UCSF Researchers Make Headway with Potential Alcoholism Drug

In a groundbreaking drug study using mice and rats, two members of UCSF’s Neurology department have tapped into a potential new treatment for alcoholism in humans. Robert Messing, MD, professor of neurology and associate director of UCSF’s Ernest Gallo Clinic and Research Center, and Philip Newton, PhD, assistant adjunct professor of neurology and associate investigator at the Emeryville-based research center, tested an existing drug that blocks the N-type calcium channel, a molecular switch in the brain that enables alcohol to produce its intoxicating effects. Currently, N-type calcium channel inhibitors are being used in clinical trials for the treatment of chronic pain. However, Messing, Newton and their fellow investigators wanted to see whether such a drug would have an effect on alcohol consumption and levels of intoxication. What they found was striking: Mice who received the drug no longer sought out the places where they had previously been given alcohol, and rats also drank less alcohol after consuming the drug. The drug also appeared to curtail stress-induced drinking, so often a major roadblock on the road to recovery from alcoholism. “One of the most troubling symptoms of alcoholism is the high rate of relapse, with stress being one of the leading causes,” Newton said. “Rats, too, will seek out alcohol in times of stress – but not, we found, when treated with [the calcium channel blocker].” In addition to suppressing the desire to drink, the drug substantially reduced drunkenness in mice over a wide range of alcohol doses. The findings of the study, which appears in the Nov. 5 issue of the Journal of Neuroscience, were “a bit of a surprise,” said Newton, who served as lead author. “We didn’t expect the drug to work quite as well as it did,” he said. “It was sort of a best-case scenario.” Alcohol abuse and dependence affect roughly 17.6 million Americans and cost the country approximately $184 billion per year in legal and medical fees and lost wages, according to the National Institute on Alcohol Abuse and Alcoholism. To date, only three drugs have been approved for alcoholism treatment in the United States, and their success rate has been moderate at best. Noting the “unique and desirable effect profile” of calcium channel blockers, Messing said he hoped his team’s work would prompt drug companies and other researchers to recognize such drugs as promising alternatives to current treatment methods. In the meantime, Messing and Newton are moving full speed ahead with their own research. They are in the process of finishing a paper on a calcium channel blocker approved for use in the treatment of epilepsy, and they have also applied for a grant to test a similar drug used to treat migraines. In a phone interview the day before the study’s publication, Messing was careful not to appear overconfident, despite the potentially far-reaching implications of the findings. “We sound a bit sedate because we’ve been down this road with many other drug targets,” he said of himself and Newton. “But this one looks pretty cool.”