# A focus on alpha-1 blockade as a novel pharmacological treatment for alcohol use disorder

> **NIH NIH R01** · BROWN UNIVERSITY · 2021 · $80,992

## Abstract

It has been well established that stress plays an important role in the initiation and continuation of alcohol-
related behaviors. Studies indicate that individuals with alcohol use disorder (AUD) are at increased risk for the
dysregulation of stress, however, currently none of the FDA-approved medications for AUD target the stress
system. As such, novel pharmacological interventions targeting the noradrenergic system to regulate the stress
response in individuals with AUD provide a promising therapeutic opportunity. Further, it is well-described in
the literature that AUD is associated with chronic and prolonged immune inflammation. Therefore, pro/anti-
inflammatory cytokines may represent an important biological mechanism that contributes to the reinforcing
effect of alcohol and can be utilized as novel targets to develop AUD pharmacophore. The primary objectives
of this supplement are to examine the anti-inflammatory effect of doxazosin, an alpha 1 noradrenergic
receptor blocker, on serum levels of cytokines in individuals with AUD, and to assess the mediating role of
inflammatory cytokines as a mechanism by which doxazosin decreases alcohol consumption. Serum samples
will be collected from 184 treatment seeking individuals with AUD. Samples will be obtained at seven time
points over the 12-week study: at baseline, at the maximum tolerated dose (the laboratory phase and
naturalistic phase during week 5-11), and at the end of the study (week 12). Cytokine analysis using ELLA, an
automated enzyme-linked immunoassay system, will be tested as a secondary outcome (Aim 1) and mediator
of doxazosin on alcohol-related outcomes (Aim 2). This study will be the first to our knowledge to examine
cytokines as a mediator of doxazosin’s regulation of alcohol consumption. Additionally, to further
develop the “personalized” pharmacological intervention approach the exploratory aim of the supplement will
evaluate sex as a biological variable and racial group as moderators of doxazosin’s effect on alcohol
consumption. This Diversity Supplement will provide valuable insight further elucidating the mechanisms
underlying AUD and the mechanistic actions of novel pharmacological therapies for the treatment of AUD.

## Key facts

- **NIH application ID:** 10403910
- **Project number:** 3R01AA027760-03S1
- **Recipient organization:** BROWN UNIVERSITY
- **Principal Investigator:** Carolina Luisa Haass-Koffler
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $80,992
- **Award type:** 3
- **Project period:** 2019-09-10 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10403910

## Citation

> US National Institutes of Health, RePORTER application 10403910, A focus on alpha-1 blockade as a novel pharmacological treatment for alcohol use disorder (3R01AA027760-03S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10403910. Licensed CC0.

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