# Advancing Varenicline as a Treatment for Cannabis Use Disorder

> **NIH NIH UH3** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2021 · $981,666

## Abstract

ABSTRACT
Cannabis is the most commonly used illicit drug in the United States. Although cannabis use is widespread and
basic science research on cannabinoids is well-developed, advancements in medication development for
cannabis use disorder (CUD) have been limited. Varenicline, a selective nicotinic nACH receptor partial agonist
of the α4β2 subtype and a full agonist of the α7 subtype, is arguably the most effective pharmacotherapy for
promoting tobacco abstinence, and has also shown promise for the treatment of alcohol use disorder. Varenicline
may improve cannabis use outcomes through multiple mechanisms, including interaction with the mesolimbic
dopamine system, enhancement of cognitive functioning, and restoration of inhibitory control. To date, however,
varenicline has not been evaluated in individuals specifically seeking treatment for CUD. In this UG3/UH3
application, we propose to rapidly yet thoroughly assess the utility of varenicline for CUD to potentially advance
varenicline through the FDA's drug development approval pipeline. In the UG3 component, we will conduct a
six-week, placebo-controlled proof-of-concept clinical trial of varenicline for CUD, paired with pre- and post-
evaluations of cognitive functioning and neural circuitry involved in cannabis cue reactivity and inhibitory control
to elucidate the pharmacodynamics of varenicline as a treatment for CUD. If milestones of the UG3 component
are met, the UH3 project will be an adequately powered 12-week clinical trial with follow-up to fully assess the
efficacy of varenicline in this population.

## Key facts

- **NIH application ID:** 10202536
- **Project number:** 5UH3DA043231-05
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** Kevin M. Gray
- **Activity code:** UH3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $981,666
- **Award type:** 5
- **Project period:** 2016-09-15 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10202536

## Citation

> US National Institutes of Health, RePORTER application 10202536, Advancing Varenicline as a Treatment for Cannabis Use Disorder (5UH3DA043231-05). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10202536. Licensed CC0.

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