Pubdate: Sat, 21 Jun 2003 Source: Post and Courier, The (Charleston, SC) Copyright: 2003 Evening Post Publishing Co. Contact: http://www.charleston.net/ Details: http://www.mapinc.org/media/567 Author: LYNNE LANGLEY MUSC TESTS POSSIBLE CURE FOR ADDICTIONS A dietary supplement sold in health food stores may cure cocaine addiction by curbing cravings and repairing changes that the drug causes in the brain, doctors at Medical University of South Carolina say. They are testing the amino acid derivative N-acetylcysteine on people. In earlier experiments on rats addicted to cocaine, doctors found that an amino acid restored normal levels of the neurotransmitter glutamate in the part of the brain long known to be important in addiction. That made lab rats stop seeking cocaine, a drug that 25 percent of Americans reportedly have tried. N-acetylcysteine also may stop cravings for heroin, alcohol and other addictive drugs, MUSC doctors said Friday. They expect to start testing the amino acid, a protein building block, next month on rats hooked on heroin. N-acetylcysteine often is sold as a dietary supplement bearing the letters NAC and is produced by a number of companies, according to area health food stores. "People should not go to the health food store and self-medicate," said MUSC psychiatrist Dr. Robert Malcolm, who specializes in addiction and is leading the clinical trial. Malcolm said the compound is safe as used in the trial. What MUSC patients receive is certified pure, whereas what's sold in stores is not checked or controlled by agencies such as the U.S. Food and Drug Administration. For the earlier study, each white rat was addicted to cocaine by connecting it to a large syringe filled with the drug and giving it a dose each time it touched a lever in its cage. "They get a pretty good rush from the cocaine," said Dr. Peter Kalivas, the chairman of the MUSC Department of Physiology and Neurosciences. "In one day, they're pressing away on the lever," said Kalivas, whose study on rats will be reported in the July issue of Nature Neuroscience. When Kalivas and his colleagues replaced the drug with saline, a rat would press the lever about 150 times in hopes of getting cocaine. When given a dose of the amino acid, a rat still would punch the lever. But after about five times, the rat stopped pressing. "In time, it curled up and went to sleep," Kalivas said. Addictive drugs are known to cause changes in the brain and brain functioning, he said, but no one had tried to find that brain change. Kalivas began by looking first at molecular changes and then at rats' brains to see how cocaine addiction gets implanted in the brain. Because of a defect in the part of the brain where addiction lies, glutamate was abnormally low there. N-acetylcysteine restored glutamate levels to normal. Rats stopped seeking drugs, which told doctors that the amino acid suppressed their craving. Results in rats were so impressive that MUSC quickly cleared the regulatory hurdles and got permission to try N-acetylcysteine on 12 people. The amino acid also is used to treat cystic fibrosis and overdoses of acetaminophens such as Tylenol, Malcolm said. Two patients have taken part in the trial so far and three are being screened, but Malcolm doesn't expect to complete the study until next year. (For more information, call 792-5717.) As in-patients, participants receive the amino acid for three days and are shown images related to cocaine and unrelated images such as furniture. An MRI tracks what areas of the brain light up, indicating whether the person is craving what is being shown. Other tests record physical response to the images, such as heart rate, sweating and facial muscle movement. Each patient is tested for three days with the amino acid and three days with a placebo. Neither patients nor doctors know which is which and won't until the trial is over. One patient reported a "miraculous difference," said Dr. Steve LaRowe, who is conducting the physical testing but is not leaping to any conclusions. If results look promising, the study will broaden, Malcolm said. The National Institute of Drug Abuse, which funds Kalivas' work, is anxious to find treatment, said Malcolm, who expects the amino acid derivative to get on a fast track for approval. Other researchers probably will work with alcoholics, Kalivas said, after information on his rat study is published next month. Until now, treatments for addiction and psychiatric disorders such as depression and schizophrenia have involved experimenting to find out what works, Kalivas said. But he has seen the changes in molecules and brains that show addiction, quieted cravings, repair of damage and recovery. "This is the way we are ultimately going to find cures. I think this will begin a whole wave of discoveries," Kalivas said. - --- MAP posted-by: Keith Brilhart