G
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I nearly didn't read this but halfway through was astonished at the further scientific findings on how our brains work. This alone causes me to want a government that better supports the sciences (even if it means funding what we might term off-the-wall projects). - Perdita
New Ways to Loosen Addiction's Grip - ANAHAD O'CONNOR, NYT, August 3, 2004
When Aaron, a 33-year-old writer from New York, decided to get help for his five-year addiction to painkillers, there was really only one option. Every morning, he visited a local clinic for a small cup of methadone, the standard treatment for addiction to heroin and other opiates since the 1960's. But his life soon revolved around the clinic's hours, he said, and the daily routine was humiliating. "I had to stand in line with a bunch of people who were talking about getting high," and take a urine test for illicit drugs each week, said Aaron, who spoke on the condition that his last name be withheld.
Then, a year and a half ago, a quiet scientific advance gave Aaron—and 60,000 other Americans—a chance to break their dependence on drugs without shame. Buprenorphine, made by Reckitt Benckiser and sold under the brand name Suboxone, became the first prescription medication for people addicted to heroin or painkillers. The small orange tablet is available by prescription at any neighborhood pharmacy. It relieves symptoms of opiate withdrawal like agitation, nausea and insomnia. But unlike methadone, buprenorphine (pronounced byoo-pre-NOR-feen) is only weakly addictive, and is thus less tightly regulated. Above a certain dosage, more will not produce a high, so it has a far lower risk of overdose than methadone. And once a patient has taken a pill, the effects last for about three days, greatly decreasing the chance of a relapse.
Serious drug addiction is a problem that afflicts more than 10 million Americans. The grip of hard-core drugs like heroin and cocaine is notoriously stubborn, and relapse rates are staggering. Rehabilitation programs have only limited success. Dropout rates are high, and even many addicts who do stay in rehab slide back into using drugs periodically. But buprenorphine is the first of a new generation of prescription drugs that is changing the landscape of addiction treatment, providing new hope and moving addiction from clinics and rehab centers, long seen as magnets for junkies, pushers and gloom, into the comfort of the doctor's office.
In laboratories around the country, researchers are creating prescription medications to alleviate craving or blunt euphoria, and working on vaccines that can prevent people from getting high by mopping up a drug in the bloodstream. In some cases, the research is already bearing fruit: Campral, a new prescription drug to block cravings for alcohol, was approved by the Food and Drug Administration last week. Other medications are likely to enter the market within a few years.
At some point, experts say, the new treatments will allow addiction to be viewed—and treated—like any other chronic, relapsing disease. "There has been a revolution in the way we view addiction," said Dr. Charles A. Dackis, chief of psychiatry at the University of Pennsylvania Medical Center-Presbyterian. "It's being seen now as a disease of the reward centers of the brain, much like pneumonia is seen as a disease of the lungs."
The new treatments arrive as scientists are beginning to unravel the underlying neurobiology of drug dependence. Researchers have known for some time that all substances of abuse, including nicotine, alcohol, cocaine, marijuana and heroin, activate the same pleasure pathway in the brain. But they are now finding that many drugs cause subtle changes in brain activity that remain for weeks, months or years. Such alterations, studies have found, help unleash the cravings that can plunge recovered users back into the throes of addiction long after their last puff or snort.
"We now know the changes these drugs cause in the brain at the molecular level that lead to addiction," said Dr. Eric J. Nestler, chairman of the department of psychiatry at the University of Texas Southwestern medical center. "Because of imaging studies we know where to focus, and that's a brand new advance."
Although experts acknowledge that drug abuse begins as a voluntary behavior, many argue that at some point a perilous line is crossed. Brain cells that are repeatedly assaulted by addictive drugs change shape. The brain's reward pathway - the same, primitive system that by evolutionary design makes basic drives like sex and eating pleasurable - is hijacked. The urge to get high is insatiable. In experiments, lab animals will press a lever for cocaine until it kills them.
Each drug manipulates the reward circuitry in a different way, but in brain scans every drug lights up a link in the neural pathway called the nucleus accumbens, the universal site of addiction. After repeated bombardment by drugs, the system loses sensitivity to more natural rewards. "These drugs stimulate the reward circuitry so acutely that over time they disrupt it," said Dr. Dackis, adding that addiction is so lethal because it tricks the brain into acting as if the drugs were necessary for survival.
