# Targeting Reinforcement Mechanisms for Smoking Cessation Using Very Low Nicotine Content Cigarettes in Individuals with Opioid Use Disorder and Chronic Pain

> **NIH NIH R34** · DUKE UNIVERSITY · 2024 · $241,500

## Abstract

Tobacco smoking, opioid use disorder, and chronic pain are highly comorbid conditions, and
smoking cessation in this population is extremely difficult to achieve. Co-administration of
nicotine and opioids results in mutual enhancement of positive reinforcement, which is likely to
contribute to persistent smoking in the context of opioid agonist therapy, such as office-based
buprenorphine treatment (OBBT). Moreover, nicotine has been shown to provide mild, short-
term anti-nociceptive effects, which may contribute to powerful negative reinforcement in
individuals with chronic pain. The goal of the proposed research is to examine whether
switching to very low nicotine content (VLNC) cigarettes can directly weaken these positive and
negative reinforcement cycles to improve cessation outcomes among people who smoke (PWS)
receiving OBBT with non-cancer chronic pain. The research will employ a randomized between-
subjects design to evaluate the effects of smoking VLNCs versus normal nicotine content (NNC)
cigarettes on smoking behavior, pain, craving and withdrawal symptoms, and motivation to quit
smoking. Ecological momentary assessment (EMA) will be used to examine changes in
bidirectional associations between pain, timing of buprenorphine dose, and smoking urge and
behavior as a function of cigarette condition. Participants will complete 1-week of baseline EMA
while smoking their usual brand of cigarettes; they will then be randomized to 4-weeks of NNCs
or VLNCs. EMA will continue during weeks 1 and 4 of study cigarette use. Participants will
attend weekly in-person visits to obtain biomarker verification of cigarette compliance and
complete self-report measures. At baseline and at the end of 4-weeks of study cigarette use, a
24-hr smoking abstinence test will be used to assess withdrawal symptoms, pain intensity and
sensitivity, and demand for usual brand cigarettes. At the conclusion of study cigarette use,
participants will engage in qualitative interviews about their experiences to guide treatment
development, and they will be provided with nicotine lozenges to support cessation. In general,
we hypothesize that switching to VLNCs will attenuate the bidirectional associations between
smoking, pain, and timing of buprenorphine administration as assessed via EMA, and will lead
to decreased symptoms of withdrawal and pain during the 24-hour abstinence test. We also
hypothesize that VLNCs will be associated with increased willingness to make a quit attempt,
and greater duration of achieved abstinence. These results will provide critical insights into the
role of nicotine in maintaining smoking/pain/opioid associations and the potential for VLNCs to
extinguish learned associations to promote smoking cessation in this vulnerable population.

## Key facts

- **NIH application ID:** 11057400
- **Project number:** 1R34DA060477-01A1
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Paolo Mannelli
- **Activity code:** R34 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $241,500
- **Award type:** 1
- **Project period:** 2024-09-15 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11057400

## Citation

> US National Institutes of Health, RePORTER application 11057400, Targeting Reinforcement Mechanisms for Smoking Cessation Using Very Low Nicotine Content Cigarettes in Individuals with Opioid Use Disorder and Chronic Pain (1R34DA060477-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11057400. Licensed CC0.

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