GETTING PAID TO USE HEROIN? PROJECT SEEKS ADDICTION CURE

NEW YORK - Taking a bold approach to addiction, researchers at Columbia
University are offering free heroin to addicts and paying them to use it
under a federally authorized program aimed at finding a cure for their drug
habits.

Two trials involving heroin injections are among six related drug-addiction
studies being conducted at Columbia's College of Physicians and Surgeons,
all of which focus on the role existing medications can play in defeating
drug addictions.

Since September, 14 addicts have received regular doses of pure heroin
after being given naltrexone, buprenorphine or methadone, which are
medications found to be effective in neutralizing heroin's high.

The researchers want to learn whether stronger doses of these medications
are needed and can be prescribed without risk, particularly in light of the
increasingly pure heroin being sold on the streets.

"A dose that was probably good enough 15 years ago may not be good enough
for heroin now," said Dr. Herbert D. Kleber, a professor of psychiatry at
Columbia who directs the medical college's division on substance abuse and
is medical director of the National Center on Addiction and Substance Abuse
at Columbia.

Heroin and cocaine have been tested on mice and other laboratory animals.
But Columbia's study is now the only one in the country testing addicts
with heroin, although researchers at Harvard have done so and researchers
at Johns Hopkins plan to.

"If you have a promising drug in animal trials," Kleber said, "you need to
do it in human trials to see if it adequately works, because we're
different from animals in physiology, metabolism and the ability to report
on subjective effects" of drugs like heroin.

Dr. Marian W. Fischman, a psychologist at Columbia who studies medications
for drug abusers, said the volunteers, who agree to stay in the hospital
for six or seven weeks, had rejected offers to treat their heroin habit.

"We would not give a drug of abuse to someone who was seeking treatment,"
she said. "We refer anyone to treatment who would even moderately consider
it."

The medications being tested affect the brain in different ways. Naltrexone
is an antagonist, meaning that it blocks the effect of heroin on the
brain's receptors. Methadone is an agonist, which stifles the craving for
heroin by binding to the brain receptor. The third, buprenorphine, acts as
an agonist at lower doses and as an antagonist at higher doses.

Unlike methadone, naltrexone could be available with just a doctor's
prescription. But because a dose lasts only a day or so and leaves some
users feeling anxious and unhappy, many tend to quit. Fewer than 2,000
heroin addicts nationwide take naltrexone, compared with 115,000 methadone
users.

In one study, the researchers are experimenting with a slow-release form of
naltrexone that lasts 30 days.

The second study, involving buprenorphine and methadone, gives participants
who have received a dose of either drug the chance to perform laboratory
tasks for heroin or for money. If the drug works properly, the addict will
logically choose the cash. But to earn a full dose of heroin or $20, the
participant must work hard, by pushing a button as many as 11,500 times.

The study is taking place while buprenorphine is undergoing approval by the
Food and Drug Administration.

"Buprenorphine may have certain advantages over methadone," Kleber said.
"It's longer acting, easier to withdraw from and has a ceiling effect" on
depressing breathing, he said, making it unlikely that a user could
overdose on it.

The heroin addicts are recruited for the studies through newspaper
advertisements as well as word of mouth. Strict standards for acceptance
exclude anyone who is dependent on other drugs, was convicted of a violent
crime, is on probation or parole or has medical or psychological problems
making them unsuitable participants. And because of the hospital time
involved, the addicts would not be able to hold a job during the test.

The National Institute on Drug Abuse, which is financing all six studies
with $708,000 in grants this year, has issued the program a certificate of
confidentiality so that the names of participants cannot be subpoenaed by
prosecutors or the police. Kleber declined to let addicts in the studies be
interviewed or photographed.

According to the protocol summaries, up to half of them are white, with the
rest primarily black or Hispanic. Roughly a third are women.

"We do everything possible to minimize the risks in terms of the selection
of subjects," Kleber said. They must be physically healthy, from 21 to 45,
and dependent only on heroin, not on other drugs.

The researchers are mindful of reducing the harm that heroin users cause
themselves.

"They take less drugs with us than they would on the street, and they're
being taken better care of," said Kleber, who with Dr. Marc Galanter was
co-editor of ``The American Psychiatric Press Textbook of Substance Abuse
Treatment," which is widely used by health professionals.

First, the volunteers go through several days of detoxification, in which
their heroin is stopped and they are put on sufficient buprenorphine to
suppress the pangs of withdrawal. Then they are given naloxone, a
medication used by emergency room doctors to treat heroin overdoses, to
make them ready for naltrexone. Once this is administered, they go back to
heroin again to see whether it is neutralized by the naltrexone and for how
long.

Because street heroin varies widely in purity, the National Institute on
Drug Abuse supplies the studies with pharmaceutically pure heroin, with the
approval of the Drug Enforcement Administration.