MUSC TESTS POSSIBLE CURE FOR ADDICTIONS

A dietary supplement sold in health food stores may cure cocaine addiction
by curbing cravings and repairing changes that the drug causes in the
brain, doctors at Medical University of South Carolina say.

They are testing the amino acid derivative N-acetylcysteine on people.

In earlier experiments on rats addicted to cocaine, doctors found that an
amino acid restored normal levels of the neurotransmitter glutamate in the
part of the brain long known to be important in addiction. That made lab
rats stop seeking cocaine, a drug that 25 percent of Americans reportedly
have tried.

N-acetylcysteine also may stop cravings for heroin, alcohol and other
addictive drugs, MUSC doctors said Friday. They expect to start testing the
amino acid, a protein building block, next month on rats hooked on heroin.

N-acetylcysteine often is sold as a dietary supplement bearing the letters
NAC and is produced by a number of companies, according to area health food
stores.

"People should not go to the health food store and self-medicate," said
MUSC psychiatrist Dr. Robert Malcolm, who specializes in addiction and is
leading the clinical trial.

Malcolm said the compound is safe as used in the trial. What MUSC patients
receive is certified pure, whereas what's sold in stores is not checked or
controlled by agencies such as the U.S. Food and Drug Administration.

For the earlier study, each white rat was addicted to cocaine by connecting
it to a large syringe filled with the drug and giving it a dose each time
it touched a lever in its cage.

"They get a pretty good rush from the cocaine," said Dr. Peter Kalivas, the
chairman of the MUSC Department of Physiology and Neurosciences.

"In one day, they're pressing away on the lever," said Kalivas, whose study
on rats will be reported in the July issue of Nature Neuroscience. When
Kalivas and his colleagues replaced the drug with saline, a rat would press
the lever about 150 times in hopes of getting cocaine. When given a dose of
the amino acid, a rat still would punch the lever. But after about five
times, the rat stopped pressing.

"In time, it curled up and went to sleep," Kalivas said.

Addictive drugs are known to cause changes in the brain and brain
functioning, he said, but no one had tried to find that brain change.

Kalivas began by looking first at molecular changes and then at rats'
brains to see how cocaine addiction gets implanted in the brain.

Because of a defect in the part of the brain where addiction lies,
glutamate was abnormally low there. N-acetylcysteine restored glutamate
levels to normal.

Rats stopped seeking drugs, which told doctors that the amino acid
suppressed their craving. Results in rats were so impressive that MUSC
quickly cleared the regulatory hurdles and got permission to try
N-acetylcysteine on 12 people. The amino acid also is used to treat cystic
fibrosis and overdoses of acetaminophens such as Tylenol, Malcolm said.

Two patients have taken part in the trial so far and three are being
screened, but Malcolm doesn't expect to complete the study until next year.
(For more information, call 792-5717.)

As in-patients, participants receive the amino acid for three days and are
shown images related to cocaine and unrelated images such as furniture. An
MRI tracks what areas of the brain light up, indicating whether the person
is craving what is being shown. Other tests record physical response to the
images, such as heart rate, sweating and facial muscle movement.

Each patient is tested for three days with the amino acid and three days
with a placebo. Neither patients nor doctors know which is which and won't
until the trial is over.

One patient reported a "miraculous difference," said Dr. Steve LaRowe, who
is conducting the physical testing but is not leaping to any conclusions.

If results look promising, the study will broaden, Malcolm said. The
National Institute of Drug Abuse, which funds Kalivas' work, is anxious to
find treatment, said Malcolm, who expects the amino acid derivative to get
on a fast track for approval.

Other researchers probably will work with alcoholics, Kalivas said, after
information on his rat study is published next month.

Until now, treatments for addiction and psychiatric disorders such as
depression and schizophrenia have involved experimenting to find out what
works, Kalivas said.

But he has seen the changes in molecules and brains that show addiction,
quieted cravings, repair of damage and recovery.

"This is the way we are ultimately going to find cures. I think this will
begin a whole wave of discoveries," Kalivas said.