Two-drug combination helps combat cocaine addiction

By Piriya Mahendra, MedWire Reporter

A combination of two existing pharmaceutical drugs may soon be used to treat cocaine addiction, findings from an animal study in Science Translational Medicine suggest.

George Koob (The Scripps Research Institute, La Jolla, California, USA) and co-authors found that in experiments on rats, a combination of potent µ opioid antagonist, naltrexone 0.3 mg/kg, and synthetic opioid, buprenorphine 3 mg/kg, made laboratory rats significantly less likely to take cocaine compulsively.

Koob noted in a press statement that although the two-drug combination must be proven safe and effective for people in clinical trials before being approved by the US Food and Drug Administration (FDA), the current research represents a significant advance in the field. This is because at the moment, there are no FDA-approved medications for treating cocaine addiction.

Rats who were given the two-drug combination did not exhibit the physical opioid withdrawal syndrome seen in those who were treated with buprenorphine alone. Indeed, although buprenorphine is known to be effective at helping heroin and cocaine addicts curb their addictions, the opiate itself produces dependence.

However, naltrexone at the dose used in the combination therapy did not block kappa agonist-induced analgesia, allowing limited cocaine intake while minimizing the ability of buprenorphine to produce opioid dependence.

Therefore, "combining drugs with multiple actions may be a useful approach that has not been utilized extensively," commented Koob in a press statement.

The decreased cocaine self-administration seen in rats treated with buprenorphine alone was blocked in a dose-dependent manner by naltrexone in both rats under conditions of short access (noncompulsive cocaine seeking, representing human occasional users of cocaine) or extended access (compulsive cocaine seeking, representing addicts).

The combination of the lowest dose of naltrexone used in the study (0.3 mg/kg) with buprenorphine blocked cocaine-self administration in the extended access group and not in the short access group.

The authors say this shows that only at a dosage of 0.3 mg/kg does naltrexone effectively block any dependence liability of buprenorphine, "and by extrapolation, effectively block µ opioid receptors."

The US National Institute on Drug Abuse estimated that in 2008, 1.9 million US citizens had used cocaine within the previous month. Approximately one-quarter of all drug-related emergency room visits were linked to cocaine use - amounting to 482,188 visits in 2008 alone.

Co-author Leandro Vendruscolo, also from the Scripps Institute, remarked: "These findings potentially represent a huge bridge from basic research to the establishment of a new and effective medication for cocaine addiction."

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