Opioids, Low Nicotine Cigarettes, and Chronic Pain

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

The purpose of this study is to evaluate the effects of switching to very low nicotine content (VLNC) cigarettes versus normal nicotine content (NNC) cigarettes on craving, withdrawal, and pain among individuals with chronic pain who smoke cigarettes daily and are attending office-based buprenorphine treatment (OBBT).

Study Overview

• Status: Recruiting
• Conditions: Chronic Pain; Tobacco Use; Opioid Substitution Treatment
• Intervention / Treatment: Behavioral: Very Low Nicotine Cigarettes (VLNC); Behavioral: Normal Nicotine Cigarettes (NNC)

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Clinical Research Coordinator; Phone Number: 919-907-9955; Email: ta141@duke.edu
• Study Contact Backup: Name: Clinical Research Coordinator; Phone Number: 984-327-6157; Email: lgf12@duke.edu

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Recruiting
      • North Pavilion
      • Contact: Clinical Research Coordinator; Phone Number: 919-907-9955; Email: sweitzerlab@duke.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Aged 21+ years who smoke cigarettes daily
• Chronic non-cancer musculoskeletal pain secondary to structural changes (e.g., low back pain, osteoarthritis)
• Have received stable office-based buprenorphine treatment for opioid use disorder for at least 30 days
• Self-report smoking at least 10 cigarettes/day
• Expired breath carbon monoxide (CO) level >8 ppm
• Have a smartphone capable of running software for ecological momentary assessment
• Open to exploring the possibility of quitting smoking

Exclusion Criteria:

