AN ARRAY OF NEW DRUGS SHOWS PROMISE IN FIGHTING ADDICTIONS

Could people be inoculated against drug addictions the way they can against
some infectious diseases?

It may be possible. Despite disappointing past efforts to treat addictions
with medicine, recent research indicates the approach has merit. In one
study, about 50 smokers in Belgium were injected with an unusual drug ,
code-named TA-NIC. After taking as many as five doses in 10 weeks, two of
the study's subjects quit smoking. Several others reported less desire to
smoke, says 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 again.

Vaccines are just one of several new medical approaches to fight the
escalating problem of addiction. Some 3.2 million Americans and 1.2 million
people in Western Europe 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 a staggering $300 billion each
year in the U.S. alone.

Past efforts to fight addiction with medicine have been plagued by high
relapse and dropout rates. And despite the huge revenue opportunity, big
drug companies have barely gotten involved, largely because of the
perceived stigma of dealing with a disreputable part of society. But the
obvious need for antiaddiction treatments continues to make the field
attractive. Last week came news that several scientists from
GlaxoSmithKline PLC and Roche Holding AG are breaking away from their
parent companies to form a Swiss company, Addex Pharmaceuticals, that will
focus on compounds for nicotine, alcohol and cocaine dependence.

In pursuing medical solutions to addiction, some 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 affects many more receptors.

Denmark's NeuroSearch A/S 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, Neuro-Search'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 was shown to be safe in early-stage clinical trials with 90
people. Dr. Graff says early-stage tests with cocaine addicts showed that
"they no longer had any craving" for cocaine. He concedes that longer-term
studies are needed.

Scientists at the Brookhaven National Laboratory in the U.S. have pinned
their hopes on Vigabatrin, an epilepsy drug sold in Europe but unavailable
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.

Vigabatrin works by lowering dopamine levels. A person's normal dopamine
level fluctuates by 20% to 30%, but cocaine makes it shoot up 500%.
Vigabatrin brings that level down to the normal 20% to 30% range, says
Stephen Dewey, who specializes in addiction research at Brookhaven.

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

Dopamine-reducing treatments have limitations. Drug abusers could overpower
therapeutic effects simply by taking bigger doses. Also, Vigabatrin takes
two weeks to have an effect. And 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 a 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, which did the tests on mice.

Taking the vaccine approach, Nabi Biopharmaceuticals tested an antinicotine
vaccine in animals and cut nicotine levels in their brains by as much as
64%. Last month, the Boca Raton, Fla., firm began human tests. DrugAbuse
Sciences Inc., Menlo Park, Calif., is developing a similar vaccine for cocaine.

Britain's Xenova 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; to prevent that, scientists made the
molecules larger, thereby blocking their entry into the brain and
preventing the user's "high."

Based on early-stage human trials, "we clearly have a product that is
safe," says David Oxlade, Xenova's chief executive. "More important, we
have demonstrated that both smokers and nonsmokers who were given the
vaccine produced nicotine-specific antibodies." But Xenova says a
commercial product isn't expected before 2006.

Another approach involves ibogaine, a hallucinogenic drug derived from a
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, academic papers and anecdotal evidence
point to its antiaddictive qualities.

Deborah Mash, a pharmacologist at the University of Miami, believes in
ibogaine. Backed by the government of St. Kitts, she supervised use of the
drug to treat about 300 patients on the Caribbean island. She says most of
the patients were American, and that they paid about $10,000 for 12 days of
treatment.

In February, Dr. Mash and colleagues won patents for an ibogaine
metabolite, a compound produced when a drug undergoes chemical changes in
the body. Dr. Mash believes that the metabolite won't have the unwanted
mind-altering effects that ibogaine has. She has a green light from the
U.S. Food and Drug Administration for clinical trials of ibogaine but wants
the FDA's approval to test the metabolite. She also must find a company
willing to commercialize the drug . "There are desperate addicts screaming
for this," she says. "Now it all comes down to money."