Pubdate: Tue, 22 Feb 2005 Source: Macon Telegraph (GA) Copyright: 2005 Philadelphia Newspapers Inc Contact: http://www.macontelegraph.com/ Details: http://www.mapinc.org/media/667 Author: Stacey Burling /Philadelphia Inquirer Bookmark: http://www.mapinc.org/rehab.htm (Treatment) FIGHTING DRUGS WITH DRUGS IS LATEST ADDICTION THERAPY PHILADELPHIA - The weapon of the future in the war on drugs will likely be .. drugs. Researchers are optimistic about a host of new medications that target the chemical cycle of addiction. Some block the intense pleasure that makes drugs such as heroin so seductive while others calm the brain during withdrawal. Long-acting versions of two drugs already approved - naltrexone for heroin addicts and alcoholics, and buprenorphine for opiate addicts - are on the horizon. They should combat one of the biggest treatment problems: Addicts often dislike taking anything that prevents getting high. Other researchers are taking a different tack, testing vaccines that teach the body to treat illicit drugs like invading microbes. Addiction experts say that advances in brain science, especially brain imaging, have led to the testing of more promising medications than ever before. Plus, this exploding scientific knowledge is revealing ever more targets for future medicines. "I think there are a lot of opportunities to develop new drugs," said Raye Litten, coleader of the medications development team at the National Institute on Alcohol Abuse and Alcoholism. It remains to be seen how many medicines under scrutiny - several are already approved for other uses - will work against addiction long term. None is a cure. If they work, though, experts say the country is ill-prepared to use them. Many treatment programs have a drug-free agenda that predates effective medications. Most do not have doctors. Experts say no medicine is a substitute for the therapy and self-help groups that constitute most treatment now. Nationally, 12.4 million people are addicted to alcohol, cocaine, stimulants such as methamphetamine, marijuana, heroin and other opioids. About 35.7 million are addicted to nicotine. In the last three years, two new medications joined the small band of addiction drugs. The Food and Drug Administration approved buprenorphine, a relatively mild narcotic, for opioid addiction in 2002. The drug can be prescribed by community doctors, but they can treat only 30 patients at a time, and many have waiting lists. Last month, pharmacies received their first shipments of acamprosate (Campral), the first new drug for alcoholism since naltrexone. When alcoholics quit drinking, their brains can malfunction chemically for as long as a year, said researcher Barbara Mason of the Scripps Research Institute in California, who helped test the drug. Campral, she said, helps restore balance. In recent years, scientists have come to see addiction as a cycle of reward and craving that transcends particular substances. As a result, researchers are realizing that medications may work for more than one kind of addiction. Addictive substances tend to affect the same parts of the brain and disrupt the same neurotransmitters: dopamine, GABA and glutamate, said psychiatrist Charles Dackis of the University of Pennsylvania's Treatment Research Center. Dopamine, a neurotransmitter involved in feeling pleasure, is a key player. It's nature's way of rewarding animals for behavior that increases odds of survival, activities such as sex, hunting and eating. Addictive drugs tap into the dopamine system and flood the brain with this substance in a way that no natural activity can. That pleasure can be irresistible. "All lab animals will self-administer cocaine to death," Dackis said. GABA and glutamate help to regulate dopamine. GABA inhibits it. Glutamate drives it. Both are involved in craving, the main reason that addicts backslide so frequently. Just the sight of something addicts link to drugs - money, a drinking buddy, a hypodermic needle - can trigger powerful brain changes, Dackis said. Imaging shows the response is the same as nonaddicts have when they see sexually explicit movies. Over time, Dackis said, addiction causes brain changes that make quitting harder. The dopamine system gets off-kilter, and normally pleasurable activities don't feel as good. Also, many drugs, especially stimulants, impair the prefrontal cortex. The seat of rational thinking, it regulates the nucleus accumbens, which Dackis called "the universal addiction site." All these aspects of addiction suggest possible targets for anti-addiction drugs. Researchers also are paying more attention to genes. Not everyone who tries an addictive drug becomes dependent, partly because of heredity. Even addicts can be quite different. In the future, experts said, doctors may target specific drugs to specific addicts. For example, preliminary research suggests that Antabuse, a medicine that makes drinkers sick, may help nondrinking cocaine addicts. Naltrexone may work best in another subset of hereditary alcoholics who feel high when they drink rather than sedated, said Charles O'Brien, a Penn addictions expert. John Bauhs, a 41-year-old Washington alcoholic with alcoholism on both sides of his family, joined a Penn study aimed at sorting out who responds to naltrexone. Bauhs has been sober for seven months since starting naltrexone. His previous record: six weeks. The drug is "amazing," he said. "What it does is take away the urge and the benefit of alcohol." Even with the new medications, many patients go back to using. Boasting abstinence rates two to three times the unmedicated norm, Campral was good enough to get FDA approval. But at three months, just 38 percent of patients on the drug had managed not to drink at all. Modafinil, one of several drugs being studied for cocaine addiction, helped a third of patients stay off cocaine for three weeks, compared with 13 percent of patients on placebo. Experts are optimistic that better medicines will come. Meanwhile, they said, the fact that the medicines don't cure addiction is no reason to reject them. "Does insulin cure diabetes?" asked Herbert Kleber, a Columbia University psychiatrist and addictions expert. "Does any drug cure schizophrenia?" Addiction experts say the country's primary-care doctors and drug treatment centers will have to change to make best use of the new medicines. Few treatment programs employ doctors, and few community doctors know enough about addiction medicines to feel comfortable prescribing them, the experts said. "They're divorced worlds," said Tom McLellan, director of Penn's Treatment Research Institute. The country needs more addiction medicine specialists because of the new drugs and the growing recognition that many addicts need psychiatric medications, said H. Westley Clark, director of the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment. Bauhs is an example of how rarely doctors think of using drugs for addiction. He has tried more than a dozen treatment regimens. No one ever told him about naltrexone, a drug approved for alcoholism in 1995. He discovered Penn's naltrexone study on the Internet. "What amazes me is that it's not more readily known or available," he said. - --- MAP posted-by: Jay Bergstrom