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.
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.
|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|