Drug to Curb Smoking Also Cuts Alcohol Dependence

July 09, 2007
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A drug already approved for nicotine addiction also curbs alcohol dependence, a new animal study shows. One dose alone cut drinking in half. The finding is particularly encouraging, the researchers say, because the animals did not turn to drinking in excess after the drug was stopped, a common pattern when people take current drugs to curb alcohol consumption.

In addition, the drug did not kill appetite, which the most effective drug to curb alcohol dependence does.

In the study, rats had access to unlimited amounts of alcohol. Under these conditions, they steadily increased their alcohol intake over several months. But the first day they received the drug, they cut their drinking in half. They received the drug every other day for a week, and during this period, maintained their lower drinking level. When the drug was discontinued, they returned to their previous level -- but no higher.

The research is being published online by "The Proceedings of the National Academy of Sciences." The paper goes online the week of July 9.

The study was led by Selena Bartlett, director of the Preclinical Development Group at the UCSF-affiliated Gallo Clinic and Research Center.

Only three drugs are available to treat alcohol dependence, and even the most effective one, naltrexone, reduces appetite as it cuts alcohol use, Bartlett says. The new drug is called varenicline (brand name Chantix).

"The biggest thrill is that this drug, which has already proved safe for people trying to stop smoking, is now a potential drug to fight alcohol dependence," Bartlett says. "Alcoholism takes a tremendous toll, and so few drugs are available to counter it."

Bartlett notes that 85 percent of alcoholics smoke, so if clinical trials confirm varenicline is effective against alcoholism, physicians can prescribe the drug to treat both conditions. Bartlett's team, in collaboration with Markus Heilig at the National Institute on Alcohol Abuse and Alcoholism, is now planning clinical trials of the drug's effectiveness against alcohol craving and dependence.

Varenicline was developed by the pharmaceutical company Pfizer to counter nicotine addiction. It has been approved by the Food and Drug Administration and has been available for about a year. Pfizer currently markets it to physicians.

The drug probably reduces both drinking and smoking, Bartlett says, because nicotine and alcohol trigger the same "reward circuitry" in the brain. Scientists have known for 25 years that consumption of either substance activates receptors on neurons within this circuitry, deep in the brain, an area known as the VTA -- the ventral tegmental area. This action is thought to release the "feel good" neurotransmitter dopamine into another part of the circuitry, the nucleus accumbens. The dopamine release occurs in response to most addictive drugs, including morphine, cocaine, nicotine and alcohol, Bartlett says.

The receptor involved is called the neuronal nicotinic acetylcholine receptor. Nicotine binds directly to it, while alcohol induces the release of another neurotransmitter, acetylcholine, which then activates the receptor. Either way, dopamine is released.

The drug also binds to the receptor, and so prevents its activation by nicotine or alcohol. Researchers think of nicotine as a "gateway drug" the first drug of abuse most people try, Bartlett said. This experience may drive the brain's reward system toward addiction.

The scientists carried out three alcohol-drinking studies with rats. In the key study, the animals had access to alcohol every other day over a period ranging from two to four months. They steadily increased their alcohol intake every day it was available -- an indication of alcohol dependence.

The intermittent access to alcohol is thought to produce stress as a result of the days when the alcohol is not present and the animals are in withdrawal. It models the early stages of alcohol dependence in people in which abstaining for a day or more induces the sensation of withdrawal, which then leads drinkers to consume more, eventually leading some to addiction, Bartlett says.

Since its safety has already been established, varenicline can be put to clinical use much more quickly if it is found effective in people, Bartlett says. She hopes that the research will prompt more studies to help people gain control of alcohol dependence.

"Treatments for alcoholism today are like those for schizophrenia in the 60s." People don't talk about it. There are very few treatments, and most drug companies are not interested in it.

"It's a disease. If you've inherited a gene variant, or if some other cause leads you to alcohol dependence, it should be treated -- like any disease."

The Preclinical Development Group that Bartlett leads at the UCSF-affiliated Gallo Center was established two years ago to develop new treatments and bridge the gap between research and clinical treatment. The team is pursuing other promising treatments, as well, Bartlett says.

The effort is part of UCSF's focus on "translational" research, aimed at speeding the application of basic science discoveries to better diagnostics and treatments. The University's effort received a major endorsement in 2006, when it received funding from the National Institutes of Health for establishment of a Clinical and Translational Science Institute.

First author on the paper is Pia Steensland, a postdoctoral scientists working with Bartlett. Co-authors are Jemma Richards, also a postdoctoral fellow with Bartlett; Jeffrey Simms, a staff research associate; and Joan Holgate, a junior specialist, all at the Gallo Clinic and Research Center.

The research was supported by the State of California for Medical Research on Alcohol and Substance Abuse.

The Ernest Gallo Clinic and Research Center (Gallo Center) is one of the world's preeminent academic centers for the study of the biological basis of alcohol and substance abuse. Gallo Center discoveries of potential molecular targets for the development of therapeutic medications are extended through preclinical and proof-of-concept clinical studies. The Center is part of the UCSF Department of Neurology.

UCSF is a leading university that advances health worldwide by conducting advanced biomedical research, educating graduate students in the life sciences and health professions, and providing complex patient care.

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