Despite considerable efforts focusing on new drug development to reduce alcohol abuse, high rates of harmful drinking persist. Thus, developing novel therapeutics for the treatment of alcohol use disorders (AUDs) is of paramount importance. Defining novel drug therapies, using existing approved drugs for other indications, represents an economically feasible, fast approach for drug development. This training proposal is based on preclinical studies showing that acute and chronic administration of ivermectin (IVM) reduces alcohol intake and preference in mice without eliciting overt signs of toxicity. As IVM is currently FDA-approved and used by millions of humans each year for other indications, its novel employment to reduce alcohol intake opens an exciting new venue in the quest for new drugs to treat AUDs. Human laboratory models are an especially useful tool in effectively translating preclinical findings and elucidating the biobehavioral mechanisms by which pharmacotherapies may be efficacious for alcohol dependence (AD). The objective of this NRSA application is to foster my development as a clinical/ translational researcher focusing on medications development for alcoholism. The proposed study will test the hypothesis that IVM decreases alcohol consumption by evaluating the effects of this medication on an alcohol self-administration task in non-treatment seeking individuals with AD. Specifically, Aim 1 tests the hypothesis that IVM will attenuate alcohol self-administration in non- treatment seeking individuals with AD.
Aim 2 tests the hypothesis that IVM will dampen alcohol craving using cue reactivity (CR) assessment. The present study represents an important step in: 1) the implementation of IND enabling studies that will satisfy a portion of the FDA requirements for the development of IVM as a new indication for treatment of AUDs and 2) my scientific development and maturity as an independent clinical/ translational alcohol researcher.

Public Health Relevance

Current therapeutic strategies for the treatment of alcohol use disorders (AUDs) are few and, to date, have yielded only modest positive results as indicated by the continued high rates of uncontrolled heavy drinking persist. Experiments put forth in my F32 proposal represent an important step in: 1) the implementation of IND enabling studies that will satisfy FDA requirements for the development of ivermectin (IVM) as a new indication for treatment of AUDs and 2) my scientific development and maturity as an independent clinical/ translational alcohol researcher.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32AA023449-02
Application #
8924767
Study Section
Health Services Research Review Subcommittee (AA)
Program Officer
Ryan, Megan
Project Start
2014-08-19
Project End
2016-08-18
Budget Start
2015-08-19
Budget End
2016-08-18
Support Year
2
Fiscal Year
2015
Total Cost
$52,406
Indirect Cost
Name
University of California Los Angeles
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Cservenka, Anita; Yardley, Megan M; Ray, Lara A (2017) Review: Pharmacogenetics of alcoholism treatment: Implications of ethnic diversity. Am J Addict 26:516-525
Yardley, Megan M; Ray, Lara A (2017) Medications development for the treatment of alcohol use disorder: insights into the predictive value of animal and human laboratory models. Addict Biol 22:581-615
Yardley, Megan M; Mirbaba, Michael M; Ray, Lara A (2015) Pharmacological Options for Smoking Cessation in Heavy-Drinking Smokers. CNS Drugs 29:833-45