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Vaccines for Addiction
WSJ 7/5/02
Drug Makers Test Vaccines And Drugs to Halt Addiction
By GAUTAM NAIK
Staff Reporter of THE WALL STREET JOURNAL
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."
Write to Gautam Naik at
gautam.naik@wsj.com
Updated July 5, 2002 12:19 a.m. EDT
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