• Pain specifically due to cancer
• Other significant health problems
• Major surgery within the past 6 months or planned surgery within the timeframe of the study
• Current disability litigation
• Use of electronic cigarettes or other non-cigarette tobacco products > 9 of the past 30 days
• Current use of nicotine replacement therapy or other cessation treatment
• Current daily or near-daily cannabis use
• History of psychotic disorder
• Acute suicidality or current unstable psychiatric disorder
• Positive pregnancy test
• Actively seeking smoking cessation treatment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Very Low Nicotine Cigarette (VLNC) Group; Participants in this condition will be provided with VLNCs and asked to switch to smoking only study cigarettes for 4 weeks.	Behavioral: Very Low Nicotine Cigarettes (VLNC); Spectrum NRC 102/103 (nonmenthol/ menthol) cigarettes, which have a nicotine content of approximately 0.4 mg/g tobacco.
Active Comparator: Normal Nicotine Cigarette (NNC) Group; Participants in this condition will be provided with NNCs and asked to switch to smoking only study cigarettes for 4 weeks.	Behavioral: Normal Nicotine Cigarettes (NNC); Spectrum NRC 600/601 (nonmenthol/ menthol) cigarettes, which have a nicotine content of approximately 15.8 mg/g tobacco.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nicotine Dependence as measured by the Fagerstrom Test of Cigarette Dependence (FTCD)	The FTCD has a total score of 0 to 10, where a greater score indicates a greater physical dependence on nicotine.	Baseline and weekly during study cigarette use (4 weeks)
Cigarettes per Day	Average cigarettes smoked per day during the past week will be calculated using timeline follow-back methods	Baseline and weekly during study cigarette use (4 weeks)
Pain as measured by the Brief Pain Inventory (BPI)	The BPI has an averaged score of 0 to 10, where a greater score indicates greater pain.	Baseline, during abstinence sessions, and at weekly visits during study cigarette use (4 weeks)
Mechanical Hyperalgesia	Mechanical hyperalgesia is a condition that causes increased sensitivity to mechanical stimuli after an injury to the skin. Discriminability and response bias will be assessed using a computerized pressure algometer.	Weekly visits 1 and 5 during study cigarette use (4 weeks), and during abstinence sessions
Smoking Withdrawal as measured by the Minnesota Withdrawal Scale (MNWS)	The MNWS has a total score range of 0 to 68, where a higher score indicates greater symptoms of withdrawal.	Baseline, during abstinence sessions, and at weekly visits during study cigarette use (4 weeks)
Cigarette Craving as measured by the Questionnaire of Smoking Urges-Brief (QSU-B)	The QSU-B has a total score range of 0 to 100, where a higher score indicates greater craving.	Baseline, during abstinence sessions, and at weekly visits during study cigarette use (4 weeks)
Cigarette Purchase Task - demand intensity	Outcomes for the cigarette purchase task will include demand intensity (i.e., consumption at $0) and Omax (i.e., max expenditure at any price point).	Weekly visits 1 and 5 during study cigarette use (4 weeks), and during abstinence sessions
Cigarette Purchase Task - Omax	Outcomes for the cigarette purchase task will include demand intensity (i.e., consumption at $0) and Omax (i.e., max expenditure at any price point).	Weekly visits 1 and 5 during study cigarette use (4 weeks), and during abstinence sessions
Pain-Smoking Associations as measured by Ecological Momentary Assessment (EMA)	EMA (also called experience sampling or daily diary method) involves repeated sampling of people's current experiences (e.g. pain) in real time in their natural environments.	Baseline, weeks 1 and 4 of study cigarette use
Buprenorphine-smoking associations as measured by Ecological Momentary Assessment (EMA) - smoking frequency	Within-person variability in smoking frequency assessed via EMA before and after buprenorphine administration.	Baseline, weeks 1 and 4 of study cigarette use
Buprenorphine-smoking associations as measured by Ecological Momentary Assessment (EMA) - craving	Within-person variability in smoking craving assessed via EMA before and after buprenorphine administration.	Baseline, weeks 1 and 4 of study cigarette use
Opioid Withdrawal as measured by the Short Opioid Withdrawal Scale (SOWS)	The SOWS consists of 16 symptoms rated in intensity by patients on a 5-point scale of intensity as follows: 0-not at all, 1-a little, 2-moderately, 3-quite a bit, 4-extremely. The total score ranges from 0 to 64, where a higher score indicates greater symptoms of withdrawal.	Baseline, during abstinence sessions, and at weekly visits during study cigarette use (4 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants willing to Quit Smoking	Decision (yes/no) to engage in the optional quit attempt	post-intervention, after 24 hrs abstinence
Smoking abstinence self-efficacy as measured by the Self-Efficacy Questionnaire (SEQ)	The SEQ has a total score range of 10 to 40, where a higher score indicates greater self-efficacy.	Weekly visits 1 and 5
Pain and Smoking Inventory (PSI)	The PSI total score is computed by averaging scores across the nine items. Items are endorsed on a seven-point Likert scale anchored at 0 (not true at all), 3 (somewhat true), and 6 (extremely true). Scores range from 0 to 6, where higher scores indicate greater perceptions that pain and smoking are interrelated.	Weekly visits 1 and 5
Barriers to Quitting Smoking in Substance Abuse Treatment (BSQ-SAT)	The BQS-SAT is an 11-item true-false instrument of perceived barriers to quitting smoking plus one open-ended item. The score can range from 0 to 4.86, where a higher score indicates a greater perceived barrier.	Weekly visits 1 and 5

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: National Institute on Drug Abuse (NIDA); National Institutes of Health (NIH)
• Investigators: Principal Investigator: Maggie Sweitzer, PhD, Duke University

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2025
• Primary Completion (Estimated): July 30, 2027
• Study Completion (Estimated): July 30, 2027

Study Registration Dates

• First Submitted: December 16, 2024
• First Submitted That Met QC Criteria: December 20, 2024
• First Posted (Actual): December 24, 2024

Study Record Updates

• Last Update Posted (Actual): January 9, 2026
• Last Update Submitted That Met QC Criteria: January 7, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Pathological Conditions, Signs and Symptoms; Behavior; Signs and Symptoms; Chronic Pain; Tobacco Use; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Neurotransmitter Agents; Cholinergic Agents; Ganglionic Stimulants; Nicotinic Agonists; Cholinergic Agonists; Nicotine
• Other Study ID Numbers: Pro00116478; 1R34DA060477-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The final dataset will include demographic, interview and self-report data. The investigators will share de-identified individual-participant level (IPD) data. Appropriate measures will be used for data de-identification and sharing, and informed consent will reflect those plans.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No