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.

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.

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

3 years, 4 months

Exclusion criteria was revised throughout the project (e.g., removed menthol use as exclusion) to accommodate challenges in recruitment.

Double-blind