A New Treatment for Alcoholism?

By Suzanne Wu

Ivermectin therapy could enable alcoholics to consume a drink or two without losing control.

Daryl Davies is shedding new light on one of the key molecular culprits of alcoholism.

Davies co-directs the Alcohol and Brain Research Laboratory at USC, the only lab in the world focused on how alcohol affects a little-known family of brain molecules: purinergic, or P2X, receptors.

“In our group, almost every researcher has seen first-hand the devastation caused by addiction,” says the associate professor of clinical pharmacy at the USC School of Pharmacy. “It’s how I became interested in alcohol research. Why can’t we cure alcoholism?”

Beginning a decade ago, Davies – who still has the same office since his days as a doctoral student at USC – made the first in a series of breakthrough discoveries.

Notably, he and longtime collaborator Ronald Alkana, professor of pharmacology and pharmaceutical sciences at USC, found that P2X4, a subtype of P2X, contains an ion “gate” that stops working when exposed to ethanol, the type of alcohol found in alcoholic beverages.

If flooded with enough ethanol over time, the ion gate actually mutates and stops working altogether.

“You know the saying, ‘Once an alcoholic, always an alcoholic’? It’s true,” Davies says. When exposed to enough alcohol, the brain’s molecular structure can change – permanently.

By happenstance, Davies’ lab then found another chemical, ivermectin, which works on the same ion gate as ethanol. Initially, Davies and his colleagues were using ivermectin to isolate P2X4 molecules from other subtypes, say, P2X3.

An anti-parasitic used worldwide on humans and animals, ivermectin is commonly found in the United States as an additive to flea and tick medication applied to the necks of cats and dogs.

The substance appears to significantly inhibit the effects of alcohol on P2X4 receptors. In a flurry of research released this year, a collaborative team of USC researchers showed that alcohol-dependent mice drink much less – about 50 percent less – when taking ivermectin.

Davies doesn’t yet know why ivermectin limits alcohol intake in mice or why it helps signal that it’s time to stop drinking. Using it to treat alcohol abuse in humans would be a departure from abstinence-based models of addiction treatment. Of the three main drugs currently approved for treating alcohol dependence, all try to make alcohol undrinkable or undesirable. All, even in conjunction with therapy, have a success rate of less than 10 percent.

Ivermectin therapy could enable alcoholics to consume a drink or two, without the compulsion to drink to the point where they start to lose control, according to Davies.

That ivermectin already is approved for human use is critical, and not only to help bring the drug to market relatively quickly and inexpensively. Its long history of ingestion, particularly in sub-Saharan Africa, means that ivermectin is unlikely addictive itself, Davies says.

With Nicos A. Petasis, the Harold E. and Lillian M. Moulton Professor of Chemistry at the USC Dornsife College of Letters, Arts and Sciences, and Stan Louie, associate professor of clinical pharmacy at the USC School of Pharmacy, Davies and Alkana now are working on developing an entirely new class of drugs based on ivermectin’s molecular structure.

“If there was already a drug that was 95 percent effective, I might not be studying ivermectin. I might not even be in the alcohol field,” he says. “The funding for alcoholism research hasn’t caught up with the magnitude of the consequences of not finding a cure.”