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."