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Unlocking anatomy of addiction

Everyone, it's fairly safe to say, knows someone who is addicted to something - but not everyone knows why. In scientific circles, addiction is regarded as a disease of the brain, with ongoing research showing great promise for treatment involving medications now under development. Despite scientists' efforts to change attitudes, addiction still often is considered a shameful matter, attributed to a lack of willpower or failure of character.

"We no longer use that term, 'addictive personality,' because it isn't really personality, but the interaction between a drug and a person," says Dr. Charles O'Brien, professor of psychiatry at the University of Pennsylvania Health System and director of its treatment research center.

"For example, if 100 children are exposed to cocaine and they try it, 16 percent will become addicted, but the rest won't. The worst drug for producing addiction is nicotine. If 100 kids try smoking, about 32 percent will become addicted," he says.

"There is a basic neuroscience of addiction, which of all mental illnesses — including bipolar and schizophrenia — is better understood at the brain level," Dr. O'Brien explains, "partly because drugs are very specific and we have very good animal models."

Some 72 risk factors are critical to consider when speaking of addiction, Alan Leshner, chief executive officer of the American Association for the Advancement of Science and former head of the National Institute on Drug Abuse, told a Library of Congress audience earlier this year in a lecture titled "The New Science of Addiction and What it Means for Society.""

"So you have to think about a precise person when you think about an addicted individual," he said.

He spoke of his own efforts to quit smoking after 19 attempts, which he did 27 years ago, and how he can now "occasionally experience phenomenal cravings through activities associated with tobacco use. That craving causes brain activity."

The brain over time, he said, "is changed in fundamental and long-lasting ways persisting long after you stop using drugs." That change produces the condition that we call addiction, he noted, saying "effects persist not only in the brain but in cognitive learning functions."

Of all the various systems in the brain — aural, visual, etc. — the one Dr. O'Brien calls the reward system seemed designed early in evolution to motivate behavior.

"It turns out there are drugs that, by coincidence, activate the reward system very intensely — far more than by natural rewards from sex, food — or even winning at football," he explains. "If you study anything when young, you develop a better reward system. If you start at age 14, you are a more efficient smoker than at age 21, and the same for other addictions."

As for the definition of addiction, he is inclined to include compulsive shopping, Internet use and gambling, but the final word on these won't be out until 2012, when a revision of the psychiatric profession's standard reference book is due.

Meanwhile, based on studies of memory processing, what is clear, he agrees, is that addiction as a disease or disorder involves leaving memory traces laid down in circuits in the brain. It's much like a person who learns to ride a bicycle at a young age won't forget how even if he doesn't ride again for years, "because there is a physical change in the brain," Dr. O'Brien says. "If you take too much cocaine, you can lesion the brain, and you can do that with alcohol. Circuits are overlearned when you are an addict."

Research also has shown that receptivity to one addictive drug or another is largely an individual physiological process, depending a great deal on a person's genetic makeup, although Dr. O'Brien agrees that development of addiction is also determined partly by environmental factors like advertising and peer pressure.

"If you have only one addiction-prone gene, you are not as likely to become addicted," he says. Researchers have identified a gene that influences the way a brain responds to alcohol, for example; a variant for this gene can be found in about 25 percent of European-Americans, thereby increasing their risk of becoming an opiate addict or an alcoholic.

To date, a medication called naltrexone, originally developed for heroin addiction, "works for a certain sub-type of alcoholism," Dr. O'Brien says, with a single injection protecting a person for one month.

No one is totally resistant to addiction, although "some develop it more easily than others," says David McCann, chief of the medications discovery and toxicology branch at the National Institute on Drug Abuse in Rockville.

"By learning about how brain systems are affected in all animals and people, we identify targets to pursue for medication," explains Dr. McCann, who works on animal models, studying especially cocaine and methamphetamine dependence. "It's really important to follow genetic differences, but we have to follow many paths."

One of the ways that cocaine changes the brain is to affect a pleasure-enhancing neurotransmitter called dopamine.

"Scientists have found that a different neurotransmitter, called GABA, has an opposite effect on dopamine," Dr. McCann says. "One of the drugs of promise regarding treatment is vigabatrin, which boosts brain levels of GABA, fights the effect of cocaine on dopamine, and reportedly decreases craving for cocaine."

It also has been shown to be effective in blocking anxiety — an important discovery, Mr. McCann points out, "because stress often is reported as a triggering event sending people back to drugs such as cocaine."

While there has been a lot of progress in understanding the brain and addiction, Mr. O'Brien finds progress in delivering better care hampered by "not enough trained physicians who can deliver this care."

He is aware of just one medical school — the University of Pennsylvania — that makes compulsory a full course on addiction.

Complicating the therapeutic picture is the fact that no single treatment works for everyone.

"A good therapist must be flexible and able to tailor treatment to the individual and have knowledge of scientific literature," Mr. O'Brien says. He believes in "talk therapy" — often called cognitive behavior therapy — but says "the best results occur with medication."

"Drug addiction treatment does work," declared Mr. Leshner in his talk. "It is a biological illness just like others. So the 'war on drugs' is the worst metaphor. Simply taking the criminal justice approach doesn't work. If we treat addicted offenders, they won't come back. That is the truth. Addicts put in jail have about a 70 percent chance of being arrested again if they are not treated; when treated, flip the numbers."

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