Craving, Chemistry,
and Co-morbidities

Testing the substance of addiction research


Cigarettes. Gambling. Cocaine. Sex. Alcohol. Work.

The roots of addiction span a vast landscape of need and run deep in the human brain. Craving rises from the amygdala, one of the most ancient parts of the brain. And in all of human history, only the native people of Alaska have not developed a psychoactive substance integral to their culture. That, some say, is only because so little grew in their cold climate.

As participants in an Emory faculty seminar discovered last year, however, addiction is as social as it is biological. How else could we become addicted to activities, like gambling, as well as substances, like cocaine? Each week, clinicians, bench scientists, and scholars in this group of about twenty faculty gathered to discuss such questions. School of Public Health dean Jim Curran; Center for Health, Culture, and Society director Randall Packard; and Science and Society director Arri Eisen collaborated to form the seminar. Howard Kushner, Nat Robertson Professor of Science and Society, organized readings and led discussion. Whether talking about rats, people, or culture, seminar participants repeatedly questioned their own understanding of the term “addiction."

The laboratory of addiction

One seminar participant, Michael Kuhar, neuroscience division chief at Yerkes Regional Primate Center, is leading a team that investigates addiction at the molecular level. Pinpointing the molecular site in the brain where cocaine takes effect has allowed Kuhar and his collaborators to develop cocaine analogues—drugs that behave like cocaine but lack many of its negative effects.

Both like cocaine and significantly different, these analogues may one day be used to treat cocaine addicts, just as methadone helps some people dependent on heroin. While the analogues reduce craving by acting on the same molecular site in the brain as cocaine, the effect is less toxic and longer-lasting. Kuhar works with a biotechnology company, Addiction Therapies, Inc., that plans to test the cocaine analogues in humans as early as next year. Studies in other labs with animal models suggest that a vaccination to prevent drug use is on the horizon.

One day, Kuhar says, treatment may go something like this: “Someone comes in and receives our medication to help him stop his out-of-control, often illegal behaviors. Relying on this medication binds him to the treatment program and all it offers. The next step may be to vaccinate him against the drug, so that if he relapses, the drug just won’t have the same effect.”

The addictive drug would be stopped in its tracks by antibodies in the addict’s own blood. Labs at Yale and Columbia have developed a vaccine that stimulates antibodies that bind to the tiny cocaine molecule, preventing it from reaching the brain and causing a high. Since the vaccine does not stop the cocaine analogue from reaching the brain, the two treatments could be used in tandem.

Even if such a medicine for cocaine addiction proves safe and reliable, experts predict many other approaches will be needed to address addiction fully. Since dependence has complicated physiological effects and roots in genetic and social circumstances, says Kuhar, “there’s not going to be a single, magic bullet.”

The search for supernormals

Growing numbers of experts say effective treatment demands a better understanding of the interaction of the biological and social aspects of addiction. National Institute on Drug Abuse chief Alan Leshner, who spoke to the faculty seminar last fall, has crusaded to make addiction understood as a brain disease that manifests in compulsive behavior. Yet researchers find that dependent behaviors defy easy categorization.

“Addiction may be more like a syndrome than a distinct disease,” says seminar moderator Kushner. “It could be a label for a group of behaviors that all have different

The tendency of addiction and other diseases to travel in packs also bedevils attempts to define the nature of dependency. Researchers call this synchronicity among illnesses—such as depression’s tendency to accompany alcoholism or heroin’s link to hiv/aids—”co-morbidity.” The faculty seminar confronted a complex chicken-and-egg question: Does the drug change the addict’s brain chemistry, or does the drug do something for the addict because of an underlying condition? According to Kushner, “That’s where the jury is still out.”

Co-morbidities offer important clues to the workings of many diseases. Discovering, for instance, why schizophrenics and people with attention deficit hyperactivity disorder seem frequently to self-medicate with cigarettes may lead to a better understanding of the neurobiology of those diseases.

Untangling the knot of co-morbidities, though, “really reveals the gap between the medical or laboratory researchers and the social scientists,” says Claire Sterk, chair of the Department of Behavioral Sciences and Health Education in the School of Public Health. “In the lab, you isolate a substance to test its effects. That makes taking co-morbidities into consideration very difficult,” says Sterk, who has studied addicted populations for twenty years.

Just to get a control group for a neuroimaging study of cocaine’s effects on emotion, for example, the research group of Karen Drexler, assistant professor of psychiatry and behavioral sciences, had the daunting task of finding human “supernormals.” These are people free of cocaine addiction and other dependent behavior or psychiatric conditions—even minor neuroses. Though they found a few such rarefied creatures, Drexler admits that co-morbidities represent an important challenge to clinical research.

For social scientists too, analyzing the impact of co-morbidities is anything but straightforward. The social context of drug use makes life and death differences, but the logic of addictive behavior is often surprising, says anthropology professor Peter Brown. For example, using heroin in a group would seem to increase the deadliness of the activity through exposure to illnesses like hiv/aids. But studies show that addicts who shoot up alone actually die more often. “There’s simply no one to pick up the phone and call 911 when someone overdoses,” Brown explains.

Though the social context of drug use is key, social education programs eventually hit a brick wall in reducing usage. “Organizations like the American Cancer Society are set up on the principle of ‘education as a solution.’ When that doesn’t work, they’re stuck,” says Arri Eisen.

Cigarettes, still the most deadly addiction in America, according to Drexler, illustrate the limits of education and the promise of interdisciplinary research. In the last three decades, the American Lung Association reports that the number of Americans who smoke dropped by 40 percent, largely because of massive educational campaigns
and shifts in social attitudes. A team of Emory researchers including Drexler, Sterk, Kushner, and psychology professors Darryl Neill and Irwin Waldman hopes to discover why a quarter of smokers remain addicted.

Like addiction specialists across the nation, these diverse researchers have been energized by the concurrence of social losses and scientific gains. Some speculate that the blatant failure of America’s “War on Drugs” will open doors to new approaches in drug treatment and policy. At the same time, technological advances and interdisciplinary efforts promise to pin down a disorder that has been as nebulous as clouds and as common as dirt. A.B.B.