Drug Seems to Block Users’ Cocaine Need
A pain-killing drug dramatically reduces the craving for both cocaine and heroin and may become an extremely potent tool in the fight against drug abuse, Harvard scientists report today in a paper published in the journal Science.
Although researchers now use antidepressants to help wean cocaine addicts from their addiction, there is now no medication that effectively blocks the craving for cocaine, which is regularly used by as many as 3 million Americans.
The Harvard researchers report that buprenorphine, a drug that is already being studied for use in treating heroin addiction, almost completely halts self-administration of cocaine by rhesus monkeys, which are widely used as a model for human drug addiction.
Anecdotal evidence of scattered human use has suggested that the drug may be equally effective in people and researchers are quickly organizing controlled studies. The dual action of the drug may be particularly valuable because 70% of heroin abusers are also addicted to cocaine, frequently injecting them together in a concoction called a “speedball.”
Researchers are also enthusiastic about buprenorphine because it does not appear to be addictive and seems to produce no adverse side effects.
Buprenorphine is one of the first fruits of a new, $25-million program by the National Institute on Drug Abuse to develop anti-cocaine drugs. Two other promising new drugs are also being studied in humans, and as many as 28 are undergoing animal testing.
“This is exactly the kind of drug we set out to find,” said Dr. Marvin Snyder, director of preclinical research at the National Institute on Drug Abuse.
“This may be a real breakthrough,” added Dr. Forrest S. Tennant Jr., a psychiatrist who operates Community Health Projects Inc. in West Covina. “But we have to keep in mind that, unlike heroin abuse or alcohol abuse or smoking, which can be treated with a single drug, cocaine addiction will probably have to be treated with a variety of agents.”
Buprenorphine is now used as an intravenous painkiller during surgery. Researchers have recognized for several years that it has potential for treating heroin addiction. Dr. Thomas Kosten, a psychiatrist at the Yale University School of Medicine, has been studying it in addicts for that purpose for three years, comparing it to methadone, an addictive substitute for heroin that does not produce a “high.”
“We observed that it not only decreased heroin use, but that it also markedly decreased cocaine abuse,” Kosten said. Although cocaine abuse was not part of the controlled study, “We found that people receiving buprenorphine used about (one-eighth as much) cocaine as those on methadone.”
When six methadone-maintenance patients who were using cocaine heavily were switched to buprenorphine, “five stopped completely and one had a 60% reduction,” Kosten said.
Kosten and his colleagues at Yale have been conducting a controlled study of buprenorphine for cocaine abuse for six months, but they do not expect to have results for at least another year.
“I’m quite excited about the animal study because it tells us we are on the right track,” Kosten said.
The new study was conducted by Nancy K. Mello, a psychologist, and Dr. Jack H. Mendelson, a psychiatrist, at McLean Hospital in Belmont, Mass., where they operate Harvard’s Alcohol and Drug Abuse Research Center.
Mello, Mendelson and their colleagues fitted six rhesus monkeys with an implanted tube that allowed the animals to infuse themselves with cocaine by pulling on a lever. “It’s important that we don’t give cocaine to the monkeys. They administer it themselves,” Mendelson said in a telephone interview. “There is no reward for using it and no punishment if they don’t.”
The monkeys had a second implanted tube that allowed the researchers to infuse either a salt solution or a solution of buprenorphine. When the salt solution was infused, the monkeys typically administered an average of 30 cocaine injections per day, an amount per body weight comparable to that consumed by human heavy abusers.
Administration of buprenorphine caused the monkeys to simply lose interest in cocaine. By the end of 30 days of treatment, the monkeys were injecting cocaine, on average, only about twice daily. The researchers are not sure how the drug reduces the craving for cocaine.
Significantly, Mendelson said, buprenorphine did not alter the animals’ behavior or their consumption of food.
Two other medications called flupenthixol and carbamazapine also show great promise in reducing cocaine craving. Flupenthixol, which has been used in Europe for about 10 years as an antidepressant, is not available yet in the United States.
Dr. Frank Gawin, a psychiatrist at Yale, tried it on 10 cocaine users in the Bahamas who had not responded to other treatments and observed a dramatic reduction in cocaine use. The Yale group hopes to begin clinical trials with the medication within a month if they can get permission from the U.S. Food and Drug Administration.
Dr. Charles P. O’Brien, a psychiatrist at the University of Pennsylvania, has had similar, preliminary results with an anti-epileptic drug called carbamazapine, and he is beginning more rigorous double-blind studies in which neither the physicians nor their patients know what medication the drug abusers are receiving.
Researchers are also looking at new ways to administer the anti-cocaine drugs to ensure that patients continue to take them. One promising approach involves “depots,” biodegradable plastic pellets that would be injected under the skin and slowly release the medications over a period of weeks. The depots would eliminate the abuser’s need for a daily trip to a clinic to receive treatment, a factor that many feel has deterred abusers from seeking treatment.
Mendelson and others cautioned that medications alone will be insufficient in curing cocaine abuse. “There’s no magic bullet for curing drug abuse,” he said. Psychotherapy and social counseling will also be necessary.
Medications such as buprenorphine, he said, will simply provide a “window of opportunity” that will allow time for other therapies to take effect.
