In the last few years the study of drug addiction has been revolutionized by the discovery that the brain chemicals dopamine and glutamate are largely responsible for a drug’s pleasurable rush. With this knowledge scientists have begun to unravel how drug activity in the brain causes addiction. And knowing this is the first step to devising new treatments. Some of the drugs that affect dopamine and glutamate are alcohol, nicotine, cocaine and amphetamines. Scientists have begun looking for drugs that will counteract the effects drugs have on these neurotransmitters.
Dopamine and glutamate provide a one-two punch that pleasures the brain and produces long-term changes in its structure. Dopamine stimulates brain cells called neurons in many different areas of the brain, but scientists have determined that the region called the nucleus accumbens is responsible for perceptions of pleasure, whether or not drugs are involved. Glutamate follows dopamine, provoking similar feelings of pleasure, and may also be responsible for altering the brain’s structure to produce the long-term cravings that can lead to addiction.
Some of the drugs that affect dopamine and glutamate are alcohol, nicotine, cocaine and amphetamines. Scientists have begun looking for drugs that will counteract the effects drugs have on these neurotransmitters.
One drug, gamma vinyl-GABA, or GVG, has shown great promise in treating addiction by blocking the surge of dopamine activity caused by drugs such as nicotine and cocaine. GVG has been used in the past in other countries to treat epilepsy. GVG works by permanently binding to an enzyme that breaks down GABA, aneurotransmitter that damps brain activity. GVG stops the enzyme from deactivating GABA, causing GABA levels to rise and rein in dopamine’s stimulatory effects. Scientists Stephen Dewey and Jonathan Brodie found that in rats dopamine levels rise by up to 500% after ingesting cocaine. GVG cuts this rise to 250%. A similar effect was also seen in baboons, whose brains are more similar to human brains than rat brains are. GVG also blocks the dopamine rise in rats addicted to nicotine.
Scientists will still have to run tests on human subjects to measure the safety and efficacy of GVG. One known side effect of treating people with GVG for epilepsy is a reduction in peripheral vision. If scientists can use a lower dose for treating drug addicts they may be able to escape this problem, which is GVG’s only serious side effect.
At present there are very few drugs available to treat drug addiction. The few that do exist, such as Antabuse for alcoholism and methadone for heroin addiction, have unpleasant, and even fatal, side effects. For treating nicotine addiction, patches or chewing gums deliver nicotine more safely, and antidepressant drugs such as Zyban are used to treat the depression that often accompanies quitting smoking.
Drug companies haven’t made developing treatments a priority. Addicts forget or quit their medications so frequently that it is difficult for the companies to make money from regular sales, even though there are plenty of treatment candidates. As well, some doctors remain opposed to treating drug addictions with more drugs. They view it as switching one addiction for another and prefer to use traditional 12-step programs and psychotherapy to treat addicts. But as drugs like GVG are developed, some doctors are becoming more interested in treating drug addicts with such drugs.
One of the biggest problems in helping addicts quit is controlling the urges and cravings that come in the first few months after quitting a drug. Addicts often make psychological associations with the places and things associated with taking drugs, and seeing or touching them again can bring on strong cravings. For instance, crack addicts seeing a crack pipe will experience strong cravings as will nicotine addicts having an alcoholic drink or coffee, since these objects and activities were formerly associated with taking the drug. Even being in a room where they routinely took drugs can bring back memories and stoke cravings.
Scientists believe they may be able to control these cravings by limiting glutamate’s actions on the brain. At the end of the 1980s Ralph Karler first discovered that blocking glutamate transmission in rat brains prevents behavioral sensitization. This occurs when repeated, equivalent doses of a drug cause an animal to behave more and more frantically. Researchers now believe glutamate is responsible for stimulating these effects and subsequent cravings. Neurons that transmit glutamate are found throughout the brain’s cerebral cortex, the seat of many thought processes. Many of these neurons also extend their reach into the nucleus accumbens, the same pleasure region stimulated by dopamine.
One team of researchers studied the brain activity of addicts who were shown pictures of drug paraphernalia. Using positron emission tomography to measure blood flow to the different regions of the brain, the scientists found that the intensity of the addicts’ cravings paralleled activity in two different brain regions, the amygdalaand the frontal cortex. Both of these areas contain neurons that release glutamate on the nucleus accumbens. These regions are also associated with learning and memory, adding further support to the view that memories and increased glutamate transmission may fuel cravings.
One drug that may be able to block these cravings is acamprosate. In the past few years acamprosate has been tested in Europe for the treatment of alcoholism. The largest trial involved 4,000 people across Europe. After one year of treatment, 39 percent of the people treated with acamprosate remained abstinent, compared to 17 percent in the untreated group. Many of the subjects said they had few or no problems with cravings while taking acamprosate.
Scientists still don’t know how acamprosate works. Many suspected that it dampens glutamate neurons, stopping the enhanced firing. But one team of researchers showed that acamprosate actually turns on glutamate signaling, suggesting that cravings during withdrawal may be stimulated by abnormally low glutamate activity. Acamprosate may increase the brain’s glutamate signals. Either way, physicians may soon have a new weapon for treating alcoholism.
Sources:
“Scientists Identify Brain Chemicals Involved in ‘Switching On’ Cocaine Addiction.” (www.nida.nih.gov/ MedAdv/ 99/ NR-915.htm) Site posted by the National Institute on Drug Abuse (NIDA;, features a press release about the cocaine addiction research.
“Cocaine Vaccine Blunts Craving In Addicted.” (www.mapinc.org/ drugnews/ v99.n908.a06.html/coke) Site features a news article about research into a cocaine vaccine.
“New Drug Shown To Treat Wide Range of Addictions.” (unisci.com/stories/ 19993/ 0823994.htm) Site features an article about gamma vinyl-GABA as well as a link to related stories.
