New Ways to Loosen Addiction's Grip -- NYTimes
From: David James Polewka (joseywales_at_outlaw.nospam)
Date: 08/03/04
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Date: Tue, 03 Aug 2004 14:45:33 GMT
New Ways to Loosen Addiction's Grip
By ANAHAD O'CONNOR
Published: 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 its time, methadone was considered a breakthrough: It got people off
heroin, reduced fatal overdoses and slowed the spread of infectious
diseases through dirty needles. But it became clear that methadone had
its own problems. Like heroin, it was strongly addictive. It was
classified by the Drug Enforcement Administration as a Schedule 2 drug,
in the same category as cocaine and PCP. And by law, it had to be
distributed by special clinics that were so bathed in stigma that
several states banned them. Former Mayor Rudolph W. Giuliani of New York
declared five years ago, when he was in office, that methadone programs
encouraged people to trade one addiction for another, and should be shut
down.
Between 180,000 and 200,000 Americans are on methadone, said Dr. David
M. McDowell, director of a program at Columbia University that helps
people make the transition from methadone to buprenorphine, then refers
them to other doctors for private care. In New York, 36,000 people are
on methadone.
"The most stigmatized thing in this world is methadone," said Dr. Edwin
A. Salsitz, director of Beth Israel Medical Center's methadone program
in New York. "There is nothing people try to hide more than being on
methadone. They don't want to be seen going into a clinic. They won't
tell anyone they're taking it."
Methadone's limitations prompted experts to look for medications that
were less likely to place recovering addicts in a stranglehold. What
they found was buprenorphine. Like methadone, it is a chemical
substitute for heroin. But it activates receptors so weakly that it has
a better safety profile and many users can be slowly weaned from it,
leaving them drug-free.
"Buprenorphine is the most important advance certainly in heroin and
opiate treatment if not all addiction treatments in the last 30 years,"
said Dr. Alan I. Leshner, a former director of the National Institutes
of Drug Abuse.
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.
Doctors in the United States wrote 80,000 prescriptions for
buprenorphine in 2003, a number that is expected to soar in the coming
years. Lured by the prospect of privacy, many heroin and opiate abusers
are seeking help for the first time. Others are switching from
methadone.
Dr. Chadd A. Herrmann, a psychiatrist in Manhattan, said he has received
about 20 telephone calls in the last three weeks from people looking for
buprenorphine. He had to turn them away, he said, because he was still
awaiting authorization to prescribe it. In New York, doctors who want to
prescribe buprenorphine are required to take an eight-hour training
course and then receive approval from the state.
Dr. Herrmann, whose practice is on Fifth Avenue, said many of the people
who called did so "because of my address." He added, "They make it
really clear that they don't want to be in a program or clinic in some
other part of the city."
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.
Still other scientists are trying to solve two problems common among
substance abusers: They often forget to take their medications, and even
those who stay in recovery end up "slipping" periodically.
Vaccines, some researchers believe, may provide answers to these
problems.
At Yale and Columbia, for example, researchers are testing a vaccine
that uses molecules of cocaine bound to harmless pathogens. When the
vaccine is injected into the body, the immune system responds by
producing antibodies to the cocaine and to the pathogen it is paired
with. After a handful of immunizations over the course of three months,
the user has enough antibodies to prevent at least three times the
typical dose of cocaine from reaching the brain.
"The people that make significant amounts of antibodies say that cocaine
isn't what it used to be, and the people who make the highest levels of
antibodies stop using it altogether," said Dr. Thomas Kosten, a
professor of psychiatry and medicine at the Yale medical school.
In Australia, scientists are experimenting with a similar vaccine that
blocks nicotine.
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.
=========================
"Endeavor to persevere"
=========================
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