# PET Imaging of alpha-7-nAChR in Tobacco Use Disorder

> **NIH NIH R21** · JOHNS HOPKINS UNIVERSITY · 2020 · $245,625

## Abstract

SUMMARY
Although most smokers want to stop smoking, few successfully quit long-term. α7 nicotinic acetylcholine
receptors (nAChR) are an important pharmacological target for development of new smoking cessation
medications. α7 nAChRs regulate cognitive processes of attention, learning and memory, as well emotional
affect and reward, the same processes that are enhanced by acute nicotine, and disrupted during tobacco
withdrawal. Preclinical research provides evidence that α7 nAChR play a role in the reinforcing effects of
nicotine and expression of nicotine withdrawal, and that these receptors are upregulated in key brain regions
after chronic nicotine exposure. The proposed proof-of-concept pilot study will first quantify α7 nAChR in
recently abstinent tobacco smokers using human Positron Emission Tomography (PET) with an α7 nAChR
selective radiotracer (18F-ASEM) to determine if α7 nAChR availability is higher in smokers when compared to
healthy control nonsmokers, and if α7 nAChR availability is correlated with magnitude of tobacco use (Aim1).
Ain 2 will also explore the potential relationship of α7 nAChR availability to clinically relevant measures of
tobacco withdrawal during acute abstinence. Non-treatment seeking heavy smokers with TUD will be enrolled
into an outpatient protocol that includes 18F-ASEM PET imaging of α7 nAChR availability after 24-hrs of
smoking abstinence. Self-report of tobacco craving, withdrawal discomfort, and negative affect as well as heart
rate and performance on a task that measures attention processing will be assessed at baseline when smoking
as usual, on the first day of abstinence, then each study visit during the quit attempt. We will use a standard,
validated behavioral intervention (contingency management) to motivate smoking abstinence during the 8-day
quit attempt; at each study visit participants will receive incentive payments contingent upon criterion levels of
exhaled carbon oxide (CO) and urinary cotinine levels indicative of abstinence compliance, and number of
days of successful abstinence will be determined. Use of 18F-ASEM is approved by the FDA for human use
under an IND. These data provide a critical first step towards understanding α7 nAChR characteristics in TUD
and as a potential pharmacotherapeutic target to promote smoking cessation.

## Key facts

- **NIH application ID:** 9978034
- **Project number:** 5R21DA047795-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Elise M Weerts
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $245,625
- **Award type:** 5
- **Project period:** 2019-07-15 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9978034

## Citation

> US National Institutes of Health, RePORTER application 9978034, PET Imaging of alpha-7-nAChR in Tobacco Use Disorder (5R21DA047795-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9978034. Licensed CC0.

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