# Zonisamide for the Treatment of Alcohol Use Disorder in the Addiction Neuroclinical Assessment Framework

> **NIH NIH R01** · WASHINGTON STATE UNIVERSITY · 2020 · $665,501

## Abstract

PROJECT SUMMARY/ABSTRACT
Alcohol use disorder (AUD) is an alarming public health problem that costs the US more than $249 billion
annually. AUDs leads to a devastatingly diverse set of negative health outcomes, including significantly
increased risk of hypertension, stroke, pancreatitis, liver cirrhosis, Alzheimer’s disease, multiple cancers, and
multiple types of cognitive dysfunction. Disulfiram, naltrexone, and acamprosate are the only FDA-approved
medications for the treatment of AUD and are only modestly effective. Zonisamide (ZON) is an anticonvulsant
medication with GABAnergic, glutamatergic and monoaminergic effects which has shown significant promise
in animal and human laboratory settings, and small clinical trials for the treatment of AUD. ZON could represent
a critical new tool for clinicians, but previous studies have been limited by a couple of key factors (e.g., no
objective evidence recent alcohol consumption, no objective evidence of medication adherence) that this study
is designed to overcome. Theoretically framed within the Addiction Neuroclinical Assessment with
hypothesized mechanisms in core domains (i.e., incentive salience, negative emotionality and cognitive
function), and proceeding from a sound scientific premise we will target reduced alcohol use among AUD
patients in primary care using a carefully designed combination of contingency management (CM, or incentives
in exchange for objectively verified evidence of behavior) delivered at thrice-weekly visits during the first 4-
weeks of ZON treatment to jumpstart reductions in drinking. For the remaining 8-weeks of ZON, CM will be
delivered at weekly visits in exchange for evidence of 100% or higher medication adherence. The goal of this
study is to complete a double-blind, placebo-controlled RCT to evaluate the ability of ZON to significantly
decrease alcohol use among treatment-seeking AUD adults. Individuals will be randomized into 1 of 2 trial arms
that will receive: 1) ZON plus standard treatment (ST), which includes Take Control bibliotherapy modules and
CM through the 12-week treatment period (ZON+ST), or 2) Matched placebo plus ST (PLO+ST). The primary
outcome will be biochemically-verified alcohol use during the treatment period. We will use a 2-week, single-
blind placebo induction period wherein participants will be required to demonstrate a 75% medication
adherence rate before continuing into the 12-week treatment period. Follow-up will occur at 1, 6 and 12-months.
Our Specific Aims are to: 1) Determine if ZON+ST is more effective than PLO+ST for reducing biochemically-
verified alcohol use and other alcohol use outcomes; 2) Identify ANA-based mediators of treatment response
across the treatment groups; 3) Determine a.) if biological sex, baseline depression and baseline severity of
alcohol use interacts with treatment assignment to produce differential changes in our primary and secondary
outcomes; and b.) whether groups differ on adverse events or medication...

## Key facts

- **NIH application ID:** 10100732
- **Project number:** 1R01AA028796-01
- **Recipient organization:** WASHINGTON STATE UNIVERSITY
- **Principal Investigator:** Sterling M McPherson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $665,501
- **Award type:** 1
- **Project period:** 2020-09-15 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10100732

## Citation

> US National Institutes of Health, RePORTER application 10100732, Zonisamide for the Treatment of Alcohol Use Disorder in the Addiction Neuroclinical Assessment Framework (1R01AA028796-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10100732. Licensed CC0.

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