# Preclinical Assessment of Medications for Alcohol Abuse

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2022 · $680,409

## Abstract

Alcohol is one of the most widely used and misused drugs in the US. There is a critical need to continue to
improve AUD treatment and develop new medications to reduce alcohol use and to include nicotine co-use in
evaluations of candidate medications. This project proposes to investigate biobehavioral mechanisms
underlying alcohol and nicotine use and co-use, and to test candidate medications in two animal models
developed specifically for testing medications for alcohol abuse, and alcohol and nicotine co-use. The first
model uses a Chained Schedule of Reinforcement (CSR) procedure in which seeking and consumption occur
in the context of distinct environmental cues and behavioral contingencies to the influence of environmental
stimuli on the drive to drink and the persistence of behaviors associated with chronic drinking. Two 2 matched
groups of NHP with extensive histories of self-administration of alcohol (Alcohol group) or the non-alcoholic
beverage (Control group) will be utilized. The second model is a new Alcohol and Nicotine Concurrent Access
(ANCA) procedure in which oral alcohol and IV nicotine were concurrently available for self-administration. A
functional assessment battery provides assessment of drug side effects. Aim 1 will determine whether test
drugs reduce alcohol seeking and self-administration in the CSR under conditions of ongoing drinking and
abstinence. Aim 2 will determine whether test drugs reduce alcohol and nicotine self-administration
independently or concurrently under single drug access or ANCA procedures. Aim 3 will determine incidence
of side effects of test drugs in the functional assessment battery. Drug candidates include bifunctional and
universal opioid receptor (OR) ligands with different pharmacological profiles at OR subtypes, a universal
OR/nociception opioid peptide (NOP) receptor ligand, the cannabinoid constituent cannabidiol (CBD), the
neuropeptide oxytocin, and a nicotinic acetylcholine receptor partial agonist/antagonist varenicline. Naltrexone
will be tested as a positive control and comparator. A drug with therapeutic potential would be one that reduces
cue-maintained seeking, and decreases alcohol self-administration, and has a low side-effect profile. A drug
with therapeutic potential in alcohol and nicotine co-users would decrease alcohol self-administration without
increasing nicotine self-administration, and ideally would reduce self-administration of both drugs. Integration
these data will provide new information on the behavioral and neuropharmacological mechanisms involved in
alcohol abuse and alcohol/nicotine co-use. Comparison of dose effect functions and efficacy across models
can inform treatment strategies for optimal dosing and timing of treatment. This information will ultimately
facilitate medication development for the treatment of alcohol misuse and AUD.

## Key facts

- **NIH application ID:** 10380634
- **Project number:** 5R01AA015971-14
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Elise M Weerts
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $680,409
- **Award type:** 5
- **Project period:** 2007-09-28 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10380634

## Citation

> US National Institutes of Health, RePORTER application 10380634, Preclinical Assessment of Medications for Alcohol Abuse (5R01AA015971-14). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10380634. Licensed CC0.

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