In animal models, vigabatrin works to reduce the use of virtually every addictive substance
Manhasset, NY (Vocus) November 12, 2009
They were Mexican parolees with an addiction to cocaine. They were also desperate pioneers whose drug use had gotten the better of them every day for years. They signed on to a double-blind, placebo-controlled study to test whether an epilepsy drug could reduce their use of cocaine. In the end, 14 of the 50 parolees who were taking a medicine called vigabatrin spent the final three weeks of the study with no signs of cocaine use on twice weekly urine tests, compared to four of 53 who swallowed a placebo dose. They were also less likely to be drinking alcohol during this same time period.
The study, conducted by Stephen L. Dewey, PhD of The Feinstein Institute for Medical Research in Manhasset, NY, and Jonathan D. Brodie, MD, PhD, of New York University School of Medicine and their colleagues, appears in the November issue of the American Journal of Psychiatry.
Dr. Dewey and Dr. Brodie have spent more than a decade working on animal models, and now drug abusers, following their initial findings that the drug blocks important reinforcement regions of the brain tied to addiction. The scientists just received a $1.2 million grant from the U.S Department of Defense to continue their work in treating human addictions.
"In animal models, vigabatrin works to reduce the use of virtually every addictive substance," said Dr. Dewey. The work was conducted at Brookhaven National Laboratory, where Dr. Dewey had worked from 1996 until moving his laboratory to the Feinstein Institute earlier this year. It was in 1998 when he discovered that the epilepsy drug, which had been approved for use in Europe but not in the United States, showed potential to end cocaine addiction. A year later, it was used for smoking cessation and then methamphetamine. The drug was even used to see if it could reduce cravings for high-sugar, high-fat food.
It was recently approved by the US Food and Drug Administration for use in epilepsy treatment. "If this can do for humans what it did for animals, we may have opened the door for addicts around the world to kick their habit," said Dr. Dewey. Gamma vinyl GABA, or GVG, blocks the chemical process that triggers the "high." The substance increases the amount of the brain's most common neurotransmitter, GABA. The increased GABA allows brain cells to communicate more effectively.
The researchers became interested in GVG because it also reduces the level of another brain chemical called dopamine. This brain substance has been shown to modulate pleasure and reward, as well as other behaviors. Cocaine users experience a "high" because the drug - and other mind-altering substances - seems to stimulate a flood of dopamine in the brain regions that govern reinforcing and rewarding behavior in humans and animals alike. Dopamine is known as the "feel-good" transmitter, although it has many different roles in the brain. Vigabatrin reduces levels of dopamine in the circuits of the brain that govern reward.
About 30 million people in the United States have used cocaine, and about one to three million would be considered addicted, experts say. There are no medicines approved for cocaine addiction.
The current study is the first double-blind, placebo-controlled study of the drug in addicts. The men and women who signed on to the trial arrived to the clinic as part of their parole requirements after being released from prison. They had an average daily use of two grams per day for about nine years. They agreed to be part of the study even though half of them would end up on a placebo. The medicine is a powder that they mixed with orange juice.
At the end of three months, four times as many people taking vigabatrin completely stopped using cocaine for at least three weeks compared to those swallowing a placebo powder in their juice. They were also far more likely to report abstinence from alcohol.
There have been concerns moving forward with this drug. One of the reasons it was not approved in the U.S. until recently was that there is a rare but troubling side effect: a narrowing of visual field. And there are indications these defects could grow more serious over time.
Dr. Dewey and Dr. Brody teamed with a biotech company - Catalyst Pharmaceutical Partners - that has licensed the use of the drug for the treatment of cocaine addiction. They have a long way to go before vigabatrin could be used to treat addictions. They need much larger studies and must figure out how much to give and whether it could be given over a long-term period. In the current study, the only side effect was tiredness.
Dr. Dewey's research on the addicted brain has led him into Long Island schools to educate young people, parents and teachers on the dangers of the brain on drugs. His lectures and town hall meetings have become so popular that he was asked last month to speak to The Welfare to Work Commission of the Suffolk County Legislature during a public meeting on a growing network of "sober homes."
About The Feinstein Institute for Medical Research
Headquartered in Manhasset, NY, The Feinstein Institute for Medical Research is home to international scientific leaders in cancer, leukemia, lymphoma, Parkinson's disease, Alzheimer's disease, psychiatric disorders, rheumatoid arthritis, lupus, sepsis, inflammatory bowel disease, diabetes, human genetics, neuroimmunology, and medicinal chemistry. Feinstein researchers are developing new drugs and drug targets, and producing results where science meets the patient, annually enrolling some 10,000 subjects into clinical research programs.
Contact: Jamie Talan, science writer-in-residence
516-562-1232 or 631-682-8781 (cell)