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Nora Volkow, director of the National Institut...

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From heroin and cocaine to sex and lies, Tetris and the ponies, the spectrum of human addictions is vast. But for Dr. Nora D. Volkow, the neuroscientist in charge of the National Institute on Drug Abuse, they all boil down to pretty much the same thing. She must say it a dozen times a day: Addiction is all about the dopamine. The pleasure, pain and devilish problem of control are simply the detritus left by waves of this little molecule surging and retreating deep in the brain.

A driven worker with a colorful family history and a bad chocolate problem of her own, Dr. Volkow, 55, has devoted her career to studying this chemical tide. And now, eight years into her tenure at the institute, the pace of addiction research is accelerating, propelled by a nationwide emergency that has sent her agency, with a $1.09 billion budget, into crisis mode.

The toll from soaring rates of prescription drug abuse, including both psychiatric medications and drugs for pain, has begun to dwarf that of the usual illegal culprits. Hospitalizations related to prescription drugs are up fivefold in the last decade, and overdose deaths up fourfold. More high school seniors report recreational use of tranquilizers or prescription narcotics, like OxyContin and Vicodin, than heroin and cocaine combined. The numbers have alarmed drug policy experts, their foreboding heightened by the realization that the usual regulatory tools may be relatively unhelpful in this new crisis.

As Dr. Volkow said to a group of drug experts convened by the surgeon general last month to discuss the problem, ÒIn the past, when we have addressed the issue of controlled substances, illicit or licit, we have been addressing drugs that we could remove from the earth and no one would suffer.Ó

But prescription drugs, she continued, have a double life: They are lifesaving yet every bit as dangerous as banned substances. In other words, these drugs must be somehow legal and illegal, encouraged yet discouraged, tightly regulated yet easily available. The experts are looking to the institute for scientific tools that might help by loosening the tight bonds between pain relief and addiction in the brain. And that, Dr. Volkow told her audience with a small smile, is all about the dopamine.

In medical school she read an article in Scientific American about one of the first American positron emission tomography scanners, able to photograph not only the brainÕs structures but also its invisible processes. She never looked back. After a residency in psychiatry at New YorkUniversity, chosen because it owned that PET scanner, she took a job in Houston, then transplanted her research to Brookhaven National Labs on Long Island, home of groundbreaking research into dopamine and PET scanning.

Dr. VolkowÕs research career, still based at Brookhaven, has been notable for its Òbrilliant science,Ó said Don C. Des Jarlais, an expert in drug addiction who directs the Baron Edmond de Rothschild Chemical Dependency Institute at Beth Israel Medical Center in New York. Dr. Des Jarlais cited her recent widely reported study showing that cellphones alter brain metabolism as a typical example of her unusually creative scientific thinking.

Her days now veer from reviewing raw laboratory data with her research colleagues to leading the back-to-back meetings of a government functionary, but the two roles are joined by the mantra of her time at the institute: Policy should be grounded in valid science. One recent decision in the upper echelons of the National Institutes of Health reflects a similar conclusion: The drug abuse institute and the National Institute on Alcohol Abuse and Alcoholism are on track to be merged into a joint institute on addiction still in the planning stages.

Dr. Volkow says she is all for the merger, calling the current structure Òan artificial division with many missed opportunities,Ó like having an institute for every particular variety of cancer. Addictions tend to move together, she said, sharing many triggers and a great deal of biology. Again, it is all about the dopamine.

All addictive substances send dopamine levels surging in the small central zone of the brain called the nucleus accumbens, which is thought to be the main reward center. Amphetamines induce cells to release it directly; cocaine blocks its reuptake; alcohol and narcotics like morphine, heroin and many prescription pain relievers suppress nerve cells that inhibit its release. Addicts and first-time users alike get the high that correlates with the dopamine wave. Only a minority of novices, however, will develop the compulsion to keep taking the drug at great personal cost, a behavior that defines addiction.

Researchers now postulate that addiction requires two things. First is a genetic vulnerability, whose variables may include the quantity of dopamine receptors in the brain: Too few receptors and taking the drug is not particularly memorable, too many and it is actually unpleasant. Second, repeated assaults to the spectrum of circuits regulated by dopamine, involving motivation, expectation, memory and learning, among many others, appear to fundamentally alter the brainÕs workings.

Treating people with the prescription drug problems is particularly challenging, because, of course, for these particular drugs, physicians are the nationÕs pushers. The number of prescriptions written for potentially addictive pain medications has soared in the last decade, reaching more than 200 million in 2010, Dr. Volkow said. Surveys asking teenagers where they get pills find that relatively few buy from strangers. Many have their own prescriptions, often from dental work. Even more are given pills by friends and relatives, presumably out of other legitimate prescriptions.

The institute is starting a multipronged effort to teach and to learn more about pain control as it relates to addiction. New science for pain control may take some time to devise, Dr. Volkow said. One promising way to lessen the addictive properties of pain relievers, she said, is to slow the speed with which they reach the brain: A dribble of dopamine is far less addictive than a surge. New formulations to deliver pain relief slowly should minimize older drugsÕ addictive potential. Skin patches are one example of this effort (although they can still cause fatal overdoses) and research is under way into others.

Another technique is combining drugs to deter abuse. The drug suboxone, an alternative to methadone, is constructed with this intent. It combines a methadone like drug for maintaining addicts on an even keel with another drug that counteracts overdoses and opiate-associated highs. If the suboxone is taken orally, as intended, the methadone effect predominates. But all hard-core addicts know that if an oral drug is injected into the bloodstream, it will rush into the brain and create a far more dramatic high. If suboxone is injected, the second substance kicks in immediately and prevents the high. Visit the New York Times for the article.


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