Over the years, chemical substitutes that mimic addictive drugs, activating the reward circuitry and reducing cravings, have had the most success in treating addiction. Methadone, a reddish liquid first used as a maintenance treatment for heroin addicts in 1964, has long been considered the gold standard. Chemically, it is not so different from heroin. It binds to the same receptors, gradually stimulating them. Patients say they experience a warm glow, though not the euphoric daze of heroin, the feeling of being wrapped in God's warmest blanket.
…
In the brain, buprenorphine pries heroin from opiate receptors, binds tightly for two or three days, then produces just enough stimulation to relieve withdrawal symptoms. It is not perfect by any means. One drawback is that for some longtime heroin users, its effects are too weak, and methadone ends up as their only alternative. But for those who can take it, buprenorphine's effects last longer than methadone's, experts say, which drives the likelihood of relapse down sharply. "If you get stressed out and decide you want to get high, you can go see your dealer but you're wasting your money because there's that three-day safety cushion where buprenorphine is blocking the receptors," Dr. McDowell said.
Last year, only 5 out of 43 patients at Dr. McDowell's center had relapsed after their first six months on buprenorphine, an 88 percent success rate; on methadone, treatment programs for most forms of drug addiction have less than a 50 percent success rate after six months, he said. In France, where buprenorphine has been on the market less than 10 years, fatal overdoses from heroin and other opiates have fallen almost 80 percent. "In the field of addiction treatment, those figures are just unbelievable," he said.
…
Perhaps buprenorphine's biggest draw, said Roberta P. Sales, a nurse coordinator at the Columbia program, is that it frees addicts from the methadone clinic. With a prescription, they can get a month's supply of the medication at the pharmacy. The cost is about $5 to $10 a day. "How can you possibly work or go to school when the primary focus of your day is going to a methadone program?" she said. "With buprenorphine, I've had patients literally break down and cry because they can travel to another state and see their family for the first time in years."
For all its promise, buprenorphine, whose use is confined to opiates, will help only a fraction of the Americans who abuse drugs. Researchers say their focus now is on finding new treatments for a wide variety of drugs. They hope to find medications that are not simply chemical substitutes but eliminate dependence altogether. In some laboratories, researchers are working on developing medications that do away with the cravings that make abstinence from any drug a struggle. "It's never as simple as just washing the drug out of your body," said Dr. Anna Rose Childress, a research associate professor of psychology at the University of Pennsylvania medical school.
The shift toward treating cravings came largely from imaging studies. Researchers found that when a recovering addict was shown slight cues or reminders of an old drug habit—an antidrug advertisement, for example, a cigarette or a syringe—it set off intense activity in the brain's reward circuitry, and produced an urge to relapse. "Often, this is what pulls people back in," Dr. Dackis said. Campral, the anticraving medication, made by Merck and approved for alcoholism by the F.D.A. last week, appears to dampen that response by elevating levels of GABA, the brain's major inhibitory neurotransmitter. Dr. Childress believes that GABA helps rein in the reward circuitry that drives people to seek drugs and other pleasurable experiences. Campral has been used in Europe for several years.
At least two other drugs that increase GABA, topiramate and baclofen, seem to curb cravings for cocaine, heroin, cigarettes and alcohol. Dr. Childress, who is involved in clinical trials of baclofen for cocaine, said the medications may even help conquer compulsive behaviors like pathological gambling and sexual compulsion. Scientists have also found that the prescription medication modafinil, used for sleep disorders, can blunt the euphoria of cocaine.
…
It may be years, experts concede, before the promise of vaccines, anticraving drugs and other new treatments can be fully realized. And if the prospect of a world without drug addiction seems too good to be true, it just might be. None of the drugs is a magic bullet. Psychotherapy will still be needed to help addicts repair frayed relationships and overcome psychological dependence. Moreover, an addict who is determined to get high, experts say, can counteract even the most effective medication - by not taking it. "In the drug abuse field you have to be humble," said Dr. Margaret Haney, a researcher at the New York State Psychiatric Institute who is involved in clinical trials of the cocaine vaccine. "There is nothing that is going to work for everyone, but we're just hoping to increase the odds that someone will be able to stay clean and have just enough time to get their lives back in order."
