FIGHTING DRUGS WITH DRUGS IS LATEST ADDICTION THERAPY

PHILADELPHIA - The weapon of the future in the war on drugs will likely be
.. drugs.

Researchers are optimistic about a host of new medications that target the
chemical cycle of addiction. Some block the intense pleasure that makes
drugs such as heroin so seductive while others calm the brain during
withdrawal.

Long-acting versions of two drugs already approved - naltrexone for heroin
addicts and alcoholics, and buprenorphine for opiate addicts - are on the
horizon. They should combat one of the biggest treatment problems: Addicts
often dislike taking anything that prevents getting high.

Other researchers are taking a different tack, testing vaccines that teach
the body to treat illicit drugs like invading microbes.

Addiction experts say that advances in brain science, especially brain
imaging, have led to the testing of more promising medications than ever
before. Plus, this exploding scientific knowledge is revealing ever more
targets for future medicines.

"I think there are a lot of opportunities to develop new drugs," said Raye
Litten, coleader of the medications development team at the National
Institute on Alcohol Abuse and Alcoholism.

It remains to be seen how many medicines under scrutiny - several are
already approved for other uses - will work against addiction long term.
None is a cure.

If they work, though, experts say the country is ill-prepared to use them.
Many treatment programs have a drug-free agenda that predates effective
medications. Most do not have doctors.

Experts say no medicine is a substitute for the therapy and self-help
groups that constitute most treatment now.

Nationally, 12.4 million people are addicted to alcohol, cocaine,
stimulants such as methamphetamine, marijuana, heroin and other opioids.
About 35.7 million are addicted to nicotine.

In the last three years, two new medications joined the small band of
addiction drugs. The Food and Drug Administration approved buprenorphine, a
relatively mild narcotic, for opioid addiction in 2002. The drug can be
prescribed by community doctors, but they can treat only 30 patients at a
time, and many have waiting lists.

Last month, pharmacies received their first shipments of acamprosate
(Campral), the first new drug for alcoholism since naltrexone.

When alcoholics quit drinking, their brains can malfunction chemically for
as long as a year, said researcher Barbara Mason of the Scripps Research
Institute in California, who helped test the drug. Campral, she said, helps
restore balance.

In recent years, scientists have come to see addiction as a cycle of reward
and craving that transcends particular substances. As a result, researchers
are realizing that medications may work for more than one kind of addiction.

Addictive substances tend to affect the same parts of the brain and disrupt
the same neurotransmitters: dopamine, GABA and glutamate, said psychiatrist
Charles Dackis of the University of Pennsylvania's Treatment Research Center.

Dopamine, a neurotransmitter involved in feeling pleasure, is a key player.
It's nature's way of rewarding animals for behavior that increases odds of
survival, activities such as sex, hunting and eating. Addictive drugs tap
into the dopamine system and flood the brain with this substance in a way
that no natural activity can. That pleasure can be irresistible. "All lab
animals will self-administer cocaine to death," Dackis said.

GABA and glutamate help to regulate dopamine. GABA inhibits it. Glutamate
drives it.

Both are involved in craving, the main reason that addicts backslide so
frequently. Just the sight of something addicts link to drugs - money, a
drinking buddy, a hypodermic needle - can trigger powerful brain changes,
Dackis said. Imaging shows the response is the same as nonaddicts have when
they see sexually explicit movies.

Over time, Dackis said, addiction causes brain changes that make quitting
harder. The dopamine system gets off-kilter, and normally pleasurable
activities don't feel as good.

Also, many drugs, especially stimulants, impair the prefrontal cortex. The
seat of rational thinking, it regulates the nucleus accumbens, which Dackis
called "the universal addiction site."

All these aspects of addiction suggest possible targets for anti-addiction
drugs.

Researchers also are paying more attention to genes. Not everyone who tries
an addictive drug becomes dependent, partly because of heredity. Even
addicts can be quite different.

In the future, experts said, doctors may target specific drugs to specific
addicts. For example, preliminary research suggests that Antabuse, a
medicine that makes drinkers sick, may help nondrinking cocaine addicts.
Naltrexone may work best in another subset of hereditary alcoholics who
feel high when they drink rather than sedated, said Charles O'Brien, a Penn
addictions expert.

John Bauhs, a 41-year-old Washington alcoholic with alcoholism on both
sides of his family, joined a Penn study aimed at sorting out who responds
to naltrexone. Bauhs has been sober for seven months since starting
naltrexone. His previous record: six weeks.

The drug is "amazing," he said. "What it does is take away the urge and the
benefit of alcohol."

Even with the new medications, many patients go back to using. Boasting
abstinence rates two to three times the unmedicated norm, Campral was good
enough to get FDA approval. But at three months, just 38 percent of
patients on the drug had managed not to drink at all.

Modafinil, one of several drugs being studied for cocaine addiction, helped
a third of patients stay off cocaine for three weeks, compared with 13
percent of patients on placebo.

Experts are optimistic that better medicines will come. Meanwhile, they
said, the fact that the medicines don't cure addiction is no reason to
reject them.

"Does insulin cure diabetes?" asked Herbert Kleber, a Columbia University
psychiatrist and addictions expert. "Does any drug cure schizophrenia?"

Addiction experts say the country's primary-care doctors and drug treatment
centers will have to change to make best use of the new medicines. Few
treatment programs employ doctors, and few community doctors know enough
about addiction medicines to feel comfortable prescribing them, the experts
said.

"They're divorced worlds," said Tom McLellan, director of Penn's Treatment
Research Institute.

The country needs more addiction medicine specialists because of the new
drugs and the growing recognition that many addicts need psychiatric
medications, said H. Westley Clark, director of the Substance Abuse and
Mental Health Services Administration's Center for Substance Abuse Treatment.

Bauhs is an example of how rarely doctors think of using drugs for
addiction. He has tried more than a dozen treatment regimens. No one ever
told him about naltrexone, a drug approved for alcoholism in 1995. He
discovered Penn's naltrexone study on the Internet.

"What amazes me is that it's not more readily known or available," he said.