Measuring Neuroadaptations in Response to Very Low Nicotine Content Cigarettes

Not Applicable

Completed

Interventions: Drug: Normal nicotine content cigarettes
Drug: Very low nicotine content cigarettes

Brief Summary: The overall goal of this study is to determine if switching to very low nicotine content cigarettes changes the function of brain circuitry involved in incentive salience and executive control among dependent smokers.

Detailed Description: In a double-blind, randomized controlled trial, dependent smokers will be randomized to a 6-week very low nicotine content (VLNC) cigarette condition (N=50) or a 6-week normal nicotine content cigarette control condition (NNC; N=25). Participants will undergo functional magnetic resonance imaging (fMRI) scans at baseline and 6-weeks to investigate the nicotine-related modulation of brain circuitry involved in incentive salience valuation and executive control. Imaging tasks will engage the incentive salience of smoking cues and non-smoking rewards and executive control functions to identify changes in functional activity within, and effective connectivity between, known salience and executive control brain circuitry. A novel fMRI task using specialized odor presentation equipment and fMRI sequences will assess neural cue reactivity to smoke odors.

Recruitment & Eligibility

Inclusion Criteria

21-60 years old
Smoke >5 cigarettes per day
>1 year of daily smoking
No quit attempt in prior month and not planning to quit smoking within next 3 months
Able to understand and consent to study procedures
High school or lower educational attainment or annual household income < $50,000
Plan to live in local area next 3 months
Women not pregnant or nursing and taking steps to avoid pregnancy
Able to read and write in English
Access to computer with internet service that allows for Zoom

Exclusion Criteria

Use of non-cigarette tobacco products in the past 7 days
Use of illicit substances more than once a week in the past 3 months (excluding marijuana)
Current alcohol abuse impairing participation
MRI safety contraindications (e.g., metal implants, claustrophobia)
Unstable or significant medical conditions (e.g., chronic obstructive pulmonary disorder, coronary heart disease)
Major neurological conditions or brain trauma
Major surgeries planned in next 3 months
Use of smoking cessation medication in prior month (e.g., varenicline, patch)
Uncontrolled serious mental illness, suicidality, or inpatient psychiatric hospitalization in the past 6 months
Unwillingness to provide urine samples
Unwilling to smoke study assigned cigarettes for the remainder of the trial
Plans to move or take extended travel out of the area in the next 3 months
Any other condition or situation that would, in the investigator's opinion, make it unlikely that the participant could comply with the study protocol
Self-reported color blindness
Left-handedness
Smell dysfunction as determined via standardized assessment

Arm && Interventions

Group	Intervention	Description
Normal nicotine content cigarettes	Normal nicotine content cigarettes	Research cigarettes with normal nicotine content (0.8 mg/cigarette) similar to usual brand cigarettes.
Very low nicotine content cigarettes	Very low nicotine content cigarettes	Research cigarettes with very low nicotine content (0.03 mg/cigarette) compared to usual brand cigarettes.

Primary Outcome Measures

Name	Time	Method
Change in Blood Oxygen Level Dependent (BOLD) Signal Collected by Functional Magnetic Resonance Imaging (fMRI) During Monetary Delay Discounting Task	Change in BOLD signal from baseline to the 6-week visit.	Change from baseline to 6-weeks post-intervention in percentage of BOLD signal during hard vs. no choice conditions on a monetary delay discounting task in a left-sided cortical brain region encompassing the central opercular and dorsolateral prefrontal cortices.

Secondary Outcome Measures

Name	Time	Method
Change in Percentage of Immediate Choices on Monetary Delay Discounting Task	Changes from baseline to 6-weeks post intervention.	A difference score (6-weeks minus baseline) of the percentage of trials where the immediate (vs. delayed) monetary option was chosen out of all task trials during the monetary delay discounting task that was completed outside of the MRI scan.
Change in Self-reported Cigarettes Per Day	Average cigarettes per day during week 1 subtracted from average cigarettes per day during week 6.	Difference in week 6 mean minus week 1 mean of cigarettes used per day reported by participants on daily logs.