Wired But Why?

Studies of cells in the brain may explain why some people are more likely than others to become hooked on drugs


It wrecks neighborhoods, families and lives, and might be the most important public health problem faced by Western societies. Yet since chemists first isolated cocaine, morphine and heroin in the 19th century, physicians and scientists have struggled to explain the nature of addiction.

There is still much to learn, but with advances in genetics, medical imaging technology and neuroscience, scientists say they are closer than ever to understanding why some people who try drugs become addicted, and some do not.

"I think we made more progress in the last 10 years than in the previous history of mankind," said Frank Vocci, director of treatment and research at the National Institute on Drug Abuse, which spends $1 billion annually on drug research.

"We're a heck of a lot further along than we were 30 years ago," said Dr. Paul R. McHugh, a psychiatrist at the Johns Hopkins School of Medicine. That progress, he added, "tells me that we don't have to be quite as hopeless as we were before about addicts."

In the past decade, scientists have come to recognize that genetics plays a major role in all addictions.

It was long suspected that alcoholism was at least partly inherited because of its presence in some families and not others. But studies of addicts in Baltimore, Japan and elsewhere have shown that methamphetamine users, heroin addicts and other habitual drug users share similar variants of dozens of brain receptor genes.

One day, scientists say, genetic testing could enable drug counselors to warn parents if their children carry an unusually high risk of addiction, or tailor existing treatments to individual drug users. But the ultimate hope, of course, is that the genetics of addiction will help find powerful new treatments.

So far, the development of new addiction treatments has lagged far behind the basic science. "There have been modest, incremental improvements," said Dr. Solomon H. Snyder, a Johns Hopkins neuroscientist and psychiatrist who is one of the world's authorities on the biochemistry of addiction.

In general, he said, advances have come slowly because major pharmaceutical companies see little profit in tackling the problem.

But by defining what addiction is, researchers have helped the pharmaceutical industry identify what it calls "targets" for drug research - genes, proteins, neurotransmitters that could be modified to block the compulsive use of drugs.

One thing that addiction is not, scientists say, is a simple inherited illness. There is no single gene that inevitably leads to habitual drug use. Instead, some people appear to carry an array of genes that raises their risk of addiction.

"Nobody has to become addicted," said Dr. George R. Uhl, a clinical neurologist and chief of the National Institute on Drug Abuse's molecular neurobiology branch at Hopkins' Bayview campus.

"Genes have an influence on behavior," McHugh said. "They're not a determining influence on behavior, in that if you've got them there's nothing you can do about them. They are an influence."

Overall, researchers say, about half of an individual's susceptibility to addiction is inherited, while the other half is the product of a person's environment - which includes the pressures of family, peers and neighborhood.

Discussions of addiction usually focus on people living in the most desperate circumstances, in the poorest neighborhoods. But the problem, of course, extends far beyond the inner city.

A brother lost

Lee Krol was a skilled marine electrician, homeowner and father who lived in Pasadena. But he had a problem that anguished and mystified his family for most of his life. As a teenager, he began to drink and use drugs. While he would quit for a while, it was never for good. "There's nothing like this stuff," he once told his brother, Tom.

So his family was devastated, but not surprised, when they found the 50-year-old on the floor of the computer room of his home Dec. 7, dead of a heroin overdose. "I want him to be portrayed as a good person," said Tom Krol. "He just had a terrible disease."

Since the early 1970s, scientists have identified all of the brain cell switches, called receptors, which respond to addictive drugs. Using advanced imaging technology such as MRI machines and PET scanners, they have been able to watch as drugs alter the way the biochemical signals called thoughts and feelings are transmitted through the brain.

Addiction research has zeroed in on a group of brain cells in the nucleus accumbens, nestled deep within the brain, the location of what has been called the "pleasure reward" system. Many of the brain cells, or neurons, in this network communicate with each other with two of the brain's chemical messengers, serotonin and dopamine.

The system produces feelings of well being, the reward for engaging in actions such as eating and sex, vital to survival and reproduction. Illicit drugs, it turns out, switch on this system - specifically, by raising the level of dopamine available to neurons.

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