PROMISING MEDICATIONS LEND HOPE TO ADDICTS SEEKING TREATMENT

ST. LOUIS - At his lowest point, Steve Duffie was popping pills and
shooting heroin up to 10 times a day. Then he started taking a drug to stop.

Since February, he has been traveling three times a week to south St.
Louis, where a staff person at Assisted Recovery Centers of America watches
him swallow pills containing naltrexone.

"I feel a lot better," said Duffie, 24, who has stayed drug free. "I feel
better about myself and the life I'm living now."

Naltrexone has been around for 20 years, but few people know about it.

Experts say a major shift in thinking about how alcohol and drugs impact
the brain is producing more and better medications to treat addiction to
drugs and alcohol.

"Based upon an accumulation of research findings, our ideas about what
alcohol dependence is, when it starts and how to treat it are changing
rapidly," Dr. Mark Willenbring of the National Institute on Alcohol Abuse
and Alcoholism told a recent American Medical Association briefing. "New
tools are becoming available, and treatment outcomes, while perhaps better
than most people think, are likely to significantly improve in the next
decade if we can get these treatments to the people who need them."

Research into medications to treat addiction has taken off.

Twelve years ago, the federal government was funding just a half-dozen
clinical trials of drugs for alcoholism, and no pharmaceutical company was
conducting research. Today, the government is financing studies of 51
drugs, and nine companies are doing clinical trials.

Like antidepressant medication, some of the newer drugs are designed to
repair chemical unbalances and abnormalities in the brain that occur as a
result of chronic abuse, Willenbring said.

Promising medications include brand new drugs and those already approved
for other purposes. Among them:

Topiramate - approved to treat epilepsy - for alcoholism and cocaine addiction.

Baclofen - approved for muscle tightness, cramping and spasms - for alcoholism.

Ondansetron - to treat nausea and vomiting - for alcoholism.

Nalmefene - approved in 1994 for alcoholism - is being developed as a
six-month implant for both alcoholism and opiate addiction.

Federal health officials held a forum July 29 at St. Louis University, part
of a four-city stop, to raise awareness among doctors and the public about
one medication, buprenorphine. Marketed under the trade names Suboxone and
Subutex, it went on the market in 2003 to treat heroin, prescription
painkiller and other opiate addictions.

Like naltrexone, it can be prescribed by private-practice physicians, so
"hopefully it will allow addiction treatment to be incorporated into
mainstream medical practice," said Nick Reuter, senior public-health
advisor at the U.S. Substance Abuse and Mental Health Services Administration.

Finding new medications for alcoholism has been challenging because
different regions of the brain are involved. That complexity also "opens up
many strategies for treatment," said Dr. Raye Litten, associate director of
the division of clinical and recovery research at National Institute on
Alcohol Abuse and Alcoholism.

Naltrexone was approved by the FDA in 1984 to treat opiate addiction, and
in 1994 to treat alcoholism. It also is being studied for use in
combination with acamprosate, the latest anti-addiction drug to gain FDA
clearance. Sold under the trade name Campral, acamprosate went on the
market in January.

An injectable form of naltrexone, Vivitrex, is currently undergoing review
by the FDA as a monthly shot.

Down the road, people might take two or three medications that act on
specific parts of the brain, experts say. The drug combinations would work
much like those designed for people with AIDS, cancer, diabetes,
depression, heart disease and high blood pressure.

"Just getting them out on the market would give patients a menu of
medications to choose from," Litten said. "Like antidepressants, if one
doesn't work, you could try another one."

Researchers are learning that many alcoholics and drug addicts need ongoing
or intermittent care much like people with other chronic conditions.
"Treatment should not be a one-time thing," said Willenbring, a
psychiatrist who directs the division of treatment and recovery research at
the federal health agency.

Treatment professionals caution that a commitment to abstinence is essential.

"You can't put this into somebody's coffee everyday and expect them to be
transformed," said Barbara Mason, a consultant to Forest Laboratories,
Inc., the company that makes Campral. "It's another tool in the toolbox of
recovery."

Yet, for all the excitement about pharmaceutical treatments, naltrexone and
acamprosate are largely going unused.

Only about 5 percent of people dependent on alcohol have ever been
prescribed medication, Willenbring said.

Fewer than 3 percent of the nation's 1.1 million opiate addicts have tried
naltrexone, even though it's been around for 20 years.

The reasons vary - from low awareness of the medications to lack of drug
coverage and a bias against taking a drug to beat an addiction.

"Most people think addicts just need to learn how to change their
behavior," said Dr. David Gastfriend, an associate professor of psychiatry
at Harvard Medical School. "That's like fighting this disease with one hand
tied behind your back."

Naltrexone works by occupying the opiate receptors in the brain. As a
result, the feel-good chemicals triggered by alcohol and opiate drugs are
blocked, eliminating the high. The brain chemicals are endorphin, dopamine,
serotonin and gamma-amino butyric acid, or GABA. The active ingredient of
naltrexone is made in St. Louis by Tyco Healthcare/Mallinckrodt, the
biggest U.S. manufacturer of the drug.

Studies have found that people who are genetically predisposed to addiction
have lower levels of endorphin in their brains but experience an excessive
release of the chemicals when they drink or do drugs, well beyond what the
average person experiences. Repeated heavy drinkers and drug users build up
a tolerance and require more and more to get high.

Eventually, alcohol or drugs are taken to relieve the unpleasant effects of
not using, such as irritability, anxiety and craving. "You're drinking to
feel normal," said Barbara Mason, co-director of the Pearson Center for
Alcoholism and Addiction Research at the Scripps Research Institute in
California.

