# Effects of ketamine on tobacco use disorder - Resubmission

> **NIH NIH R21** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2022 · $242,941

## Abstract

ABSTRACT
Arkansas ranks third in the nation for cigarette smoking prevalence (25% of the population) and ranks second
for smoking-attributed cancer mortality (33.5% mortality). More effective interventions for tobacco addiction are
needed, and there is an ongoing need for non-nicotine based interventions in particular. For example, nicotine
itself may potentially increase the risk of post-surgical complications. The reinforcing effects of nicotine may be
due to its effects on glutamatergic transmission, and the use of glutamatergic medications for tobacco
addiction has been proposed. A glutamate N-methyl-D-aspartate (NMDA) receptor antagonist, ketamine, has
shown preclinical efficacy in reducing nicotine self-administration, similar to other NMDA antagonists.
Furthermore, ketamine has shown promise in reducing craving, withdrawal symptoms, and use of other
addictive drugs in humans. However, ketamine’s effects on tobacco use disorder are not yet known and an
investigation of its impact on the neuropsychological substrates of tobacco addiction is warranted. While the
effects of ketamine on tobacco addiction have not been tested in humans, there is indirect evidence of its
potential efficacy to reduce tobacco use. To fill this gap in knowledge, we have begun collecting preliminary
data supporting the feasibility and tolerability of ketamine in smokers who complete lab measures of cigarette
craving and smoking latency before, and 24 hours after, an infusion of ketamine or placebo. To advance this
line of research, we propose a within-subject, cross-over trial of smokers who will receive an infusion of
ketamine and an active control drug in counter-balanced order, at least 2 weeks apart. In Aim 1, we will
measure changes in craving, tobacco withdrawal, and tobacco use behavior. In Aim 2, we will determine the
effects of ketamine on brain function using functional magnetic resonance imaging. The safety, tolerability, and
acceptability of ketamine will be assessed using physiological, drug effect, and side-effect measures. This
proposal is significant because it will be the first to translate preclinical research on a novel pharmacotherapy
for tobacco addiction. This information is valuable because knowing precisely how ketamine disrupts tobacco
addiction will help guide future therapeutic use of ketamine or the development of other pharmacotherapies
with similar mechanisms of action.

## Key facts

- **NIH application ID:** 10371688
- **Project number:** 1R21DA053393-01A1
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Merideth A. Addicott
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $242,941
- **Award type:** 1
- **Project period:** 2022-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10371688

## Citation

> US National Institutes of Health, RePORTER application 10371688, Effects of ketamine on tobacco use disorder - Resubmission (1R21DA053393-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10371688. Licensed CC0.

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