Advancing medications development is a critical objective in reducing health and societal burdens associated with alcohol use disorder (AUD. Recently, priority has been placed on human laboratory paradigms as an efficient and cost-effective method for screening new candidate therapies. In addition to the efficiency of this approach, an advantage of human laboratory screening trials is the ability to examine medication effects on alcohol-related behaviors analogous to those studied in animal studies (e.g., operant responding, self- administration), maximizing correspondence between human and animal studies. Animal studies have implicated histamine H3 receptors in alcohol intake, motivation, and reinstatement. For example, alcohol consumption was reduced in mice lacking the H3 receptor, and H3 antagonists decreased alcohol intake and effort to obtain alcohol in an animal model of alcohol dependence. Recently, novel H3 antagonists have been developed, representing potential therapies for the indication of alcohol use disorder. The purpose of the present proposal is to conduct an initial trial of a new H3 antagonist medications in humans with AUD. Specifically, this project proposes a randomized medication screening trial with human laboratory components. Non-treatment-seeking participants with AUD will participate in medication and placebo treatment phases in a randomized, counter-balanced fashion, with laboratory sessions occurring at the conclusion of each phase. To maximize experimental control, the laboratory component of this study will utilize intravenous (IV) alcohol administration paradigms. Additionally, to maximize comparability with animal models, laboratory paradigms will be analogous to those used in animal studies of H3 antagonists. This project will allow for the first human medication screening trial of H3 antagonist treatments in participants with AUD. Our long-term goal is to facilitate the translation of basic science discoveries in clinical validation studies by establishing an efficient process for conducting human screening studies of candidate therapies for AUD.

Public Health Relevance

Animal studies have shown that histamine H3 antagonists may be effective in reducing alcohol consumption and relapse, suggesting that H3 antagonists are candidate medications for the treatment of alcohol use disorder. The aim of this study is to conduct a medication screening study to examine whether a novel H3 antagonist influences alcohol consumption in participants with alcohol use disorder. This study will provide initial human data concerning the potential efficacy of H3 antagonists for the indication of alcohol use disorder.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AA026035-02
Application #
9786647
Study Section
National Institute on Alcohol Abuse and Alcoholism Initial Review Group (AA)
Program Officer
Falk, Daniel Evan
Project Start
2018-09-20
Project End
2020-08-31
Budget Start
2019-09-01
Budget End
2020-08-31
Support Year
2
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Centre for Addiction and Mental Health
Department
Type
DUNS #
207855271
City
Toronto
State
ON
Country
Canada
Zip Code
M5S2S1