April 12, 2001 -- Withdrawal symptoms and cravings for cocaine make it difficult for even the most motivated addict to kick the habit. But a medication commonly used to treat high blood pressure may offer help in that struggle by helping to relieve even those struggling with extremely severe symptoms.
In fact, the drug, known as Inderal, seems to work best in those patients experiencing very severe withdrawal symptoms, says to Kyle Kampman, MD, medical director of the University of Pennsylvania Treatment Research Center in Philadelphia.
"Patients who come into treatment with more severe withdrawal symptoms are the most difficult to treat," Kampman tells WebMD. "We know these patients are more likely to drop out of treatment and less likely to get clean. So this is the most difficult population to treat, and it is this particular population that the drug is likely to help."
In a recent study in the Journal of Drug and Alcohol Dependence, 108 cocaine-dependent patients received either Inderal or an inactive placebo pill for eight weeks. Severity of withdrawal symptoms, continued use of cocaine -- as measured by urine samples -- and length of stay in treatment were compared between the two groups.
Results showed that in general, Inderal helped reduce withdrawal symptoms but did not diminish cocaine use or improve the length of time spent in treatment.
Yet, when Kampman and colleagues looked at a smaller subgroup of patients who had the worst withdrawal symptoms upon entering the study, they found better results: Those patients receiving Inderal not only had reduced withdrawal, they stayed in treatment longer and had lower levels of cocaine in their urine.
"Only 40% of patients have a lot of withdrawal symptoms," Kampman says. "Interestingly, the patients who don't have a lot of withdrawal symptoms usually do well in treatment, whereas the patients with a lot of symptoms don't respond."
Kampman says Inderal works by blocking the effects of the hormone adrenaline, which can trigger cravings for cocaine in patients by producing a host of uncomfortable symptoms: racing heart, sweating, shakiness, and nervousness. And it is during the withdrawal period that patients are especially sensitive to the uncomfortable effects of adrenaline.
"We can block some of those symptoms to make it easier for patients to resist cravings," Kampman says.
Kampman acknowledges that the results need to be repeated in much larger trials. But if Inderal proves to be successful, it could provide a new tool to treat the most difficult patients.
"What we would hope to do is identify the 40% of patients who have the most severe withdrawal symptoms and treat them with the drug," Kampman says. "
The work with Inderal follows similar studies Kampman has done in cocaine-addicted patients using another agent known as Symmetrel. That drug is commonly used in treating influenza and has also been found useful in treating Parkinson's disease.
In a study published in the Journal of Drug and Alcohol Dependence in 1996, Symmetrel was found to have no effect on cocaine addiction. But when Kampman and fellow researchers took a second look at the drug, they found a result similar to what they found with Inderal: The patients with the most severe withdrawal symptoms had in fact benefited from Symmetrel.
Those later results were published in the December 2000 edition of the American Journal of Psychiatry.
Kampman explains that when people use cocaine, levels of a chemical called dopamine are increased in an area of the brain researchers call "the pleasure center." The effect creates a sense of euphoria -- the high that users seek.
"If you use enough cocaine then abruptly stop, the levels of dopamine decrease significantly, causing severe withdrawal," he says.
Symmetrel is believed to work by elevating levels of dopamine. By treating patients with the drug, Kampman says, the dopamine "crash" can be cushioned and symptoms of withdrawal made less painful.
In future studies, Kampman and colleagues hope to try both medications in patients who have the most severe withdrawal symptoms. Because Inderal and Symmetrel appear to have similar effects but work through different mechanisms, Kampman hopes that two drugs, used in combination, may be better than one.
"Severity of withdrawal symptoms often disrupts treatment even in patients who are motivated to stop using cocaine," says psychiatrist Bert Pepper, MD, who reviewed the report on Inderal for WebMD. "It is very clear that in cocaine dependence we are dealing with a physical addiction that is much more powerful than motivation."
Although the findings are preliminary and only apply to a small subgroup of patients, Pepper says, the problem of relapse in the early phase of treatment is so pervasive that any good news is welcome.
"In my own experience in a treatment community that had 24-hour support, we still had a high dropout rate," he says. "Anything that is helpful is important, and anything is better than nothing."
Pepper is a member of the advisory board of the federal Substance Abuse and Mental Health Services Administration. He is also executive director of The Information Exchange, a nonprofit group focusing on treatment of patients who have both mental illness and drug addiction.