For some alcoholics, booze provides an addictive thrill. For others, alcohol is a balm for stress and anxiety. A new study identifies a drug that may be particularly effective for treating the latter group. The drug, which blocks receptors for a neurotransmitter involved in stress responses, substantially reduced cravings in a group of rehabilitating alcoholics.
The most widely used drug for treating alcoholism is naltrexone, which blocks feel-good opioid receptors in the brain. But recent research has found that naltrexone tends to work best for the roughly 20% of alcoholics who start drinking early--before age 25--and who get hooked on alcohol because of the kick they get from drinking, says Markus Heilig, a researcher at the U.S. National Institute on Alcohol Abuse and Alcoholism in Bethesda, Maryland. The drug is less effective for the other 80% of alcoholics, who typically develop alcohol dependency later in life and drink mainly to relieve anxiety. Heilig and colleagues hypothesized that drugs that blunt stress responses in the brain might be more useful for treating this more common kind of addiction.
In a paper published online today in Science, the team describes experiments with a drug that blocks a receptor for substance P, a neurotransmitter involved in signaling pain and stress. The drug, known as LY686017, had proved safe in previous clinical trials for depression but hadn't been effective enough to continue development, Heilig says. The researchers selected 50 volunteers, all recovering alcoholics who'd scored high on a questionnaire that measures anxiety, and gave half a daily dose of LY686017; the other half got a placebo pill.
Those who got the drug scored consistently lower on a standard questionnaire that gauges alcohol cravings over the course of the monthlong experiment. To examine the volunteers' resolve under stress, the researchers staged mock interviews with three stern-faced assistants in white lab coats. Each volunteer had to give a 5-minute presentation to convince the "committee" that he or she was the perfect person for a dream job and then had to do 5 minutes of difficult mental arithmetic. After this ordeal, volunteers were given a small container of their favorite tipple to handle and sniff but not drink. In the placebo group, blood tests revealed high levels of the stress hormone cortisol, and questionnaires exposed serious alcohol cravings. Cortisol levels and cravings were substantially lower in the volunteers who were taking the drug.
"I think it is an exciting story," says neuroscientist Selena Bartlett of the Ernest Gallo Clinic and Research Center at the University of California, San Francisco. The work meshes well with a growing realization that people become dependent on alcohol for different reasons, she says. "It feels like we're heading for a sea change for new therapies for alcoholism."
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