THE ADDICT'S BRAIN

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.

WITH MIKE ELKIN IN MADRID

© 2004