Could A “Back Door” To The Brain Unlock Cure For Cocaine Addiction?

By Paul Gaita 01/22/16

Researchers may have found a drug that will help cocaine abusers quit.


A research team from the University of Cambridge in London is investigating whether a drug used to prevent acetaminophen overdose could also help individuals addicted to cocaine from habitual use of the drug.

Their study began as an investigation into the chemical and biological reasons behind cocaine addiction. “Most people who use cocaine do so initially in search of a hedonistic ‘high,'” said Dr. David Belin from the Department of Pharmacology at the University of Cambridge. “Frequent use [can lead] to addiction, where use of the drug becomes a compulsion. We wanted to understand why.”

Belin and the research team looked at earlier work conducted by fellow Cambridge professor Barry Everitt. It showed that in test rats who self-administered cocaine the dopamine released by the use of drugs initially began in the nucleus accumbens, a region in each hemisphere of the brain associated with its “reward circuit,” where activities perceived as pleasurable generate dopamine.

Over time, extended use of cocaine generated dopamine from the dorsolateral striatum, which plays a significant role in habitual behavior. More significantly, chronic exposure can alter both the prefrontal cortex, which has been associated with planning and moderating behavior, and the basolateral amygdala, which links physical stimuli to emotions. In addiction, the chain of events produces conflict between these two regions, which is solved by the use of the drug and production of dopamine from the dorsolateral striatum.

Drs. Berlin and Everitt studied the brains of test rats addicted to cocaine through self-administration of the drug and found that a pathway exists between the basolateral amygdala and dorsolateral striatum, which effectively cuts out influence from the prefrontal cortex. The pathway would feed the pleasurable memories associated with a cocaine high directly into the dopamine-producing area, leaving the individual unaware that they wanted to or even had a choice about taking the drug.

“We’ve always assumed that addiction occurs through a failure of our self-control, but now we know that this is not necessarily the case,” said Berlin. “Drug addiction is mainly viewed as a psychiatric disorder, with treatments such as cognitive behavioral therapy focused on restoring the ability of the prefrontal cortex to control the maladaptive drug use. But we’ve shown that the [region] is not always aware of what’s happening, suggesting that these treatments may not always be effective.”

Their findings led to a second study in which the test rats who self-administered cocaine were given N-acetylcysteine, a drug which had shown positive results in preventing relapse among rats in previous tests. Their own test showed that the rats that were given the drug not only lost the motivation to give themselves more drugs, but also tended to relapse at a lower rate than rats that were given a placebo. Furthermore, the rats that were given the drug showed increased activity in a gene associated with the brain’s ability to adapt and learn new skills.

N-acetylcysteine has been used in human clinical trials, where it produced mixed results. Addicted individuals who were given the drug did not stop using cocaine, but for those that were also trying to abstain from drug use, it appeared to provide some support in that regard. Further research will need to be conducted to prove the drug’s true efficacy, but as Berlin noted, “Our study suggests that N-acetylcysteine, a drug that is well-tolerated and safe, may help individuals who want to quit to do so.”

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Paul Gaita lives in Los Angeles. He has contributed to the Los Angeles Times, Variety, LA Weekly, and The Los Angeles Beat, among many other publications and websites.