Alcohol use disorders constitute a major unmet medical need – affecting 18 million people and causing 100,000 annual deaths in the United States – and current therapeutic approaches have had only limited and non-durable success in treating them.

Associate Professor Daryl Davies, PhD,  hopes to develop an effective treatment for these disorders through two new studies, one focusing on repurposing the FDA-approved drug ivermectin – currently used as an antiparasitic medication – and the other examining the role of specific receptors on alcohol intake. His novel approaches to dealing with alcohol use disorders have earned him a wide range of new funding.

Daryl Davies, PhD

This includes financial support from the Southern California Clinical and Translational Science Institute (SC CTSI) at USC and CHLA, which awarded him a pilot grant for the project titled, “Repositioning Ivermectin for the Treatment of Alcohol Use Disorders/First in Human Studies,” as well as a second, interrelated grant from the Clinical and Translational Science Institute at UCLA titled “Repositioning Ivermectin for the Treatment of Alcohol Use Disorders,” that was awarded to his UCLA clinical partner, Dr. Lara Ray, for which he will serve as key personnel. The SC CTSI grant comes in the form of a $50,000 2013 Multidisciplinary Research Pilot Award, and UCLA’s grant is a $30,000 2013 Pilot Award from the Clinical Research Center.

“We recently reported that ivermectin significantly reduced alcohol intake in mice,” says Davies. “The specific aims of this multidisciplinary SC CTSI pilot project will provide key clinical and preclinical evidence that ivermectin can be repositioned as a novel therapeutic agent to treat alcohol use disorders.” 

The funding will be used to enroll ten alcohol dependent individuals into a pilot safety and efficacy trial of ivermectin.

“The SC CTSI award allows us to do 10-person clinical trial at UCLA, while UCLA’s portion of the funding is important because it allows us to use their onsite clinical trials unit,” explains Davies of his collaborative grant.

“We are excited to support this translational research. It has great potential to repurpose an existing generic medication to help treat a very common and serious problem – alcohol abuse. I am very happy we can work with our colleagues in the CTSI at UCLA to make this research happen,“ said Tom Buchanan, MD, SC CTSI director and vice dean for research at the Keck School of Medicine of USC.

Ray agrees and added “The translation of animal findings to humans is key to developing treatments that will ultimately improve the quality of life of patients suffering from alcoholism. My laboratory is committed to developing medications for addiction and we are excited about our partnership with Davies’ group to study Ivermectin.”

The clinical study will examine the safety of combining ivermectin with moderate doses of alcohol, and will test whether it reduces the reinforcing effects of alcohol and alcohol craving. The study also aims to set the stage for a Phase II study, in which a preclinical team at USC will test the hypothesis that longer term, oral administration of ivermectin reduces alcohol intake with tolerable and limited side effects.

Davies will be working with several collaborators on the project. Within USC, he will be working with Ron Alkana, Kathy Rodgers, Stan Louie and Eunjoo Pacifici, and at the Children’s Hospital of Los Angeles, he will be working with Michael Neely.  His UCLA collaborators include Lara Ray, Daniel Roche and Karen Miotto.

“The use of ivermectin as a therapeutic agent to reduce alcohol consumption represents a novel use of the drug, and opens an exciting new venue in the search to identify new ways to treat alcohol use disorders,” says Davies.

In addition to these awards, the National Institutes of Health recently awarded Davies a three-year grant for $856,585 for the project, “Regulation of Alcohol Intake by Purinergic P2X4 Receptors.” Studies from this funded project will investigate the role of P2X4 receptors in the regulation of alcohol intake. 

The grant will build on previous work in the Davies laboratory, which demonstrated that ivermectin selectively and positively modulates P2X4 receptors, and blocks the inhibitory effects of alcohol on P2X4 receptor function.  Results from the NIH-funded work will provide significant new mechanistic insight into how P2X4 receptors affect alcohol intake. 

“Findings from this work should lead to new opportunities focusing on the development of novel therapeutics for the prevention and treatment of alcohol use disorders,” says Davies.

Related funding sources:

• Funding by SC CTSI at USC and CHLA
• Funding by CTSI at UCLA