# Influence of Mavoglurant on Alcohol Craving and Drinking in Heavy Drinkers

> **NIH NIH P50** · YALE UNIVERSITY · 2021 · $351,128

## Abstract

Project 3: Influence of Mavoglurant on Alcohol Craving and Drinking in Heavy Drinkers
Suchitra Krishnan-Sarin, Ph.D.
Abstract
One of the main goals of the Center for Translational Neuroscience on Alcoholism (CTNA) is to
develop novel treatments for alcohol use disorders (AUDs). Understanding the neurochemical
mechanisms underlying drinking behaviors is key to the development of treatments for AUDs.
CTNA’s focus is on medications that target alcohol-related changes in the cortico-striatal
circuitry, specifically the glutamatergic pathways that promote drinking through altering the
balance between reward-related (model-based) and habitual (model-free) reinforcement. This
project, P3, links the mechanisms studied in P1 and P2 to targeted clinical examinations of
medications on alcohol drinking in heavy drinkers, and is a critical component of CTNA-5. We
propose to examine the influence of mavoglurant (MAV), a negative allosteric modular (NAM) of
the mGluR5 receptors, which may directly or indirectly (through NMDA receptors) normalize
alcohol-induced disturbances in cortico-striatal glutamate signaling. Existing preclinical and
clinical evidence suggest that mGluR5 receptors are upregulated by alcohol use, and preclinical
evidence also suggests that mGLuR5 NAM’s reduce alcohol drinking and reinstatement of
drinking after abstinence. We are fortunate to have access to MAV, a potent, selective, orally
bioavailable mGluR5 NAM developed by Novartis, which is safe and tolerable in multiple
neuropsychiatric populations. Our pilot evidence in social drinkers support the safety of MAV
(200 mg/day), even when combined with alcohol, and suggests that MAV reduces intoxication
from alcohol and brain responses to alcohol cues. P3 will examine the influence of MAV versus
placebo on lapse-relapse to alcohol drinking among heavy drinkers with AUD. P3 is inherently
innovative in both its conception and application because it identifies an important gap in clinical
knowledge – if targeting mGluR5 receptors influences alcohol craving and drinking - and then
brings to bear an experiment which combines a novel therapeutic agent (MAV) and two novel
behavioral science tools, the Cue-Exposure Paradigm (CEP) and the Alcohol Drinking Paradigm
(ADP) to investigate this question. P3 will address the primary questions of whether
mavoglurant alters alcohol drinking and craving, and other alcohol effects, in the CEP and the
ADP, and explore the associations of sex, family history of alcoholism and impulsivity to these
changes. The project is served by the clinical and translational cores of the CTNA but also
supports the goals of these cores to explore unique questions about how MAV changes model-
free/model-based behaviors, and the role of polygenic risk scores in the effects of MAV.

## Key facts

- **NIH application ID:** 10056547
- **Project number:** 2P50AA012870-21
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** SUCHITRA KRISHNAN-SARIN
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $351,128
- **Award type:** 2
- **Project period:** 2001-06-04 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10056547

## Citation

> US National Institutes of Health, RePORTER application 10056547, Influence of Mavoglurant on Alcohol Craving and Drinking in Heavy Drinkers (2P50AA012870-21). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10056547. Licensed CC0.

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