Research ArticleAddiction

A Combination of Buprenorphine and Naltrexone Blocks Compulsive Cocaine Intake in Rodents Without Producing Dependence

Science Translational Medicine  08 Aug 2012:
Vol. 4, Issue 146, pp. 146ra110
DOI: 10.1126/scitranslmed.3003948

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Cocaine Addiction: Three Drugs Are Better Than One

Some drug addictions can be treated with other drugs. Methadone, for example, is given to people addicted to heroin, where it acts at opioid receptors to decrease withdrawal symptoms and, at higher doses, block the euphoric effects of heroin—allowing addicts to successfully wean themselves off heroin. Now, Wee and colleagues report that a particular combination of drugs (a synthetic opioid and a μ opioid antagonist) may be able to interrupt the cycle of behaviors that underlie cocaine addition.

Rats can be induced to show cocaine addiction-like behavior, compulsively pushing a lever that injects the drug directly into their bloodstream. Simultaneously giving them a synthetic opioid such as buprenorphine, which acts at μ and κ opioid receptors, inhibits the addictive process and blocks the compulsive drug taking—but at a cost. The animals become dependent on buprenorphine itself, abolishing any positive effect of preventing the cocaine addiction. This approach is also not a good one to use in humans. To get around this problem, the authors of this paper added another agent to the mix. Along with buprenorphine, they gave the rats different doses of naltrexone, an antagonist at μ opioid receptors. At low doses of naltrexone, the drug combination interrupted the cocaine addiction cycle but did not produce dependence on buprenorphine itself.

The lesson from these studies is that appropriate dosages of drugs with the correct specificities can profitably manipulate the powerful opiate system in the brain—to the advantage of the physician trying to help addicted patients. The winning combination for treating cocaine addiction described in this paper will need to be tested in people, but the pharmacology is likely to be similar. In this case, three drugs may be better than one.