Betting on a Cure

McNeilly plans to recruit about 20 people who are healthy except for their gambling addictions, people who "have truly tried to stop gambling, but can't," he says. (His experiment has no control group, which means that his results won't be conclusive, but they could potentially point the way for further research.) He will give all of his gamblers Acamprosate three times a day for eight weeks, and then ask them to evaluate their cravings in that time period. "These are individuals who arrange their days and their lifestyles around gambling. They are thinking about it all day long," he says. "So we'll want to see if they still plan their days around it, and if they actually do bet less. We want to know how people experience taking this drug: What kind of difference does it make in their lives? The whole idea is that ultimately we want to help people get to a point where they can have fewer cravings so they can say, 'Gee, this isn't as much fun anymore.'"

There are two main problems the trials might run into: Either the drugs won't work, or they'll work a little too well. The first objection is backed up by other studies that have shown that drugs designed to tamp down urges may have limited success. Studies of Acamprosate have shown that when the drug works in alcoholics, it does so only if used in combination with counseling and group therapy. And studies of Naltrexone have gone both ways: Some paint it as a huge success, but others are more skeptical. One recent trial published in the Journal of Clinical Psychiatry found that almost 40 percent of patients who took Naltrexone managed not to gamble for at least a month (the placebo rate was a comparatively measly 10 percent). But another trial of Naltrexone and gamblers, published in the Annals of Clinical Psychiatry in 2002, found that the drug was less likely to help "patients with poorer social and occupational functioning due to urges and thoughts about gambling"—in other words, those who need help the most.

Mark Stacy, a neurologist at Duke University, says he's tried using this type of drug in Parkinson's patients, who sometimes develop compulsive gambling behaviors as a result of medications that boost their dopamine levels. (In Parkinson's, the brain's dopamine-producing neurons atrophy and die, so many drugs used to treat the illness affect the dopamine "pleasure" pathways, often with unexpected results.) "Nothing really seems to work [to treat gambling addiction in those patients]," he says. "We've never been able to treat compulsivity very well."

Part of the problem, according to Stacy, is that drugs like Naltrexone are targeting the "D2" dopamine pathway in the brain, which is associated with rewards, but not another pathway, "D1," which is more closely associated with compulsive behaviors. "The next wave of addiction treatments," he says, will need to attack both pathways instead of "just going after one neurotransmitter constellation." It's possible, he adds, that just going after the D2 dopamine pathway could make gambling problems even worse, since the compulsion pathway will still be open for business.

The second objection—that dopamine blockers might work too well—centers on the basic mechanism of Naltrexone, which is a crude one. Because it works by stopping the brain from processing the chemical that makes an activity feel good, it could cause some patients to lose pleasure in other areas of life. Studies show that Naltrexone treatment doesn't trigger depression in most patients, but Grisel says that the drug might make some of life's most fun activities seem "gray and uninspiring" to former addicts. "If someone's just sitting at their desk having a regular day and they took this drug, they wouldn't be able to tell a difference," she says. "But if they were about to have sex or listening to a concert by their favorite band, they probably wouldn't enjoy that as much."
 
Ultimately, that may turn out to be the biggest problem with these drugs. Forget for a minute how well they work: If losing the capacity to experience joy is a risk, what patient would be willing to take them?

© 2008