Controlling the Habit
An epilepsy drug that is widely used in Canada and Europe may be able to block the craving for cocaine, nicotine and other addictive drugs, researchers from the Brookhaven National Laboratory said Wednesday.
The Brookhaven team has demonstrated in rodents and primates that the drug, called GVG, can block both the ability of cocaine to produce a “high” and the behavioral conditioning that often triggers desire for the illegal drug.
They have not yet tested GVG on nicotine and other drugs of abuse, but they believe that it should have a similar effect because those drugs employ the same biological mechanism to produce pleasurable responses.
And because the drug has already been shown to be safe and non-addicting in humans, the researchers say, they will be able to begin testing its efficacy soon, perhaps within the next couple of months.
“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 and for society to stop the costly cycle of addiction, violence and wasted lives,” said neuroanatomist Stephen Dewey of the Long Island, N.Y. laboratory. “We are unaware of any other drug that has looked as promising.”
Although critics scoff at the idea of using a drug to treat drug dependence, that approach has achieved measurable success. Methadone is quite valuable for treating heroin users, naltrexone for controlling alcohol abuse and nicotine patches for combating smoking. But there is no comparable drug for cocaine users, who number as many as 2 million in the United States.
An anti-cocaine medication is “the greatest single need that we have in this country for dealing with drug abuse and addiction,” said Dr. Alan Lesher, director of the National Institute on Drug Abuse. “These exciting preclinical data point to a major new approach.”
The institute will place as many as 35 new anti-cocaine medications into clinical trials this year in the search for an effective agent. Many of those drugs will be undergoing their first safety trials, however, and others are thought to have a strong potential for addiction themselves.
GVG stands for gamma-vinyl-GABA, which is also known as vigabatrin, or by the trade name Sabril. It has been used for nearly 15 years in Europe and for a shorter time in Canada to prevent certain types of epileptic seizures.
It is in the final stages of clinical trials in the United States, and its manufacturer, Hoechst Marion Roussel, expects to receive marketing approval from the Food and Drug Administration in October.
GVG increases levels of the brain’s most common neurotransmitter, gamma-aminobutyric acid, thereby enabling better communication between brain cells.
But researchers also have found that GVG lowers the level of another transmitter, called dopamine, in the region of the brain that is involved in addiction. High concentrations of dopamine are believed to produce the pleasurable effects associated with cocaine, nicotine and other drugs of abuse.
A similar process occurs in most other animals as well, making them good models for studying new medications. Mice, for example, can learn to depress a lever that gives them a small dose of cocaine. They will continue pressing it to the exclusion of all other activities, even to the point of death. When cocaine is not available, they will hang around in the area of the lever, waiting for more.
Dewey and his colleagues from several institutions in the metropolitan New York area have been studying GVG for 12 years. When they treated addicted mice with it, the mice rarely pushed the cocaine lever and no longer hung around in its area, Dewey said.
That is an important finding, said psychologist Charles Ashby of St. John’s University, because a cocaine craving can be triggered by the addict’s exposure to surroundings that he associates with previous use of the drug. The mouse results indicate that GVG can block that behavioral component of addiction, he said.
The researchers also used a sophisticated imaging technology--
called positron emission tomography or PET scanning--to determine the level of dopamine in the brains of adult baboons given either cocaine or cocaine and GVG. The animals given cocaine alone had very high levels of dopamine, while those given GVG before cocaine had normal levels, the team reports in the August issue of the journal Synapse.
The group plans to begin human trials as soon as the FDA approves the marketing of GVG for epilepsy--meaning that it can legally be prescribed for other uses. They also will begin testing its use for breaking smoking addiction.
Several other approaches to cocaine addiction also are being tested.
ImmuLogic Pharmaceutical Corp. of Waltham, Mass., has developed a vaccine that would trigger the production of antibodies against cocaine. The antibodies tie the drug up before it can reach the brain. Trials of the vaccine began in April.
Researchers at the Scripps Institute and Columbia University have developed man-made antibodies that would bind to cocaine and break it down into molecules that do not produce highs. Neither antibody approach, however, would affect craving.
Guilford Pharmaceuticals Inc. of Baltimore has developed an experimental drug, Compound 2138, that blocks the action of a molecule that transports dopamine through the brain. Tests in animals have shown that the drug blocks the ability of dopamine to produce a high without interfering with its normal beneficial effects.
Other drugs that are being tested include selegiline, a Parkinson’s disease medication, and amantadine, which is used to combat influenza. Those two drugs, as well as many other experimental compounds, alter dopamine levels in the brain.
Researchers also are looking at drugs, such as propanolol and corticotropin-releasing factor antagonists, that would ease the stress and anxiety associated with withdrawal from cocaine.
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Blocking Addiction
CVG, an epilepsy drug that shows potential for use in treating cocaine addiction,blocks the production of dopamine in the brain. PET scans of baboon brains before drug use show normal levels of dopamine, while scans after cocaine use show much higher levels of neurotransmitter. Administering CVG to the animals before cocaine use blocks the drug’s effect, keeping dopamine at normal levels.
Source: Brookhaven National Laboratory