------------------
As most of you know, to read the full article you need to register with the NYT online, no cost and only once. url
New Ways to Loosen Addiction's Grip - ANAHAD O'CONNOR, NYT, August 3, 2004
When Aaron, a 33-year-old writer from New York, decided to get help for his five-year addiction to painkillers, there was really only one option. Every morning, he visited a local clinic for a small cup of methadone, the standard treatment for addiction to heroin and other opiates since the 1960's. But his life soon revolved around the clinic's hours, he said, and the daily routine was humiliating. "I had to stand in line with a bunch of people who were talking about getting high," and take a urine test for illicit drugs each week, said Aaron, who spoke on the condition that his last name be withheld.
Then, a year and a half ago, a quiet scientific advance gave Aaron—and 60,000 other Americans—a chance to break their dependence on drugs without shame. Buprenorphine, made by Reckitt Benckiser and sold under the brand name Suboxone, became the first prescription medication for people addicted to heroin or painkillers. The small orange tablet is available by prescription at any neighborhood pharmacy. It relieves symptoms of opiate withdrawal like agitation, nausea and insomnia. But unlike methadone, buprenorphine (pronounced byoo-pre-NOR-feen) is only weakly addictive, and is thus less tightly regulated. Above a certain dosage, more will not produce a high, so it has a far lower risk of overdose than methadone. And once a patient has taken a pill, the effects last for about three days, greatly decreasing the chance of a relapse.
Serious drug addiction is a problem that afflicts more than 10 million Americans. The grip of hard-core drugs like heroin and cocaine is notoriously stubborn, and relapse rates are staggering. Rehabilitation programs have only limited success. Dropout rates are high, and even many addicts who do stay in rehab slide back into using drugs periodically. But buprenorphine is the first of a new generation of prescription drugs that is changing the landscape of addiction treatment, providing new hope and moving addiction from clinics and rehab centers, long seen as magnets for junkies, pushers and gloom, into the comfort of the doctor's office.
In laboratories around the country, researchers are creating prescription medications to alleviate craving or blunt euphoria, and working on vaccines that can prevent people from getting high by mopping up a drug in the bloodstream. In some cases, the research is already bearing fruit: Campral, a new prescription drug to block cravings for alcohol, was approved by the Food and Drug Administration last week. Other medications are likely to enter the market within a few years.
At some point, experts say, the new treatments will allow addiction to be viewed—and treated—like any other chronic, relapsing disease. "There has been a revolution in the way we view addiction," said Dr. Charles A. Dackis, chief of psychiatry at the University of Pennsylvania Medical Center-Presbyterian. "It's being seen now as a disease of the reward centers of the brain, much like pneumonia is seen as a disease of the lungs."
The new treatments arrive as scientists are beginning to unravel the underlying neurobiology of drug dependence. Researchers have known for some time that all substances of abuse, including nicotine, alcohol, cocaine, marijuana and heroin, activate the same pleasure pathway in the brain. But they are now finding that many drugs cause subtle changes in brain activity that remain for weeks, months or years. Such alterations, studies have found, help unleash the cravings that can plunge recovered users back into the throes of addiction long after their last puff or snort.
"We now know the changes these drugs cause in the brain at the molecular level that lead to addiction," said Dr. Eric J. Nestler, chairman of the department of psychiatry at the University of Texas Southwestern medical center. "Because of imaging studies we know where to focus, and that's a brand new advance."
Although experts acknowledge that drug abuse begins as a voluntary behavior, many argue that at some point a perilous line is crossed. Brain cells that are repeatedly assaulted by addictive drugs change shape. The brain's reward pathway - the same, primitive system that by evolutionary design makes basic drives like sex and eating pleasurable - is hijacked. The urge to get high is insatiable. In experiments, lab animals will press a lever for cocaine until it kills them.
Each drug manipulates the reward circuitry in a different way, but in brain scans every drug lights up a link in the neural pathway called the nucleus accumbens, the universal site of addiction. After repeated bombardment by drugs, the system loses sensitivity to more natural rewards. "These drugs stimulate the reward circuitry so acutely that over time they disrupt it," said Dr. Dackis, adding that addiction is so lethal because it tricks the brain into acting as if the drugs were necessary for survival.
