THE ADDICT'S BRAIN

Jose Galan was 30 years old when he realized that alcohol was consuming his life. As a student at the Complutense University of Madrid, Galan would often go out with his friends in the evening for a drink, but after a while he found himself sitting at the bar stool during the day, when he should have been in class. Galan did what most problem drinkers never do: he sought medical help. "At first the doctors just told me to stop drinking," he says, "but that doesn't work." Then they sent him for psychotherapy, gave him "anticompulsion" drugs that are supposed to inhibit cravings and on two occasions even put him in the hospital.

These measures would work for a week or two, but each time Galan quickly relapsed. Finally, Galan saw Dr. Gabriel Rubio, head of the alcoholism program at the Retiro Center for Mental Health in Madrid. Rubio tried an unconventional treatment: he prescribed topiramate, a drug that's usually used to prevent seizures in epileptics. Now, 10 months later, Galan hasn't had a drink, and he's even been able to stop overeating.

Scientists have long theorized that all addictions, from drugs and alcohol to binge-eating and smoking, were somehow connected. But in the past few years, they've been taking this notion out of the realm of fancy and into the laboratory. A spate of drugs, including topiramate, have been found to work for several types of addictions at the same time. And researchers have begun to uncover brain chemistry that most addictions have in common. As a result, scientists believe that doctors may soon have drugs to prescribe for addictions of all sorts--and many are more optimistic than ever before about prospects for a single cure-all drug that would do for addiction what Prozac did for depression.

The stakes are high: addictions exact a heavy toll. Every eight seconds, somebody dies of a tobacco-related illness, according to the World Health Organization. And the social consequences of alcohol abuse are mind-boggling. A Swedish study recently found that 16 percent of violent crimes were committed not by crack or heroin addicts, but by drunks. Obesity afflicts 100 million people in the United States and Europe, and untold numbers are binge eaters. Addicts often hide their afflictions, and doctors often ignore them. Experts believe that a single anti-addiction drug might bring sufferers out of the closet. Recognizable brand names create social acceptance: it's easier to tell a spouse that you're taking a pill if you each know friends who take it, too.

At the moment, topiramate is the leading candidate for a silver-bullet drug. A study of hard-core drinkers, published in the September issue of Archives of General Psychiatry, had promising results with alcohol: drinkers who took topiramate were six times more likely than those on a placebo to remain abstinent for three months. A third of the treated patients shifted from heavy drinking to moderate consumption, and almost one in five stopped drinking altogether. Topiramate may be up to four times more powerful than the current alcoholism meds, acamprosate and naltrexone. And since drinkers don't have to go dry to take topiramate, they might be more inclined to seek treatment.

The Archives study also found topiramate to be effective for other addictions. Half the treated patients lost weight, and one in five quit smoking cigarettes--even though no one was asked to. Study author Dr. Bankole Johnson, a neuroscientist at the University of Virginia, reported that the drug doubled his patients' chances of scoring well on measures of well-being like social functioning and physical health.

What might keep topiramate from becoming the next Prozac, though, are two annoying side effects: drowsiness and difficulty calling up words. Johnson, who's prescribed the drugs to many alcoholics, insists that "the cognitive difficulties are trivial compared to those caused by alcohol." And manufacturer Johnson & Johnson is devising a time-release version that may be easier to get used to. But other factors, including a slight risk of acute glaucoma and kidney stones, may stand in the way of widespread use. "One of the reasons Prozac was so popular is that general practitioners can prescribe it," notes New York psychiatrist Timothy Walsh.

Scientists have other promising candidates. For instance, a study of how marijuana produces the "munchies"--a food craving--has led to another drug, rimonabant, that also depresses appetite and seems to reduce cravings for nicotine and alcohol. Drug giant Sanofi-Aventis recently announced a plan to market it as a diet pill in 2006 under the brand name Acomplia. Peter Kalivas, a neuroscientist at the Medical University of South Carolina who has studied addiction in animals, believes the key is to zero in on glutamate, a neurotransmitter active in cravings. (Several of the drugs being studied act in a broader way more likely to have unwanted side effects.) Kalivas scanned the brain response of 13 cocaine addicts while they looked at photos of people smoking cocaine. Then he gave the participants glutamate-inhibiting N-acetylcysteine, now used to treat Tylenol overdoses and cystic fibrosis, and scanned their brains again. He found that the drug dramatically reduced the subjects' arousal response.

Another biochemical target for anti-addiction drugs is gamma-aminobutyrate, or GABA, which keeps a normal brain in a state of inhibition. In addicts, the brain releases so much glutamate when they see or taste a martini or a cigarette that the GABA receptors are overwhelmed--desire trumps self-control. The nucleus accumbens, a tiny part of the brain's emotional center located at about the height of the eyebrows, becomes flooded with dopamine, a neurotransmitter associated with pleasure, making it more fun for an addict to drink than go home and tuck the kids into bed. So one promising strategy is to stimulate more GABA. Baclofen, a muscle relaxant that does exactly that, was shown in a 2002 trial in Italy to reduce the yen for alcohol. That same year, researchers reported that giving baclofen to rodents stopped them from "self-administering" cocaine, heroin, nicotine and methamphetamines. Scientists don't yet know whether topiramate, baclofen--or any other existing drug--will become the Prozac for addiction. The trick will be to find the one that most efficiently targets the essential brain systems, while leaving the rest free for happier pursuits.