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Wall Street Journal (US) Mon, 15 Jul 2002
AN ARRAY OF NEW DRUGS SHOWS PROMISE IN FIGHTING ADDICTIONS
by: Gautam Naik
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."
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"Ibogaine forces you to have a scathing self inventory of yourself. You're forced to confront your fears and deal with them until you come out understanding a little bit better. Each person's journey through recovery is highly individualized."
-G.H., Ibogaine patient
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