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Experimental Drug Dampens Alcohol Craving

Blocking stress-related circuits in the brain can reduce the desire for alcohol in people who are trying to stop drinking, a small clinical study has found. The discovery may provide a new approach for developing alcoholism treatments.

Stress is known to trigger alcohol craving and relapse in alcoholics who've stopped drinking. While some current alcoholism medications work by dampening alcohol's pleasurable effects or even causing nausea when a person drinks, a team of researchers at NIH's National Institute on Alcohol Abuse and Alcoholism (NIAAA) decided to focus on reducing the brain's stress response as a potential treatment.

In research reported online on February 14, 2008, in Science Express, NIAAA Clinical Director Markus Heilig and colleagues from NIH, Lilly Research Laboratories and University College in London found that a brain molecule known as the neurokinin 1 receptor, or NK1R, appears to play a central role in stress-related drinking.

The researchers first showed that interfering with NK1R can affect alcohol consumption in animals. The scientists created genetically engineered mice that lacked NK1R. When given free access to both water and alcohol for 2 months, the NK1R-deficient mice consumed far less alcohol than normal mice with fully functional NK1R.

Next, the scientists conducted a small experimental study in humans with a drug designed to block NK1R. The study involved 50 recovering alcoholics. All had recently stopped drinking and had high levels of anxiety. Half received daily doses of the experimental drug, while the other half received a placebo. All were hospitalized throughout the month-long study.

Alcohol craving was greatly reduced for those taking the drug, and their overall wellbeing was enhanced. Using functional brain imaging, the researchers showed that the medication seemed to reduce the brain's exaggerated response to negative stimuli—like disturbing photographs—typically seen in alcoholics. The drug also seemed to restore brain responses to pleasurable stimuli.

"These findings advance our understanding of the link between stress and alcohol dependence and raise the prospect of a new class of medications for treating alcoholism," said NIAAA Director Dr. Ting-Kai Li.

The researchers note that further studies are needed to determine how effective NK1R-blocking drugs might be in treating alcohol addiction. They point out that their small study looked only at highly anxious alcoholics who were hospitalized. It's unclear if NK1R-blocking drugs would have similar effects on non-anxious individuals trying to stop drinking in a real-world setting.