Pubdate: Mon, 30 Aug 2004
Source: Lexington Herald-Leader (KY)
Copyright: 2004 Lexington Herald-Leader
Contact:  http://www.kentucky.com/mld/heraldleader/
Details: http://www.mapinc.org/media/240
Author: Malcolm Ritter, Associated Press
Bookmark: http://www.mapinc.org/pot.htm (Cannabis)
Bookmark: http://www.mapinc.org/coke.htm (Cocaine)
Bookmark: http://www.mapinc.org/heroin.htm (Heroin)

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.
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MAP posted-by: Jo-D