| DECEMBER 2, 1998
Epilepsy Drug Stops Nicotine's Effects in Animals
Same Drug Already Shows Promise in Animals
For Treating Cocaine Addiction
Washington, DC - Smokers who want to kick the habit may find
powerful help from a European epilepsy drug that already has shown
promise in treating cocaine's effects in animals, U.S. Secretary
of Energy Bill Richardson announced today.
That is the conclusion of animal studies published today in the
journal Synapse by scientists from the U.S. Department
of Energy's Brookhaven National Laboratory (BNL), St. John's University,
New York University School of Medicine and the Albert Einstein
College of Medicine.
"Smoking-related diseases are responsible for 1 in 5 deaths
in the U.S.," said Energy Secretary Bill Richardson at a
press conference. "With 35 million smokers trying to quit
each year, and only 7 percent succeeding for more than a year,
this new effort, if successful, could save millions of lives.
Once again, government-funded scientists are at the forefront
of the cutting- edge research enabling us to confront a major
The same team published results in August showing that the
epilepsy drug -- known as gamma vinyl-GABA, or GVG -- looks very
promising as a treatment for cocaine addiction. In animals, it
prevented the dramatic changes in brain chemistry and behavior
brought on by cocaine.
The new paper shows that GVG does the same for nicotine. And,
the dose needed to block nicotine was about one-tenth of that
used to block cocaine's effects in animals. The nicotine-blocking
dose corresponds to about one-tenth to one-twentieth the dose
currently used to treat epilepsy in humans. Upcoming clinical
trials will determine the dosage needed in humans.
According to Dr. Alan I. Leshner, director of the National
Institute on Drug Abuse, National Institutes of Health, "This
study confirms the importance of the brain's GABA system as an
important target for potential anti-addiction medications, like
GVG. It also emphasizes that there likely are common brain mechanisms
underlying addiction to all drugs and gives hope that we can develop
a single medicine to use in treating addiction, whatever the primary
The evidence is so strong that the scientists think GVG might
work better and have fewer side effects than other stop-smoking
treatments available today. It is not addictive, is not based
on nicotine and has been used safely in Europe by epileptic children
for more than a decade.
"Of all the addictive drugs that exist, nicotine is the
most frequently abused drug in the world, and every smoker who's
tried knows how hard it is to quit," said Stephen Dewey,
the lead author on the paper. "We've shown in animals that
the proper dose of GVG can stop nicotine's addictive effects entirely."
The team's research also suggests that GVG may work against
a variety of other addictions.
"We're gaining confidence that this approach could offer
hope to all addicts, from smokers and alcoholics to hard-core
heroin and cocaine users," said team member Charles Ashby
of St. John's.
Added co-author Jonathan Brodie of New York University, "Since
the same brain chemistry changes may be common to all these addictions,
it follows that a single well-aimed strategy, combined with a
person's desire to quit, could assist in defeating them all."
In order to show whether GVG could be as effective in humans
as it was in animals, clinical trials are now being planned at
institutions in Europe, Canada and the United States.
Though GVG is not currently approved in the U.S. to treat epilepsy,
U.S. institutions can apply to conduct clinical trials under "investigative
new drug" protocols from the federal Food & Drug Administration.
The research grew out of pioneering cooperative work to understand
the brain's chemical messengers, called neurotransmitters, and
the effect of addictive drugs on the balance of those chemicals
in the brain. One neurotransmitter in particular, called dopamine,
plays a central role in the sensations and behaviors associated
with all drug use.
The GVG results on cocaine were published after more than a
decade of investigation that started when Dewey and Jonathan Brodie
of New York University looked at the way brain cells talk to one
another, especially in people with schizophrenia. Soon after
receiving encouraging results on cocaine, the team began testing
GVG against other addictive substances. Work on alcohol, heroin,
morphine, amphetamines and methamphetamines is nearing completion.
Fighting Tobacco's Addictive Hook
The researchers looked carefully at how different doses of
GVG changed nicotine's ability to alter brain dopamine levels
in rodents and primates. They used sophisticated imaging techniques
to measure dopamine concentrations in the brains of both nicotine-addicted
rodents and those that had never been exposed to nicotine. And
they performed brain scans on female baboons given intravenous
"Nicotine doubles the brain's dopamine level, sending
a rush of pleasure and a signal that you should smoke over and
over again," said Dewey. "But an appropriate dose of
GVG taken before nicotine exposure can completely block nicotine's
effects on brain dopamine."
GVG increases the levels of another brain chemical, GABA, which
decreases dopamine production. So, GVG prevents nicotine from
causing dramatic changes.
Studying the Behavioral Effects
As any smoker will attest, nicotine addiction is not just a
matter of the mild rush caused by smoking. The mere sight or
smell of cigarettes, or of a smokers' hangout, can bring on a
This kind of behavioral effect is what makes quitting smoking
so hard. So, Ashby and his colleagues tested GVG's effect on
rats' tendency to seek out a place where they had previously received
nicotine, and their ability to acquire that tendency in the first
place. The technique is called conditioned-place preference,
"It was astounding," said Ashby. "Not only
could GVG keep addicted animals from returning to the nicotine-associated
place -- a somewhat higher dose kept non-addicted ones from getting
the habit in the first place." He noted that similar tests
have not been done on stop-smoking therapies currently on the
The research was funded by the Energy Department, the National
Institute on Drug Abuse and the National Institute of Mental Health.
In addition to Dewey, Ashby and Brodie, the paper's authors are
Bryan Horan of St. John's, Madina Gerasimov of BNL and Eliot Gardner
GVG studies at Brookhaven
The Department of Energy's national laboratory system houses
world-class facilities where more than 30,000 scientists and engineers
perform cutting-edge research spanning DOE's science, energy,
national security and environmental quality missions. The medical
imaging technique used to help establish GVG's effects was developed
largely at Brookhaven as an application of particle accelerator
technology used for high energy physics research. The technique
was applied in support of the department's historical mission
to develop nuclear medicine technologies.
The U.S. Department of Energy's Brookhaven National Laboratory
creates and operates major facilities available to university,
industrial and government personnel for basic and applied research
in the physical, biomedical and environmental sciences, and in
selected energy technologies. The laboratory is operated by Brookhaven
Science Associates, a not-for-profit research management company,
under contract with the U.S. Department of Energy.
- DOE -