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." - --- MAP posted-by: Jay Bergstrom