Since naltrexone blocks the release of endorphins, if an alcoholic drinks,
speech might become slurred or walking might get wobbly, but there's no
buzz. If the person relapses on the medication, he or she is more likely to
stop after two or three drinks because the reward of feeling good has been
taken away.

After using naltrexone for several months, some alcoholics are able to
abstain from alcohol forever. Some treatment professionals describe the
drug as a "chemical chastity belt."

Acute withdrawal from alcohol and drugs can last up to seven days.
Alcoholics and addicts typically go through a protracted withdrawal that
lasts up to 30 weeks, which can include overwhelming feelings of craving,
said Percy Menzies, a pharmacist who is president of Assisted Recovery
Centers of America.

Naltrexone acts like a "helmet on the brain that protects you if you fall,"
Menzies said.

About 22 million people abuse or are addicted to drugs, according to
government statistics. That figure includes alcohol and prescription drugs.

"We have a serious drug-abuse problem in this country, including with
alcohol, even if we don't recognize it," said Dan Duncan, director of
community services at the National Council on Alcoholism and Drug Abuse,
St. Louis area. "We have a lot of stereotyping going on, people want to
think it's an inner-city problem. That's not true. Go to west county.
They're doing drugs and have the means and resources to buy whatever they
want. It costs all of us and we're affected directly or indirectly by this
problem."

Alcoholism is a disease of behavior, spirit and the brain, Mason said.
"There are therapies that deal with each aspect of the disease. AA is a
spiritually-based fellowship. There are alcohol-specific types of
counseling. But the brain has been largely ignored in recovery. Campral is
the very first drug that addresses the underlying brain aspect of the
disease and helps to restore that piece to normal."

Naltrexone doesn't repair anything in the brain; it keeps people from
getting high and eases withdrawal. Campral, or acamprosate, works differently.

Alcohol overstimulates the glutamate system, causing it to react like a car
that's idling too fast, Mason said. The abnormality can continue as long as
a year after the last drink in some alcoholics. Acamprosate regulates the
chemical activity in the glutamate region.

Campral is shipped to pharmacies across the country from Forest
Laboratories' national distribution center in St. Louis.

Other drugs used to treat addiction are methadone and disulfiram. Methadone
is an opiate given in small doses to prevent the effects of withdrawal from
drugs such as heroin. The narcotic is designed to block the high and reduce
craving. Disulfiram, which is sold under the trade name Antabuse, has been
used to treat alcoholism since 1949. Drinking while on the drug makes a
person violently ill with nausea, vomiting, heart palpitations and other
symptoms.

The aim of researchers is to design newer drugs that don't make people sick
and are not habit-forming or mood-altering. The side-effects of naltrexone
and acamprosate are generally mild, if any. They are not addictive and
don't produce a high. The drugs usually are prescribed from three months to
a year.

Research on naltrexone, disulfiram and acamprosate is uncovering other
benefits.

It appears that disulfiram helps cocaine addicts. People with a family
history of alcoholism appear to do better on naltrexone. And while
acamprosate doesn't appear to have a gender effect, one study on the
naltrexone monthly shot reported that it seemed to work better in men.

Jim Selby keeps a bottle of naltrexone on the kitchen counter as an
insurance policy.

A leg injury led to his five-year prescription drug habit. "Before I knew
it I was taking it all the time," said Selby, 47. "That's the way I was
getting by. They had complete control over my life."

He credits his turnaround to his mother, Patricia Selby, who worked many
years for the Al-Anon Information Center in St. Louis. She directed him to
Assisted Recovery Centers of America. He has been drug-free for two years.

Menzies often keeps the pills of patients who haven't been abstinent as
long as Selby at his clinic so he can monitor whether they are taking them.
Patients are advised to attend frequent group therapy sessions and to phone
regularly.

"The more contact, the better the outcome," Menzies said.

Dr. Robert Swift is a professor of psychiatry and human behavior at Brown
University. "The medications that we have are effective but not as
effective as we would like them to be," he said. "Not all people are helped
and the cure rate is not 100 percent. These medications need to be used in
the context of counseling and psychosocial treatment."

Addiction impairs motivation, so getting people to take their pills every
day can be a formidable task, said Gastfriend, who's vice president of
medical affairs at Alkermes Inc., the company seeking approval of the
monthly shot.

Vivitrex could make it easier to stay on the medication.

"By extending the action for 30 days, if they come in one day for
medication, they don't have to be motivated to come in the other 29 days,"
Gastfriend said.

Buprenorphine is used as a replacement drug for heroin, painkillers and
other opiates. Subutex is the pure form. Suboxone is a combination tablet
of buprenorphine and naloxone. Naloxone was added to prevent addicts from
grinding and injecting the tablets to get high.

The benefit of buprenorphine is that it may be easier to quit that street
drugs or prescription medicines.

In a phone interview, Dr. Clifford Bernstein, an addiction specialist, says
he has seen an increase in the number of people who've become addicted to
it. An informational booklet from the manufacturer warns that patients can
become physically dependent.

"Patients need to be educated that it's a replacement therapy which is half
opiate in composition," Bernstein said. But at the St. Louis University
forum, Theodore Cicero said research at Washington University in St. Louis
suggests that buprenorphine is a safe alternative that has less potential
for abuse than opiates. Cicero is vice chancellor for research at the
university.

Steve Duffie was prescribed Suboxone for two weeks. Then he was switched to
naltrexone. His mother, Cathy Duffie, is convinced he would have died
without the medications.

"It's amazing what addiction can do to you," she said, glancing at the son
she never gave up on. "It's a horrible life."