DRUG'S EFFECT ON BRAIN IS EXTENSIVE, STUDY FINDS

Heavy users of methamphetamine - a highly addictive stimulant that can be
made at home in the kitchen sink - are doing more damage to their brains
than scientists had thought, according to the first study that looked
inside addicts' brains nearly a year after they stopped using the drug.

At least a quarter of a class of molecules that help people feel pleasure
and reward were knocked out by methamphetamine, the study found. Some of
the addicts' brains resembled those of people with early and mild
Parkinson's disease. But the biggest surprise is that another brain region
responsible for spatial perception and sensation, which has never before
been linked to methamphetamine abuse, was hyperactive and showed signs of
scarring.

On tests of memory, attention and movement, the methamphetamine addicts did
worse compared with people who do not use drugs, the study reported. The
researchers said it was too soon to know if people who stopped taking the
drug for more than a year would recover lost brain function.

The study was led by Dr. Nora Volkow, associate director for life sciences
at the Brookhaven Haven National Laboratory in Upton, N.Y., and appears in
the March issue of The American Journal of Psychiatry.

This is the first study to show directly that brain damage caused by
methamphetamine produces deficits in learning and memory, said Dr. Alan
Leshner, director of the National Institute on Drug Abuse, which helped
finance the new research. Use of the drug has reached epidemic proportions
in Hawaii, California and parts of the Midwest, he said. Made in
clandestine laboratories from cheap ingredients, it is known as speed,
meth, chalk, ice, crystal and glass. The drug can be smoked, snorted,
injected or taken by mouth. A $5 dose produces euphoria and increases
energy for hours, whereas a cocaine high may last only half an hour.

It's not clear why some people choose cocaine over methamphetamine or vice
versa, Dr. Volkow said. Estimates are that five million American have
experienced methamphetamine and maybe one million to two million are
regular users. "It's a bigger problem that heroin," she said.

Over the years, the addicts in the study had taken pounds of
methamphetamine, an amount that is enough to kill laboratory animals, Dr.
Volkow said. "Actually, I am stunned these people are not dead."

In the study, Dr. Volkow used an imaging technique called positron emission
tomography to measure dopamine levels in the brains of 15 recovering
addicts and 18 healthy volunteers. Dopamine is a brain chemical that
regulates movement, attention, pleasure and motivation. When the dopamine
system goes seriously awry, she said, people lose their excitement for life
and can no longer move their limbs. Their brains were then imaged a second
time to measure how different parts of their brains metabolize energy.

The addicts smoked or injected methamphetamine all day for several years,
Dr. Volkow said. They had started out as occasional users but over time the
drug hijacked their natural dopamine systems. Two weeks after the brain
images were taken, the addicts and the volunteers were brought back to the
laboratory and asked to do tasks like walking as fast as possible in a
straight line, rapidly inserting pegs into small holes angled in different
directions, matching numbers with symbols, recalling lists of unrelated
words and carrying out other tests that measure brain acuity.

On average, dopamine was 24 percent lower in addicts than in normal
volunteers, Dr. Volkow said. They were clumsier at putting pegs in the
holes and had difficulty remembering words. Half the addicts said they felt
their brains were not working as well as they used to.

But the study's biggest surprise was that the addicts' parietal lobes, the
parts of the brain used for feeling sensation and recognizing where the
body is in space, were metabolically overactive, Dr. Volkow said. Other
studies showed that metabolism increased when the brain suffered traumatic
injury or got high doses of radiation, she said. It is the equivalent of an
inflammation or scarring response.

The loss of dopamine is also worrisome, Dr. Volkow said. Three drug abusers
had dopamine levels that fell within the range seen in patients with
low-severity Parkinson's disease. Because dopamine levels fall naturally
with age, it's unclear what will happen to these people 30 years from now.

"We don't know if they will recover dopamine function or not," she said.

Five of the fifteen addicts have not relapsed and are being re-examined
with brain imaging to see if their dopamine levels rebound. All smoke
heavily, and it may be that nicotine protects their brains from being more
severely damaged, she said. If that is the case, treatments for
methamphetamine abuse might include nicotine patches and drugs to enhance
dopamine function along with behavioral therapy.