Pubdate: Fri,  5 Jul 2002
Source: Wall Street Journal (US)
Copyright: 2002 Dow Jones & Company, Inc.
Contact:  http://www.wsj.com/
Details: http://www.mapinc.org/media/487
Author: Gautam Naik, Staff Reporter Of The Wall Street Journal
Bookmark: http://www.mapinc.org/rehab.htm (Treatment)

DRUG MAKERS TEST VACCINES AND DRUGS TO HALT ADDICTION

Recently, about 50 smokers in Belgium were injected with an unusual drug 
code-named TA-NIC. After taking as many as five doses over 10 weeks, two 
smokers quit. Several others reported a lower desire to smoke, according to 
Xenova PLC, the drug's British maker.

The experimental drug is one of the first attempts to design an antismoking 
vaccine. By producing antibodies in the user's blood, it prevents nicotine 
molecules from entering the brain and triggering a "high." Denied such 
pleasure, a smoker theoretically has less incentive to light up.

Vaccines are just one of several new approaches to fighting the escalating 
problem of addiction. About 1.2 million people in Western Europe and 3.2 
million Americans are hooked on hard drugs such as heroin, cocaine and 
speed, according to the United Nations. Millions more are dependent on 
tobacco and alcohol. Dealing with this -- in terms of health care, law 
enforcement and lost productivity -- costs $300 billion (€306.18 billion) 
each year in the U.S. alone. No world-wide or European estimates are available.

So far, medical efforts to fight addiction have been disappointing. Relapse 
and dropout rates are high. Despite the huge revenue opportunity, big drug 
companies have barely gotten involved, largely because of the social 
stigma. Until recently, science has also struggled to explain exactly why 
addictive substances are so pleasurable -- and why some people get easily 
hooked, but others don't.

Fresh scientific insights suggest drug addiction may largely be explained, 
and potentially treated, as a medical problem rather than a societal one, 
just as Prozac did for depression.

Based on these insights, small companies and independent researchers are 
starting to develop a new array of antiaddiction drugs. Early experiments 
in animals and people suggest these medicines have promise, although it 
will likely be several years before they are available to consumers.

Many researchers are studying dopamine, a pleasure-causing chemical in the 
brain that transports messages from one nerve cell to another. Usually, 
only a certain number of dopamine receptors in the brain are turned on in 
response to low levels of the chemical. But when a user has an alcoholic 
drink or snorts cocaine, that steady dopamine flow suddenly becomes a flood 
and lights up many more receptors.

NeuroSearch AS of Denmark is developing an anticocaine and antialcohol drug 
that raises the body's normal level of three chemicals -- dopamine, 
serotonin and noadrenalin -- and thereby boosts the pleasure a person 
feels. "It fools the brain into thinking that the person has taken alcohol 
or cocaine," says Ole Graff, medical director for NeuroSearch. Unlike 
cocaine, though, NeuroSearch's drug enhances the user's mood in a gentle 
and gradual way. Animal tests suggest the company's drug isn't addictive.

The drug proved effective when it was given to cocaine-taking rats and 
monkeys, and it was shown to be safe in early-stage clinical trials with 90 
people. Dr. Graff says early-stage tests with cocaine addicts showed "they 
no longer had any craving" for cocaine. He concedes longer-term studies are 
needed to prove the drug really works.

Scientists at the Brookhaven National Laboratory in the U.S. have pinned 
their hopes on Vigabatrin, an epilepsy drug sold in Europe, but not 
available in the U.S. In a test in February, 20 rats were given the choice 
of drinking from three bottles containing water, alcohol, or a mixture of 
alcohol and cocaine. The rats got hooked on the alcohol-cocaine mix. They 
were then injected with Vigabatrin. Within two weeks, they spurned the 
alcohol-cocaine bottle and chose to drink only water.

"It was really quite striking," says Stephen Dewey, who specializes in 
addiction research at Brookhaven. "It was as if the animals never got the 
alcohol and cocaine."

Vigabatrin works by lowering dopamine levels. A person's normal dopamine 
level fluctuates 20% to 30%, but cocaine makes it shoot up 500%. Vigabatrin 
brings that level down to the normal 20%-to-30% range, Dr. Dewey says.

Vigabatrin has shown equally promising results in animal studies using 
heroin, amphetamines, Ecstasy and nicotine. Human trials could start by 
year end, according to Catalyst Pharmaceutical Partners of Florida, which 
has licensed the rights to develop Vigabatrin for drug addiction.

Such treatments have limitations. Drug abusers may be able to overpower any 
dopamine-reducing effects simply by taking bigger doses of cocaine or 
alcohol. Also, Vigabatrin's effects kick in only after two weeks, so it 
isn't likely to work for a person seeking a quick response. Some scientists 
say dopamine's role in addiction may be only part of the story: One 
experiment with genetically engineered mice showed that although they 
lacked the target to which cocaine molecules attach themselves, the animals 
still craved their cocaine fix. The upshot: "Most likely other chemical 
systems in the brain, like serotonin," are involved in addiction, says Mark 
Caron, a scientist at Duke University in North Carolina, which did the 
tests on mice.

Another possibility is a vaccine. Nabi Biopharmaceuticals tested an 
antinicotine vaccine in animals and was able to reduce nicotine levels in 
their brains by as much as 64%. Early last month, the Florida firm began 
human tests. DrugAbuse Sciences Inc. of California is developing a similar 
vaccine for cocaine.

Xenova of Britain may be furthest along in developing both a cocaine and 
smoking vaccine. Both substances' molecules are tiny enough to sneak 
through the blood-brain barrier -- a semipermeable mesh that protects the 
brain from foreign or harmful substances. To prevent the invasion, 
scientists decided to make the nicotine or cocaine molecules larger, 
thereby blocking their entry into the brain and preventing the user's "high."

Xenova's smoking vaccine is partly made from a cholera vaccine, which 
triggers antibodies in a patient's body. Once these antibodies bind to the 
nicotine molecules, they are too large to easily slip into the brain. Based 
on early-stage human trials, "we clearly have a product that is safe," says 
David Oxlade, the company's chief executive. But Xenova says a commercial 
product isn't expected to be ready before 2006.

Other researchers are betting on more unconventional approaches. One is 
ibogaine, a hallucinogenic drug derived from the roots of an West African 
shrub, which showed some success when used in underground treatments in the 
1990s in Holland. Its reputation was tarnished when two women died after 
taking it. Still, several academic papers and anecdotal evidence point to 
its antiaddictive qualities.

Deborah Mash, a pharmacologist at the University of Miami, is a believer. 
With the backing of the government of St. Kitts, she has supervised the use 
of ibogaine to treat about 300 patients on the Caribbean island. Dr. Mash 
says most of those patients were American, and they paid about $10,000 for 
12 days of treatment.

In February, Dr. Mash and colleagues at the University of Miami were 
granted patents for an ibogaine metabolite, a compound that is produced 
when a drug undergoes chemical changes in the body.

Dr. Mash has a green light from the U.S. Food and Drug Administration for 
clinical trials of ibogaine. But she wants the FDA's approval to test the 
metabolite. Her other challenge: To find a company willing to commercialize 
the drug. "There are desperate addicts screaming for this," she says. "Now 
it all comes down to money."
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MAP posted-by: Jay Bergstrom