# Probenecid as pharmacotherapy for alcohol use disorder

> **NIH NIH R21** · BROWN UNIVERSITY · 2021 · $192,969

## Abstract

PROJECT SUMMARY
Testing pharmacotherapies in controlled human alcohol laboratory paradigms is critical for the identification and
development of therapeutic interventions to prevent alcohol use disorder (AUD). Thus, for this proposal, an
alcohol administration procedure will be adopted in non-treatment-seeking individuals with AUD to establish the
safety and tolerability of probenecid as a novel pharmacotherapy.
This is a developmental/exploratory clinical trial that aims to test the hypothesis that proposes a potential
relationship between the pannexin 1 channel and alcohol. The goal of this proposal is to evaluate the safety and
tolerability of potential new therapeutic targets for the treatment of AUD.
The premise prompting this human laboratory study is based on the direct evidence from our preliminary work
with probenecid in a preclinical model of AUD. This work demonstrated that probenecid is able to reduce alcohol
consumption in alcohol-dependent rats. The scientific rationale for testing probenecid in AUD was derived by the
well-known mechanism of action of probenecid as a pannexin 1 channel inhibitor, its role in alcohol-induced
extracellular adenosine release, and that this process is promoted by a history of exposure to excessive alcohol.
In a controlled human alcohol laboratory setting, we will use behavioral and neuropsychopharmacological
approaches to establish the safety and tolerability of probenecid administered with alcohol (Aim 1). In our
secondary aims, we will test the hypotheses that treatment with probenecid will diminish alcohol's stimulant effect
(Aim 2) and alcohol tolerance (Aim 3).
In these aims, targeted pharmacological manipulation of probenecid with alcohol will be employed to evaluate
the safety and tolerability of probenecid when administered with alcohol. We included craving and subjective
preference measures as exploratory aims to inform a future larger trial. The proposed research is significant
because, using pharmacological probes, it will provide a much-needed insight into the fundamental
neurobiological mechanisms underlying alcohol biobehavioral effects with the goal of improving the therapeutic
outcomes for individuals with AUD.

## Key facts

- **NIH application ID:** 10141167
- **Project number:** 5R21AA027614-02
- **Recipient organization:** BROWN UNIVERSITY
- **Principal Investigator:** Carolina Luisa Haass-Koffler
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $192,969
- **Award type:** 5
- **Project period:** 2019-04-10 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10141167

## Citation

> US National Institutes of Health, RePORTER application 10141167, Probenecid as pharmacotherapy for alcohol use disorder (5R21AA027614-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10141167. Licensed CC0.

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