Over the years, chemical substitutes that mimic addictive drugs, activating the reward circuitry and reducing cravings, have had the most success in treating addiction. Methadone, a reddish liquid first used as a maintenance treatment for heroin addicts in 1964, has long been considered the gold standard. Chemically, it is not so different from heroin. It binds to the same receptors, gradually stimulating them. Patients say they experience a warm glow, though not the euphoric daze of heroin, the feeling of being wrapped in God's warmest blanket.
…
In the brain, buprenorphine pries heroin from opiate receptors, binds tightly for two or three days, then produces just enough stimulation to relieve withdrawal symptoms. It is not perfect by any means. One drawback is that for some longtime heroin users, its effects are too weak, and methadone ends up as their only alternative. But for those who can take it, buprenorphine's effects last longer than methadone's, experts say, which drives the likelihood of relapse down sharply. "If you get stressed out and decide you want to get high, you can go see your dealer but you're wasting your money because there's that three-day safety cushion where buprenorphine is blocking the receptors," Dr. McDowell said.
Last year, only 5 out of 43 patients at Dr. McDowell's center had relapsed after their first six months on buprenorphine, an 88 percent success rate; on methadone, treatment programs for most forms of drug addiction have less than a 50 percent success rate after six months, he said. In France, where buprenorphine has been on the market less than 10 years, fatal overdoses from heroin and other opiates have fallen almost 80 percent. "In the field of addiction treatment, those figures are just unbelievable," he said.
…
Perhaps buprenorphine's biggest draw, said Roberta P. Sales, a nurse coordinator at the Columbia program, is that it frees addicts from the methadone clinic. With a prescription, they can get a month's supply of the medication at the pharmacy. The cost is about $5 to $10 a day. "How can you possibly work or go to school when the primary focus of your day is going to a methadone program?" she said. "With buprenorphine, I've had patients literally break down and cry because they can travel to another state and see their family for the first time in years."
For all its promise, buprenorphine, whose use is confined to opiates, will help only a fraction of the Americans who abuse drugs. Researchers say their focus now is on finding new treatments for a wide variety of drugs. They hope to find medications that are not simply chemical substitutes but eliminate dependence altogether. In some laboratories, researchers are working on developing medications that do away with the cravings that make abstinence from any drug a struggle. "It's never as simple as just washing the drug out of your body," said Dr. Anna Rose Childress, a research associate professor of psychology at the University of Pennsylvania medical school.
The shift toward treating cravings came largely from imaging studies. Researchers found that when a recovering addict was shown slight cues or reminders of an old drug habit—an antidrug advertisement, for example, a cigarette or a syringe—it set off intense activity in the brain's reward circuitry, and produced an urge to relapse. "Often, this is what pulls people back in," Dr. Dackis said. Campral, the anticraving medication, made by Merck and approved for alcoholism by the F.D.A. last week, appears to dampen that response by elevating levels of GABA, the brain's major inhibitory neurotransmitter. Dr. Childress believes that GABA helps rein in the reward circuitry that drives people to seek drugs and other pleasurable experiences. Campral has been used in Europe for several years.
At least two other drugs that increase GABA, topiramate and baclofen, seem to curb cravings for cocaine, heroin, cigarettes and alcohol. Dr. Childress, who is involved in clinical trials of baclofen for cocaine, said the medications may even help conquer compulsive behaviors like pathological gambling and sexual compulsion. Scientists have also found that the prescription medication modafinil, used for sleep disorders, can blunt the euphoria of cocaine.
…
It may be years, experts concede, before the promise of vaccines, anticraving drugs and other new treatments can be fully realized. And if the prospect of a world without drug addiction seems too good to be true, it just might be. None of the drugs is a magic bullet. Psychotherapy will still be needed to help addicts repair frayed relationships and overcome psychological dependence. Moreover, an addict who is determined to get high, experts say, can counteract even the most effective medication - by not taking it. "In the drug abuse field you have to be humble," said Dr. Margaret Haney, a researcher at the New York State Psychiatric Institute who is involved in clinical trials of the cocaine vaccine. "There is nothing that is going to work for everyone, but we're just hoping to increase the odds that someone will be able to stay clean and have just enough time to get their lives back in order."
------------------
As most of you know, to read the full article you need to register with the NYT online, no cost and only once. url
