Notice of Intent to Publish a Funding Opportunity Announcement for Mechanisms of Tolerance (R21/R33 - Clinical Trial Not Allowed)

Notice Number: NOT-AA-17-017

Key Dates
Release Date: November 29, 2017  

Estimated Publication Date of Announcement: Winter 2017
First Estimated Application Due Date: April 2018
Earliest Estimated Award Date: October 2018
Earliest Estimated Start Date: October 2018

Related Announcements

Issued by
National Institute on Alcohol Abuse and Alcoholism (NIAAA)


The National Institute on Alcohol Abuse and Alcoholism intends to promote a new initiative by publishing a Funding Opportunity Announcement (FOA) to solicit applications for research on mechanisms underlying sensitivity and tolerance in the development of alcohol use disorders.

The intent of this FOA is two-fold: (1) develop new hypotheses about key factors and pathways in sensitivity and tolerance to alcohol, and (2) develop a common framework of mechanisms underlying the development of tolerance and the progression to alcohol dependence. These objectives will be accomplished with a Phased Innovation (R21/R33) mechanism, in which secondary data analysis or pilot studies can occur during the R21 phase, and research testing the hypotheses can be expanded in the R33 phase.

This Notice is being provided to allow potential applicants sufficient time to develop meaningful collaborations and appropriate projects. 

The FOA is expected to be published in Winter 2017 with an expected application due date in Spring 2018.

This FOA will utilize the R21/R33 activity code, clinical trial not allowed. Details of the planned FOA are provided below.

Research Initiative Details

This Notice encourages investigators with expertise and insights into this area of alcohol use and dependence to begin to consider applying for this new FOA. While there is a scarcity of studies directly addressing mechanisms of tolerance, alcohol research has an abundance of reports and data from subjects with AUD or alcohol dependence. The pathway to dependence likely included the development of tolerance, and particularly in animal models, data were collected to meet criterion of dependence. The data gathered from the alcohol exposure paradigms, including changes in blood alcohol concentrations, and changes in behavioral and physiological measurements with subsequent alcohol intake, may fill the gap in understanding the heterogeneity in levels of response (sensitivity) and tolerance to alcohol. Therefore, the R21/R33 mechanism provides the opportunity re-examine previous data with the focus on differential responses and tolerances to alcohol.

The goal of the R21 phase of the FOA is to develop new hypotheses and common experimental framework(s) between human - animal studies and animal-animal studies to characterize the sensitivity and tolerance (including individual variations) and alcohol use and dependence. Most animal studies of alcohol intake include measurements of blood alcohol concentration, in addition to the behavioral or physiological measurements. Re-analysis of these data, through the lens of understanding sensitivity and tolerance, has the potential to provide preliminary data to develop and test new hypotheses about the roles of sensitivity and tolerance in the development of dependence and AUDs. In addition, collaborative investigations combining expertise in experimental alcohol intake paradigms, transgenic animal models, and translational human-animal studies will be encouraged and these investigators should consider applying for this opportunity.

Studies of cross-tolerance effects of alcohol with other drugs of abuse or multiple substances are not within scope of the new announcement.

Studies of the genetics of tolerance may also be appropriate the Genetics of Tolerance R01, NOT-AA-17-016


Please direct all inquiries to:

Elizabeth Powell, PhD
National Institute on Alcohol Abuse and Alcoholism (NIAAA)