Craving, the almost irresistible urge to use drugs, is one of the most vexing problems associated with drug addiction. Craving is the result of changes that drugs cause in the brain and may be triggered by physical discomfort associated with abstinence from the drug. Craving also may be triggered by external, environmental factors, such as the sights, sounds, and social situations associated with drug use. In this "cue-induced" craving, the urge to use drugs often is powerful enough to cause a relapse to drug abuse months or even years after a person has stopped using drugs.
Twenty-three patients were asked to rate the intensity (on a scale ranging from 0 to 100) of their craving for cocaine and their feeling of anxiety after viewing and handling cocaine-related objects like those shown in the background of the graph. Patients who received mecamylamine before exposure to the objects reported significantly less anxiety and craving for the drug.
Dr. Malcolm Reid, a NIDA-supported researcher at the New York University School of Medicine and the New York Veterans Affairs Medical Center in New York City, has found that mecamylamine-a medication that blocks the rewarding effects of nicotine-can reduce cue-induced craving in patients addicted to cocaine and may help these patients avoid relapse.
In earlier research, Dr. Reid found that nicotine significantly increased cue-induced craving for cocaine in addicted patients who also smoked tobacco. "This finding suggested that a medication like mecamylamine, which blocks some of nicotine's effects in the brain, might also reduce the cue-induced craving that nicotine causes," Dr. Reid says.
Dr. Reid recruited 23 cocaine-addicted patients, 20 men and 3 women with an average age of 40, from outpatient drug addiction treatment programs. All patients were regular cigarette smokers and had used crack cocaine within the last 3 months. Patients were instructed to abstain from tobacco for at least 1 day and from cocaine for 2 days before participating in the craving test sessions. Abstinence was verified by laboratory tests.
The participants were shown a series of neutral cues as well as cocaine-related cues. During each test session, participants first viewed the neutral cues, including videotaped images of pine cones and seashells, and then handled rocks, pine cones, and seashells and smelled a fragrant spice. Participants then completed a survey that asked them to describe their mood-for example, "anxious," "nervous," or "irritated"-and rate the intensity of their desire to use cocaine and the likelihood that they would use cocaine if it were available. Following exposure to neutral cues, participants were randomly given either mecamylamine or placebo. Two hours later they were exposed to a series of cocaine-related cues, which included videotaped scenes in which actors simulated purchasing and smoking crack cocaine and scenes of actual crack smoking. The participants then handled drug paraphernalia and a substance that looked like crack cocaine, and smelled a crack pipe that had been treated with an artificial residue with the same aroma as crack cocaine. As before, they rated their mood and desire to use cocaine. The procedure was repeated 2 to 3 days later, with patients who had received mecamylamine during the first session receiving placebo during the second session, and vice versa.
"All the patients reported that they felt an increased craving for cocaine after the cocaine-related cue sessions, but those who received mecamylamine reported less anxiety and significantly less intense cocaine craving-only half as strong on average-than did the patients who received placebo," Dr. Reid says. "In addition, the patients who received the medication reported less intense symptoms of tobacco withdrawal prior to being exposed to cocaine-related cues."
"Those who received mecamylamine reported significantly less intense cocaine craving-only half as strong on average."
The success of mecamylamine in reducing both cue-induced craving for cocaine and the rewarding effects of nicotine has important implications in treatment. Epidemiologic studies show that smoking is more prevalent among cocaine-addicted persons than in the general population and that cocaine-addicted smokers begin using cocaine at an earlier age and use it more frequently than cocaine-addicted nonsmokers. "In earlier studies we found that nicotine may intensify cue-induced craving for cocaine, which can make it difficult for cocaine addicts to stop using the drug. We now know that mecamylamine may reduce cue-induced cocaine craving and it does so even when subjects do not have nicotine in their system," Dr. Reid says.
"Previous clinical and preclinical studies have suggested that mecamylamine has therapeutic potential in the treatment of smoking cessation and alcoholism," Dr. Reid notes. "Our current findings indicate it could also play an important role in reducing the risk of relapse for patients in treatment for cocaine addiction." To further investigate this possibility, Dr. Reid is now conducting a clinical trial of mecamylamine treatment of cocaine addiction at the New York Veterans Affairs Medical Center.
Reid, M.S.; Mickalian, J.D.; Delucchi, K.L.; Hall, S.M.; and Berger, S.P. An acute dose of nicotine enhances cue-induced cocaine craving. Drug and Alcohol Dependence 49:95-104, 1998.
Reid, M.S.; Mickalian, J.D.; Delucchi, K.L.; and Berger, S.P. A nicotine antagonist, mecamylamine, reduces cue-induced craving in cocaine-dependent subjects. Neuropsychopharmacology 20(3):297-307, 1999.