Cocktail of Meds Could Treat Coke Addiction

By Maia Szalavitz 08/09/12

Combining buprenorphine with naltrexone produces highly promising results in a rat study.

Not only rodent coke-fiends might benefit.
Photo credit: Jay Kusnetz

A cocktail of FDA-approved medications—including the opioid buprenorphine (Suboxone, Subutex)—could treat cocaine addiction without producing physical dependence, according to a new rat study, published in Science Translational Medicine. The trick is adding the opioid-blocking drug naltrexone, which can preserve the anti-coke effects of buprenorphine without producing a high—or leading to the physical dependence that develops with daily opioid use. As noted in

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. That’s 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 “it’s payback time,” says [lead researcher] George Koob [of the Scripps Institute], because your brain’s pleasure pathways conform to an austerity plan, getting increasingly stingy with the joy juice.

But the study found that in the right dosage, adding naltrexone to buprenorphine preserves the kappa blocking effect of the drug, without the high and addiction potential associated with the mu receptor—at least in rats. A clinical trial in patients with both cocaine and heroin addiction is currently recruiting. (A clinical trial is one of the best places to get top notch addiction care: even if you wind up in the control group, you'll still get treatment based on the best available evidence). If the combo proves effective, expect trials in people with cocaine and amphetamine addictions that don’t involve opioids. Since both drugs are already approved, providers could use them in treatment as soon as the best dosing is discovered. But using two separate pills might prove tricky if addicted people decide to skip the naltrexone to get high on buprenorphine. Not that it would be a very good high: the version used in addiction treatment has abuse deterrent drugs in it that mean it can only be taken orally, although it could have some effect and daily use without the naltrexone would produce dependence. The drug cocktail could also potentially help depression and chronic pain, both of which may involve reduced pleasure caused by an overactive kappa opioid system. 

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Maia Szalavitz is an author and journalist working at the intersection of brain, culture and behavior.  She has reported for Time magazine online, and is the co-author, with Bruce Perry, of Born for Love: Why Empathy Is Essential—and Endangered, and author of Help at Any Cost: How the Troubled-Teen Industry Cons Parents and Hurts Kids. You can find her on Linkedin and  Twitter.