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 Health & Beauty | June 2006 
An Anti-Addiction Pill?
 Benoit Denizet-Lewis - NYTimes
Last month, the Picower Institute for Learning and Memory at the Massachusetts Institute of Technology was host to a conference about addiction for a small, invitation-only crowd of neuroscientists, clinicians and public policy makers. It was an unusual gathering. Addiction conferences are usually sober affairs, but M.I.T. offered a lavish cocktail reception (with an open bar, no less). More important, the conference was a celebration of the new ways scientists and addiction researchers are conceptualizing, and seeking to treat, addiction. While many in the treatment field have long called addiction a "disease," they've used the word in vague and metaphorical ways, meaning everything from a disease of the mind to a disease of the spirit. Many assumed that an addict suffers from a brain-chemistry problem, but scientists had not been able to peer into our heads to begin to prove it.
Now they can, using advances in brain-imaging technology. And they tend to agree on what they see, although not necessarily on how to fix it: addiction — whether to alcohol, to drugs or even to behaviors like gambling — appears to be a complicated disorder affecting brain processes responsible for motivation, decision making, pleasure seeking, inhibitory control and the way we learn and consolidate information and experiences. This new research, in turn, is fueling a vast effort by scientists and pharmaceutical companies to develop medications and vaccines to treat addiction. The National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism are studying, or financing studies on, more than 200 addiction medications.
The search for pharmacology to treat addiction is not new. The history of addiction treatment in America is rife with supposed miracle medications and "cures," most of which turned out to be useless. But there are a handful of drugs — some developed in the mid-1900's, others in the last decade or so — that are being used to help addicts quit. For heroin addiction, there's methadone and buprenorphine, both of which bind to and activate opioid receptors in the brain. Each essentially substitutes for heroin by activating the same brain receptors as the drug, but many addiction doctors prefer buprenorphine, which the Food and Drug Administration approved in 2002, because it causes less of a high and less dependence.
For alcohol, Antabuse, which makes people physically ill if they drink, has been on the market since 1948, although it isn't widely used. Addiction scientists are more hopeful about another anti-alcoholism drug, naltrexone, which was originally developed to treat opioid addiction but was approved for the treatment of alcoholism in 1994. Studies have found it can help some alcoholics abstain from or cut down on their drinking, and two pharmaceutical companies recently teamed up to produce Vivitrol, a long-acting, injectable form of naltrexone, which the F.D.A. approved in April. Some hope Vivitrol will sidestep a huge challenge facing those seeking pharmacological solutions for addiction: unless they're getting high from it, most addicts aren't model medicine takers. (Vivitrol requires a monthly shot from a doctor.)
None of the medications currently approved to treat addiction are perfect, and in many ways they are the products of some of our earlier advances in neuroscience. In the last few years, though, scientists say they've learned a staggering amount about how addiction affects the brain, and neuroscientists and other addiction researchers are eagerly testing and developing a new generation of anti-addiction medications.
"In 5 or 10 years, we will be treating addiction very differently," predicts Nora Volkow, a psychiatrist and the director of the institute on drug abuse, who attended the M.I.T. conference and presented a lecture, "Addiction: The Neurobiology of Free Will Gone Awry," in an intense and rapid-fire speaking style. (Besides being a leading American thinker about addiction, Volkow is the great-granddaughter of Leon Trotsky.) What Volkow means is that in a decade or so, we may actually start treating addiction effectively. Addiction is one of the nation's biggest public health problems, costing $524 billion (including lost wages and costs to the public health care and criminal justice systems) each year. The majority of the estimated 20 million alcoholics and drug addicts in America (and millions more compulsive gamblers, overeaters and sex addicts, if you accept an expanded understanding of addiction) never get help. Those who do often relapse repeatedly, sometimes returning to treatment centers 5, 10 or 15 times (if they don't die first). And many of those who "recover" simply trade one addiction for another — addicts call this dance "switching seats on the Titanic."
The Dopamine Connection
For much of the past two decades, Volkow and other neuroscientists exploring the physiological basis of addiction have tried to explain it by studying the brain chemical dopamine, which functions as a neurotransmitter, sending signals between cells in the brain. Dopamine affects a variety of critical functions, including learning, memory, movement, emotional response and feelings of pleasure and pain.
Dopamine was originally thought to serve as a kind of pleasure signal in the brain, telling us when something feels good or rewarding. But scientists now believe that dopamine is more a predictor of salience — that is, it tells us, and then helps us to remember, what we should focus on. When you see a person you are strongly attracted to, scientists can now see a spike of dopamine in your brain. If you are hungry and smell a food you like, dopamine also increases. But even unpleasant experiences — like physical pain or the fear of an intruder in the house — can cause a dopamine spike. (Some hypothesize that different dopamine receptor cells are responsible for firing during rewarding or aversive situations.)
Drugs, particularly cocaine and methamphetamines, cause a large increase in the amount of dopamine secreted and pooling between brain cells, leading to feelings of euphoria. With regular, repeated "addictive" drug use, though, the brain eventually responds by reducing its normal release of dopamine. Studies also show a simultaneous decrease in the number of dopamine receptors created. That, in turn, makes the brain's reward system less likely to respond to behaviors (romance, a good meal, the company of friends) that produce a normal dopamine surge. The addicted brain essentially becomes pathologically selective, dependent on bigger and bigger blasts of, say, cocaine to feel rewarded.
Perhaps most fascinating to addiction researchers is how an increase in dopamine creates a craving — and an expectation of a reward. In a study published earlier this month in The Journal of Neuroscience, Volkow used a brain scan to look at the dopamine releases in 18 cocaine addicts while they watched two videos: one of nature scenes, the other of people using cocaine. Volkow found that dopamine increased while the addicts watched the cocaine video and that the severity of the increase matched their self-reported level of craving for the drug. "For these people, their lives and experience had taught them that when they see others using cocaine, they're probably about to get rewarded with drugs, too," Volkow told me. "So even though they consciously knew that they weren't going to get cocaine after watching the video, their brains had learned to expect the reward."
Scientists posit that cue-induced dopamine spikes and craving essentially overpower the brain's well-meaning frontal cortex, which is responsible for planning and decision making. The institute on drug abuse is currently financing studies of medications that could potentially blunt that process, interfering with the release of dopamine when an addict sees a conditioned cue.
Dopamine also travels to the parts of the brain responsible for solidifying memory, like the amygdala, which learns and stores emotional memories (including the high of drugs). Some researchers hypothesize that through a combination of medicine and behavioral therapy, addicts could "unlearn" these powerful memories and associations, making them less likely to relapse when they see a cue. "Potentially, you could put an addict in a virtual-reality situation where you show them videotapes of friends they used to use drugs with, or whatever their strongest triggers are," Eric Nestler, a neuroscientist and addiction specialist at the University of Texas Southwestern Medical Center, told me earlier this month. "But now, the cue isn't associated with any kind of rewarding response. So then you can give a medication, which we're making progress on developing, that enhances memory formation. Essentially, you'd be teaching them something new — that a line of white powder means nothing special." |
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