Investigating the scientific basis of narcotic addiction

“This is an exciting time to be working in drug abuse research,” says Dr. Charles Chavkin, an expert on the basic science of narcotic addiction. “We are just beginning to understand the nervous system well enough to be able to describe these diseases and understand their effects at a cellular and molecular level.”

As a scientist, Chavkin, who is professor of pharmacology in the School of Medicine and associate director of the UW’s Alcohol and Drug Abuse Institute, would like to see public policy on addictive drugs based on scientific discoveries rather than intuition and assumption.

He sees some societal ideas about addiction slowly changing as a better understanding of the disease develops. These changes are very evident in our debates about tobacco: people are learning that there’s a difference between a habit and an addiction, that will power may not be enough for someone to quit using an addictive drug, and that there’s something besides a “moral failure” going on in addiction.

Charles Chavkin in his lab , Photo by Gavin Sisk

“When we really understand the nature of the disease, then we can decide as a society how to handle the problem of drug addiction more rationally and effectively,” he says.

Chavkin will speak about his work in a Science in Medicine lecture at noon, Thursday, Feb. 10, in room T-625 of the Health Sciences Center. His topic is “Opiate Dependence and Addiction from a Cellular and Molecular Perspective.” The Science in Medicine series is sponsored by the School of Medicine’s Office of Research and Graduate Education.

Since he was a graduate student at Stanford in the late 1970s, Chavkin has been working on the biochemistry and electrophysiology of opioid action in the brain. The body makes its own opioid substances - such as the endorphins released by vigorous exercise and during painful experiences. The opiates used as drugs, such as morphine, are produced naturally by plants. Their use to ease pain probably dates back to primitive humans and their ability at high doses to produce addiction is an old story, too.

But a lack of knowledge about how these substances really produce their effects on human behavior has made it harder for people to understand the distinction between addiction and physical dependence.

“When opiates are used to control pain, they do not produce the kind of intense orgasmic rush that they do at high doses,” Chavkin says. Addiction very rarely results from use to control pain, he notes, and yet there is a widespread and inappropriate public fear about using opiates to control pain caused by cancer, for example.

Developing a tolerance for an opiate as a result of long-term use is not the same thing as developing an addiction, he says, because it does not involve the large doses and euphoric effects.

By studying how opiates work in the brain at a cellular and molecular level, Chavkin and other researchers have learned many ways in which receptors on cells and the strength of synapses that conduct nerve impulses are altered in addiction.

“The idea that drugs or alcohol do their damage by killing brain cells is obsolete,” he says. “That only happens after a long period of very heavy use and is not required for drug addiction.

“But what laboratories like mine are demonstrating is that high doses of opiates cause profound changes in the brain’s synapses and that these changes are very long-lasting. We believe these changes in the structure and function of nerve tissue and nerve conduction are at the base of the craving people feel long after they are not taking the drugs anymore.”

Chavkin and his colleagues use many techniques to study these questions, including biochemical and electrophysiologic examinations of nerve tissue and genetic manipulation of protein expression.

In the long run, he believes that as work in his laboratory and others defines the nervous system changes that occur in opiate addiction, the chance of finding a way to reverse or block these changes will increase.

“I do think that in the future we may be able to find ways to reverse the biological changes that addiction causes,” he says.

Chavkin is a graduate of Cornell University and earned his Ph.D. in pharmacology from Stanford University in 1982. He joined the School of Medicine’s Department of Pharmacology in 1985, after conducting postdoctoral research at the Salk Institute and Scripps Clinic and Research Foundation in La Jolla, Calif.

Since joining the UW faculty, he has been a member of the interdisciplinary graduate programs in Neurobiology & Behavior and in Molecular & Cellular Biology. In 1991 he became associate director of the Alcohol and Drug Abuse Institute.

He is a member of several national and international neuroscience and pharmacology organizations and is now serving a four-year term as principal organizer of the International Narcotics Research Conference. ¶

Claire Dietz