VACCINES TO COMBAT DRUG ADDICTION SHOWING PROMISE

Vaccines to help people recover from such addictions as nicotine,
cocaine, heroin and methamphetamines now appear scientifically and
medically achievable after doctors reported Monday that a vaccine to
treat cocaine dependence had produced a large enough antibody
response to reduce cocaine use in 38% of addicted individuals.

Those results come on the heels of last week's announcement that the
federal government would fund a large clinical trial of a nicotine
vaccine based on earlier promising studies.

Neither the nicotine nor the cocaine vaccine prevents addiction the
way traditional vaccines prevent diseases, nor do similar vaccines in
development.

Instead the products are designed for use with other treatments, such
as behavioral therapy, to help people kick the habit.

They work by stimulating the body's immune system to create
antibodies that bind to the drug and prevent it from reaching the
brain and producing a chemical high.

"Fifteen years ago, people thought this was completely stupid," said
Dr. Thomas R. Kosten, a psychiatrist at Baylor College of Medicine in
Houston and senior author of the cocaine study.

But a series of technological advances has changed that, he said.

"This is trying to come out and attack drug abuse in a different
manner," said Kim D. Janda, a professor of chemistry and immunology
who works on vaccines at the Scripps Research Institute in La Jolla.
"The National Institutes of Health has spent hundreds of millions of
dollars to develop drug treatments, and they haven't gone anywhere.
They have to see this is a better way."

But even as recent scientific developments highlight the promise of
such vaccines, the hurdles to getting such addiction-battling drugs
to consumers are revealed. Legal and financial barriers may prevent
all but a nicotine vaccine from reaching the market in the near future.

"It's very worthy science, and we have to move it forward," Janda
said. "Addiction tears at the fabric of society. Families are ruined.
But that doesn't translate into dollars in pharmaceutical companies' pockets."

Drugs like cocaine and nicotine are comprised of tiny molecules that
are too small for the immune system to recognize, allowing them to
slip through the body's blood-brain barrier. Researchers realized
they could circumvent that problem by tethering drug molecules to
larger proteins that the body recognizes as foreign. Then the immune
system would mount a defense against both.

"You have to trick the body into making an antibody response to this
small molecule," said Berma M. Kinsey, a research chemist at Baylor
who works on cocaine vaccines.

Vaccines against nicotine and cocaine are the most advanced, but
versions to block the effects of methamphetaimine, heroin and
phencyclidine, or PCP, are also in development.

"It's like a sponge for that specific drug," Janda said. "But a
problem is some people respond very well and some don't."

Further, such vaccines address only the chemical addiction of drug
abuse, not the behavioral aspects.

For example, NicVAX, the nicotine vaccine that got a $10-million
grant last week from the National Institute on Drug Abuse, can block
the release of dopamine in a smoker's brain.

"But unless you are interested in stopping smoking, the habit
continues," said biochemist Raafat Fahim, chief executive of Nabi
Biopharmaceuticals in Rockville, Md., which makes NicVax.

In the new cocaine study, researchers enrolled 115 cocaine-dependent
people in a 24-week trial. The participants were also addicted to
opioids and were enrolled in a methadone treatment program, which
made it easier for researchers to retain the subjects long enough to
test the vaccine.

Half of the individuals received five injections of the vaccine over
12 weeks, and the other half received placebo injections. The
participants' urine was tested three times per week.

Of the 55 people who received all five vaccine injections, 38%
attained cocaine antibody levels of 43 micrograms per milliliter or
higher, which previous research indicates is necessary to blunt the
cocaine response. Those individuals had significantly more
cocaine-free urine samples between weeks nine and 16 than individuals
who did not achieve sufficient antibody levels or who received
placebo injections.

Among high-antibody producers, 53% were abstinent from cocaine more
than half the time, compared with 23% of people who made lower levels
of antibodies.

No serious side effects were reported. The study was published in the
Archives of General Psychiatry.

The antibodies eventually subside over a period of weeks, so booster
shots would be required, and more work is needed to improve the
response rate, Kosten said.

"This is a first-generation vaccine, and we wanted something simple
and safe to show it works," he said.

The National Institute on Drug Abuse will fund a larger study of the
cocaine vaccine beginning in January.

People who want to quit smoking already have several behavioral and
pharmaceutical treatments to choose from, but there are no medical
treatments for cocaine use, methamphetamine or PCP dependence.
Methadone is only modestly effective in treating heroin addiction.

However, need and desire may not be enough to move vaccine technology
to the market.

"Drug manufacturers shy away from addiction treatments due to
liability," Kosten said. "They are afraid that if someone has an
overdose later, they would blame it on what the vaccine did to their
body. We have people lining up and down the street to take the
vaccine. It's almost a no-brainer. The problem is we have to get by
this huge legal barrier."

The vaccine approach won't work to treat alcohol addiction because
alcohol molecules are simply too small and shapeless to tether to
larger proteins, said Baylor's Kinsey.

It's also not likely to work for marijuana because the active
chemical -- THC -- is extremely sensitive to light, air, heat and
acid, all of which makes it difficult to manipulate in the
laboratory, she said.