for medications that can affect the activity of
this dopamine system.

One is a decades-old old drug called baclofen (pronounced BAK-loe-fen),
used to treat spasms, cramps and muscle tightness in people with multiple
sclerosis or spinal problems. Steven Shoptaw, a researcher at the
University of California, Los Angeles, recently published a preliminary,
federally funded study that suggested it can cut cocaine use in addicts. A
much larger study is now under way to confirm that, but for now the drug
looks promising, Shoptaw said.

Other drugs that work in a similar way and that are being tested in cocaine
addicts include the anti-seizure medications tiagabine, topiramate and a
drug sold overseas as Vigabatrin.

Cocaine withdrawal symptoms might be eased by boosting the brain's depleted
dopamine levels. So scientists are studying dopamine-boosting drugs like
Ritalin, used for attention deficit hyperactivity disorder, and amantadine,
used for flu and Parkinson's disease.

But addiction is complicated enough to involve many brain circuits, which
in turn provide many targets for anti-addiction drugs. Inderal, a
blood-pressure medicine, may reduce cocaine craving during early abstinence
by interfering with the actions of another brain substance, norepinephrine.
The antidepressants Prozac and Effexor, which boost levels of yet another
brain chemical called serotonin, are also under study in cocaine dependence.

Then there's ondansetron (pronounced on-DAN-se-tron), which is normally
used to prevent nausea and vomiting after cancer chemotherapy or surgery.
Scientists are studying it for both cocaine and alcohol abuse, again for
its action in the serotonin circuitry.

It might seem logical that a single drug could help in multiple kinds of
addiction, but even that situation can come with a twist. Consider
Antabuse, the anti-alcohol drug that works by making users sick if they
drink alcohol. Scientists recently found, unexpectedly, that Antabuse also
helps cocaine-dependent people cut back on cocaine, though not by making
them sick.

Just how it does that isn't clear, says researcher Dr. Thomas Kosten of
Yale University. Antabuse hampers the normal breakdown of cocaine by the
body, and boosts dopamine levels while reducing norepinephrine levels, he
said. The net effect may be to reduce both withdrawal symptoms and desire
to seek cocaine, he said.

Shoptaw thinks that within the next five years, some drug will win approval
for treating cocaine dependence. Baclofen, topiramate and Antabuse lead his
list of candidates. Each may find a use in a different phase of cocaine
dependence, such as getting off the drug or staying off, he said.

And addiction specialists are eagerly looking beyond today's medicine
cabinet toward a drug that isn't approved for anything in the United States
yet. Rimonabant blazed into the headlines in March when researchers
reported evidence that it might help people battle both cigarette smoking
and obesity.

But why stop there?

Rimonabant blocks the brain's docking sites for its own marijuana-like
substances, part of the "cannabinoid" system that might play a role in
addictions beyond food and nicotine, says Dr. Herbert Kleber of Columbia
University.

Once the drug is approved for either smoking or obesity, he expects
researchers will jump in and test it for things like heroin and cocaine.

And the strategy of squeezing new uses of out existing drugs may score
another success.