# Effects of a Novel mGluR5 Negative Allosteric Modulator on Alcohol Drinking, Neurochemistry, and Brain Reactivity to Alcohol Cues in Alcohol Use Disorder

> **NIH NIH P50** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2021 · $196,026

## Abstract

SUMMARY
Alcohol use disorder (AUD) represents a significant public health concern and confers a large cost to society
due to violence, lost productivity, and healthcare expenditures. Despite decades of intense research efforts,
there are just a few FDA-approved medications for AUD, each of which are only modestly efficacious. GET73 is
a promising new medication that has shown promise in its initial development phase for improving AUD
symptoms, as evidenced by anti-alcohol-drinking and anxiolytic properties in preclinical/animal studies.
Preclinical research also indicates that GET73’s mechanism of action relates to its negative allosteric modulation
of the metabotropic glutamate subtype 5 receptor (mGluR5), a novel potential therapeutic target of growing
interest. Phase 1 clinical studies show GET73 to be safe and well-tolerated in both individuals with AUD and
healthy volunteers. Thus, considerable preliminary evidence supports GET73 as a new, safe, well-tolerated, and
potentially therapeutic treatment for AUD. Extending this preclinical and clinical research, the proposed research
project represents the first investigation of the effects of GET73 on alcohol drinking, both in a tightly controlled
laboratory setting and in the natural environment, in individuals with AUD. Neuroimaging indicators of purported
GET73 mechanisms of action, including fronto-cortical glutamate and GABA levels via proton magnetic
resonance spectroscopy (1H-MRS) and brain reactivity to alcohol cues via functional magnetic resonance
imaging (fMRI), will be investigated as potential mediators of the effect of GET73 on drinking. Non-treatment-
seeking participants with AUD (N=90) will be randomized to GET73 (300 mg, 3x/day) or placebo for the proposed
8-day study. Prior to randomization (Day-1), a pre-treatment MRI will be completed, during which anatomical,
1H-MRS, and alcohol-cue reactivity fMRI scans will be acquired. On Day-7, participants’ drinking over the
previous five days will be assessed, and all MRI procedures will be repeated. On Day-8, participants will consume
a standard priming drink and undergo a limited-access alcohol self-administration (bar-lab) paradigm, in a similar
fashion to previous Charleston ARC clinical studies. It is hypothesized that GET73-treated participants, relative
to placebo-treated participants, will drink less in the 5-day free-access period as well as during bar-lab limited-
access procedure. GET73-treated participants are also hypothesized to have increased fronto-cortical levels of
glutamate and GABA, reflecting normalization of the pathologically low glutamate and GABA levels typically
found in individuals with AUD who are not experiencing acute alcohol withdrawal, paired with decreased
reactivity to alcohol cues in key cognitive-control and cue-reactivity-related brain regions (e.g., medial prefrontal
cortex and ventral striatum, respectively). These effects are anticipated to mediate the relationship between
GET73 and alcohol drink...

## Key facts

- **NIH application ID:** 10055947
- **Project number:** 2P50AA010761-26
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** James Joseph Prisciandaro
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $196,026
- **Award type:** 2
- **Project period:** 1996-12-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10055947

## Citation

> US National Institutes of Health, RePORTER application 10055947, Effects of a Novel mGluR5 Negative Allosteric Modulator on Alcohol Drinking, Neurochemistry, and Brain Reactivity to Alcohol Cues in Alcohol Use Disorder (2P50AA010761-26). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10055947. Licensed CC0.

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