# Targeting orexin to treat nicotine dependence

> **NIH NIH R03** · MCLEAN HOSPITAL · 2020 · $82,000

## Abstract

Abstract
Nicotine dependence is a prevalent and costly public health epidemic. While several treatment options exist,
the majority of individuals who try to quit will eventually relapse even when using currently available cessation
aids. Therefore, medications with novel mechanisms of action are needed to enhance cessation rates. For
instance, converging preclinical evidence shows that orexin antagonism has substantial promise for treating
addiction. This current R03 application will translate these preclinical findings into the clinical domain by
administering the FDA approved orexin antagonist, suvorexant, to nicotine dependent smokers. Given that
orexin antagonism blunts the motivation to attain abused substances in preclinical models, we hypothesize to
find a similar effect in smokers. Specifically, suvorexant will be administered in a dose dependent manner
using a double-blind, placebo controlled, cross over design. The impact of orexin antagonism on smoking cue-
induced craving and the subjective effects of acute smoking will be tested. Given that both orexin and nicotine
impact dopaminergic signaling, more general reward sensitivity also will be evaluated. Potential side effects
related to suvorexant’s action as a sleep aid also will be measured. This work will offer key information on the
role of orexin in nicotine dependence and will suggest whether orexin antagonists may be a viable treatment
strategy for nicotine dependence. This R03 application will provide pilot and feasibility data necessary for
larger projects that directly evaluate the neurobiological impact of orexin antagonism in nicotine dependent
individuals.

## Key facts

- **NIH application ID:** 9979831
- **Project number:** 5R03DA048941-02
- **Recipient organization:** MCLEAN HOSPITAL
- **Principal Investigator:** SCOTT E LUKAS
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $82,000
- **Award type:** 5
- **Project period:** 2019-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9979831

## Citation

> US National Institutes of Health, RePORTER application 9979831, Targeting orexin to treat nicotine dependence (5R03DA048941-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9979831. Licensed CC0.

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