Can Drugs Cure Drug Addiction?

By ANDREW PURVIS

When methadone was first introduced 24 years ago, it was hailed as a magic bullet aimed at the heart of heroin addiction. A neat, clean medical solution to a social problem. It has proved to be something less than that. Methadone is a treatment, not a cure, for addiction, and an imperfect one at that. But for some 100,000 of the country's half-million heroin addicts, it offers an alternative to shooting up as well as the possibility of a productive life.

With the crack epidemic spiraling out of control and the continuing threat of AIDS transmission through needle sharing, the research community and government leaders are showing new interest in medical approaches to drug addiction. After nearly a decade of relative neglect under the "Just Say No" Reagan Administration, the Federal Government has sharply increased funding to the National Institute on Drug Abuse, which sponsors almost all of the world's drug-abuse research. In the past year NIDA's medications and basic-research budget jumped 50%, to $75 million, and Congress promises similar increases in the future. "It's the Manhattan Project for chemists in the war on drugs," declares Duncan Taylor, a senior researcher at Bristol-Myers.

The most promising of several drugs to combat addiction that are being tested is buprenorphine, a pain reliever that in early trials has shown clear advantages over methadone as a treatment for heroin addiction. Under development by a team at Yale University, the drug, like methadone, induces a generalized feeling of contentment rather than heroin's precipitate rush and euphoria. It is at least as effective as methadone in easing physical withdrawal and reducing cravings, and it is significantly more potent in blocking heroin's high if the addict tries to shoot up again. Unlike methadone, buprenorphine is relatively nonaddictive and carries almost no risk of overdose. In one trial of 41 addicts on methadone maintenance, it cut the number of those who continued to take heroin to just over half and eased 18 off opiates altogether.

- As a bonus, buprenorphine seems radically to suppress the urge to take cocaine, which is abused by an estimated 70% to 80% of heroin addicts. Methadone also tends to reduce coke use, but less dramatically. While methadone may wean half of those treated from cocaine, buprenorphine could slash the number of coke abusers to almost nil, says Yale researcher Thomas Kosten. A Harvard study of rhesus monkeys habituated to using coke found that daily doses of buprenorphine led the monkeys to kick the habit completely.

Other medications being used for psychiatric or neurological conditions are also showing some promise. Flupenthixol, currently prescribed overseas for schizophrenia, seems to soften the "crash," a unique combination of depression and craving that follows one cocaine binge and typically leads to another round. In preliminary trials on a group of ten Bahamian crack addicts seeking treatment, researchers from Yale found that even low doses kept users off cocaine for the two-month duration of the trial. Another drug, carbamazepine, long taken to prevent seizures, has proved to be moderately effective against cocaine craving. In tests this year, six of 13 people taking the drug stopped using cocaine and the remaining seven reduced their intake about two-thirds. Researchers got the idea for using this antiseizure drug after hearing reports that low doses of cocaine triggered mini-seizures in some animal brains and that this "kindling" in the brain might be linked to craving. By next year, NIDA expects to have eight to twelve antiaddiction medications in clinical trials.

Still, scientists are not expecting miracles, particularly in battling cocaine addiction. Unlike heroin, which acts on the pain-killing endorphin system alone, cocaine engages three separate neurotransmitter systems: those based on dopamine, serotonin and norepinephrine. Taken together, these networks govern the human ability to experience pleasure, from watching a sunrise to having sex. Blocking all these pleasure centers -- as methadone blocks the heroin high -- would literally take the joy out of life, says Yale's Kosten. "We'd turn out automatons." Addicts trying to quit cocaine go through a stage called anhedonia, a sort of spiritless limbo that typically drives the user to take the drug again. At best, researchers can hope for a patchwork of drugs to block discrete stages of cocaine withdrawal, such as craving and depression.

It is far from clear that the new drugs will succeed even in this limited way. None have been tested in a full-scale trial designed to mimic the conditions addicts encounter on the street. Buprenorphine, which is one of the furthest along in testing, is unlikely to receive approval before 1992. Scientists also readily concede that medical therapy fails to address the underlying psychological and social causes of drug abuse. Even if an addict is weaned from one drug, they say, he will very often take up another. A federal study released in August found that as many as 47% of patients at 15 methadone clinics across the country continued to use heroin or other opiates, and up to 40% used nonopiate drugs, usually cocaine. So scientists find themselves aiming their magic bullet at a moving target. "We're constantly having to treat new disease," said Marvin Snyder, director of NIDA's medications- development program. "In five years, the problem may not be cocaine, but some drug we haven't even heard of."