# Elucidating the Effects of Neuroimmune Modulation on Neural Substrates of Alcohol Cue and Stress Reactivity

> **NIH NIH F32** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $41,599

## Abstract

ABSTRACT
Alcohol use disorder (AUD) is a chronic relapsing disease with a major public health impact. The development
of efficacious medications to treat AUD is a crucial research priority. The identification of novel molecular
targets and the development of compounds for these targets represents a critical goal in medications
development. One promising treatment target is the modulation of neuroimmune function. Chronic alcohol
consumption induces a proinflammatory state, such that individuals with AUD have increased
neuroinflammation. Stress exposure also induces an inflammatory response in the brain and sensitizes
behavioral responses to alcohol. This proposal is based on recent indications that ibudilast (IBUD), a
neuroimmune modulator that targets neurotrophin signaling and neuroimmune function, represents a
potentially efficacious medication for the treatment of AUD. In rodents, IBUD reduced alcohol intake and
attenuated stress-induced relapse. In a human laboratory study, IBUD improved mood resilience during
alcohol cue and stress exposure and decreased tonic levels of alcohol craving. These results indicate the
IBUD is a promising alcohol addiction pharmacotherapy. However, the mechanisms of IBUD’s actions are not
fully understood. The objective of this NRSA application is to foster my development as a clinical neuroscientist
with a focus on medications development for AUD. This application proposes to add a novel neuroimaging
protocol to the Sponsor’s (Dr. Lara Ray) newly funded R01, a 12-week, double-blind, placebo-controlled
randomized clinical trial of ibudilast for AUD. The proposed study will investigate the effect of neuroimmune
modulation through IBUD on neural response to alcohol cues and psychosocial stress in treatment-seeking
individuals with AUD. Sixty-four treatment seeking participants with current AUD will complete 1 neuroimaging
visit as part of the Week 4 follow-up visit for the R01 trial. During this visit participants will complete two
neuroimaging paradigms evaluating neural responses to visual alcohol cues and psychosocial stress.
Participants will complete bi-weekly reports of their drinking during the 12-week trial. Specifically, Aim 1 tests
the hypothesis that IBUD will attenuate neural response to alcohol cues in reward circuitry compared to
placebo. Aim 2 tests the hypothesis that IBUD will reduce neural activation in the extended amygdala and
prefrontal cortex to psychosocial stress compared to placebo. The Exploratory Aim tests the hypothesis that in
IBUD-treated individuals, participants with lower neural ventral striatal activation to alcohol cues will have
better drinking outcomes. The present study represents an important step in: 1) identifying the neural
mechanisms underlying IBUD’s actions as an AUD treatment and 2) my scientific development and maturity as
an independent clinical and translational alcohol researcher with an interest in medications development.

## Key facts

- **NIH application ID:** 9982671
- **Project number:** 5F32AA027699-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Erica N Grodin
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $41,599
- **Award type:** 5
- **Project period:** 2019-07-01 → 2021-01-21

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9982671

## Citation

> US National Institutes of Health, RePORTER application 9982671, Elucidating the Effects of Neuroimmune Modulation on Neural Substrates of Alcohol Cue and Stress Reactivity (5F32AA027699-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9982671. Licensed CC0.

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