My name is James. For a species wired for survival, we have an odd habit of getting hooked on things that can kill us. New research is revealing why--- and opening the door to the long-dreamed-of cure. By Michael D. Lemonick, With Alice Park.
I was driving up the Massachussetts Turnpike one evening last Febuary when I knocked over a bottle of water. I grabbed for it, swerved inadvertently---and a few seconds later found myselfblinking into the flashlight beam of a state trooper. " How much have you had to drink tonight, sir?" he demanded. Before I could help myself, I blurted out an answer that surely a new one to him. "I haven't had a drink ," I said indignantly,"since 1981."
It was both perfectly true and very pertinent to the trip I was making. By the time I reached my late 20s, I'd poured down as much alcohol as normal people consume in a lifetime and plenty of drugs---mostly pot---as well. I was, by any reasonable measure, an active alcoholic. Fortunately, with a lot of help, I was able to stop. And now I was on my way to Mclean Hospital in Belmont, Mass., to have my brain scanned in a functional magnetic-resonance imager (fmri). The idea was to see what the inside of my head looked like after more than a quarter-century on the wagon.
Back when I stopped drinking, such an experiment would have been unimaginable. At the time,the medical establishment had come to accept the idea that alcoholism was a disease rather than a moral failing; the American Medical Association(AMA)had said so in 1950. But while it had all the hallmarkes of a desease, including specific symptoms and a perdictable course, leading to disability or even death,alcoholism was different. Its physical basis was a complete mystery---and since nobody forced alcoholicsto drink, it was still seen, no matter what the AMA said is somehow voluntary. Treatment consisted mostly of talk therapy, maybe some vitamins and usually a strong recommendation to join Alcoholics Anonymous. Although it's a totally nonprofessional organization, founded in 1935 by ex-drunk and active drinker, AA has managed to get millions of people off the bottle, using group support and a program of accumulated folk wisdom.
While AA is astonishingly effective for some people, it doesn't work for everyone; studies suggest it succeeds about 20% of the time, and other forms of treatment, includeing various types of behavioral therapy, do no better. The rate is much the same with drug addiction,which experts see as the same disorder triggered by a different chemical. "The sad part is that if you look at where addiction treatment was 10 years ago, it hasn't got much better," says Dr. Martin Paulus, a proffessor of psychiatry at the University of California at San Diego. "You have a better chance to do well after many types of cancer than you have of recovering from methamphetemine dependence"
That could all be about to change. During those same 10 years,researchers have made extraordinary progress in understanding the physical basis of addiction. They know now,for example,that 20% success rate can shoot up to 40% if treatment is ongoing(very much the AA model, which is most effective when members continue to attend meetings long after their last drink). Armed with an array of increasingly sophisticated technology ,including fmris and pet scans,investigators have begun to figure out exactly what goes wrong in the brain of an addict---which neurotransmitting chemicals are out of balance and what regions of the brain are affected. They are developing a more detailed understanding of how deeply and completely addiction can effect the brain, by hijacking memorymaking processes and by exploiting emotions. Using that knowledge,they've begun to design new drugs that are showing promise in cutting off the craving that drives an addict irresistibly toward relapse---the greatest risk facing even the most dedicated abstainer.
"Addictions," says Joseph Frascella,director of the division of clinical neuroscience at the National Institute on Drug Abuse(nida),"are repettitive behaviors in the face of negative consequences,the desire to continue something you kmow is bad for you."
Addiction is such a harmful behavior,in fact,that evolution should have long ago weeded it out of population:if it's hard to drive safely under the influence,imagine trying to run from a saber-tooth tiger or catch a squirrel for lunch. And yet, says Dr. Nora Volkow,director of nida and a pioneer in the use of imaging to understand addiction, "the use of drugs has been recorded since the biginning of civilization. Humans in my view will always want to experiment with things to make them feel good."
