A Combo of Existing Drugs Could Treat Cocaine Addiction

Two drugs currently used to treat heroin and prescription painkiller addiction may work together to fight cocaine as well without causing dependence themselves, according to a new study in rats.

A clinical trial in humans is currently enrolling patients, and if future research is successful, the new drug combination buprenorphine plus naltrexone could be the first medication developed for the treatment of cocaine addiction. The drug would likely work for methamphetamine and other stimulant addictions, too.

The new research originated with Dr. Nora Volkow, director of the National Institute on Drug Abuse, who asked George Koob of the Scripps Institute in California to lead the study. I had been intrigued by the clinical trials showing that when you use buprenorphine, use of cocaine goes down significantly, says Volkow, referring to previous studies of people with heroin addiction who reduced their use of cocaine while being treated with buprenorphine.

But buprenorphine (Suboxone, Subutex) is an opioid, which means that it can cause physical dependence and has the potential for misuse. So, for people who use cocaine but arent already addicted to heroin or a similar drug, buprenorphine could make their problem worse. The last thing addiction treatment providers want to do is add a new class of drug to a clients repertoire.

That complication precluded the possibility of testing buprenorphine on its own in cocaine addicts. It was scientifically plausible, however, to think that using it in combination with another medication that blocks some of its opioid effects could prevent this problem. As it turns out, naltrexone (reVia, Vivitrol) fits the bill.

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Buprenorphine itself is a marvel of multiplicity. At low doses, it acts like an opioid, cutting physical and emotional pain and reducing anxiety by activating a class of opioid receptors, known as mu receptors. At high doses, it has the opposite effect: preventing opioid-like action and inducing withdrawal symptoms rather than relief. Thats what makes it an especially safe drug for maintenance of people with opioid addictions. But buprenorphine has another action as well: it blocks the kappa opioid receptor, a target that has long intrigued pharmacologists because it seems to be one of the brakes on the pleasure-producing dopamine system.

When people repeatedly take drugs particularly stimulants like cocaine and methamphetamine the brain releases excessive amounts of dopamine. This triggers a feedback loop: it overactivates kappa opioid receptors, which in turn shuts dopamine down. Now its payback time, says Koob, because your brains pleasure pathways conform to an austerity plan, getting increasingly stingy with the joy juice.

The distress and dysphoria associated with rising kappa activation seem to be what drives addicts to seek more drugs, in a vain attempt to feel better. Ultimately, however, that makes matters worse as the feedback dials the pleasure volume down even further. I call it pharmacological Calvinism, Koob says, noting that while the human brain is wired to enjoy everyday pleasures, frequent drug use triggers the stress system, which prevents the party from lasting forever.

The reward systems sensitivity decreases profoundly and that leads the addicted person to feel very little pleasure from almost any reward, including the drug itself, Volkow says.

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A Combo of Existing Drugs Could Treat Cocaine Addiction