That's because, drugs of abuse co-opt the very brain function that allowed our distant ancestors to survive in a hostile world. Our minds are programmed to pay extra attention to what neurologist call salience---that is, special relevance. Threats, for example, are highly salient,which is why we instinctively try to get away from them. But so are food and sex because they help the individual and the species survive.Drugs of abuse capitalize on this ready-made programming . When exposed to drugs, our memory system, reward circuits, decisionmaking skills and conditioning kick in---salience in overdrive---to create an all consuming pattern of uncontrollable craving. "Some people have a genetic predisposition to addiction,"says Volkow."But because it involves these basic brain functions, everyone will become an addict if sufficiently exposed to drugs or alcohol."
That can go for nonchemical addictions as well. Behaviors, from gambling to shoping to sex, may start out as habits but slide into addiction. Sometimes there might be a behavior-specific root of the problem. Volkow's research group, for example, has shown that pathologically obese people who are compulsive eaters exhibit hyperactivity in the areas of the brain that process food stimuli--- including the mouth, lips and tongue. For them, activating these regions is like opening the floodgates to the pleasure center. Almost anything deeply enjoyable can turn into an addiction,though.
Of course, not everyone becomes an addict. That's because we have other, more analyical regions that can evaluate consequences and override mere pleasure seeking brain imaging is showing exactly how that happens. Paulus, for example, looked at mathamphetamine addicts enrolled in a VA hospital's intensive four-week rehabilitation program. Those who were more likely to relapse in the first year after completing the program were also less able to complete tasks involving cognitive skills and less able to adjust to new rules quickly. This suggested that those patients might also be less adept at using analytical areas of the brain while performing decision-making tasks. Sure enough, brain scans showed that there were reduced levels of activation in the prefrontal cortex, where rational thoughts can override impulsive behavior. It's impossible to say if the drugs might have damaged these abilities in the relapsers---an effect rather than a cause of the chemical abuse---but the fact that the cognitive deficit existed in only some of the meth users suggests that there was something innate that was unique to them. To his surprise, Paulus found that 80% to 90% of the time, he could Pingatesaccurately predict who would relapse within a year simply by examining the scans. Another area of focus for researchers involves the brain's reward system, powerd largely by the neurotransmitter dopamine. investigators are looking specifically at the family of dopamine receptors that populate nerve cells and bind to the compound. The hope is that if you can dampen the effect of the brain chemical that carries the pleasurable signal,you can loosen the drug hold. One particular group of dopamine receptors,for example called D3,seems to multiply in the presence of cocaine,mathamphetamine and nicotine,making it possible for more of the drug to enter and activate nerve cells. "Receptors density is thought to be an amplifer," says Frank Vocci,director of
macotherapies at NIDA. "(Chemically) blocking D3 interrupts an awful lot of drugs' effects. It is probably the the hottest target in modulating the reward system." But just as there are two ways to stop aspeeding car-by easing off the gas or hitting the brake pedal-there are two different possibilities for muting addiction. If dopamine receptors are the gas, the brain's own inhibitory systems act as the brakes. In adddicts, this natural damping circuit, called GABA (gamma-aminobutyric acid), appears to be faulty. Without a proper chemical check on excitatory messages set off by drugs, the brain never appreciates that it's been satiated.
As turnes out, vigabatrin, an antiepilepsy treatment that is marketed 60 countries (but not yet in the U.S.), is an effective GABA booster. In epileptics, vigabartin suppresses overactivated motor neurons that cause muscles to contract and go into spasms. Hoping that enhancing GABA in the brains of addicts could help them control thier drug cravings, two biotech companies in the U.S., Ovation Pharmaceuticals and Catalyst Pharmaceuticals, are studying the drug's effect on methamphetamine and cocaine use. So far, in animals, vigabatrin prevents the breakdown of GABA so that more of the inhibitory compound can be stored in hole form in nerve cells. That way, more of it could be released when those cells are activated by a hit from a drug. Says Vocci, optimistically:"If it works, it will proably work on all addictions."
hottest target in modulating the reward system."
