Nicotine Withdrawal and Reward Processing (NicWith)

Oklahoma State University, National Institutes of Health (NIH), National Institute on Drug Abuse (NIDA)

This study is designed to find out how smoking affects the way the brain responds to pleasure and how this impacts smokers' behavior. Participants will complete three sessions. The first session will be a screening and training visit to determine final eligibility. Eligible participants will work with a researcher to develop brief scripts about times when they smoke and do other activities. Next, participants will attend two magnetic resonance imaging (MRI) scans - one after abstaining from smoking for 24 hours and the other after smoking as usual. After the second MRI, participants will answer questions on their phone every day for two weeks.

Participants will abstain from smoking for 24 hours before one MRI scan and continue smoking as usual before the other

Participants will abstain from smoking for 24 hours before one MRI scan. Smoking abstinence will be confirmed using exhaled carbon monoxide breath testing

Participants will continue smoking as usual (i.e. "ad lib") before one MRI scan and smoke one additional cigarette immediately prior to scanning. Continued smoking will be confirmed using exhaled carbon monoxide breath testing.

Participants will continue smoking as usual (i.e. ad lib) in the day leading up to the scan and smoke one cigarette of their own brand immediately prior to scanning.

Anticipated and experienced pleasure based on self-report ratings acquired each day during the EMA phase

Inclusion Criteria: Generally healthy Age 21-55 Right-handed using a three-item scale Daily smoker of ≥ 6 cigarettes/day Smoking regularly for ≥ 1 year Have a smartphone capable of running the MetricWire application Able to read and understand English Able to identify at least 6 pleasurable activities they do not do concurrently with smoking or associate with smoking. Able to identify at least 6 unique locations/scenarios they do associate with smoking Exclusion Criteria: Planning to quit smoking within the next 60 days Currently seeking or receiving treatment for smoking cessation Use of smokeless tobacco, nicotine replacement products or electronic cigarettes more than 5 days in the past month. Breath alcohol level ≥.001. Participants may be allowed one reschedule at the discretion of the PI or other study staff. Positive toxicology screen for illicit drugs Marijuana will be tested for but will not be exclusionary Participants failing the toxicology screen may be allowed one re-screening attempt at the PI's discretion Participants with valid prescriptions who report using the medication as directed and meet all other eligibility criteria may be allowed to participate at the PI's discretion Current use of antipsychotic or stimulant medications. Significant health problems or those that would impact scientific goals of the project, including (but not limited to): Cancer, Bronchitis, Emphysema, COPD Asthma or Breathing Problems Insulin-Dependent Diabetes Heart disease, angina, heart failure, serious arrhythmia or heart attack within the past 6 months Systolic Blood Pressure > 160, Diastolic Blood Pressure > 100, HR > 115 bpm (one re-screen allowed). Glaucoma, color blindness or an uncorrected vision problem Significant hearing loss requiring the use of hearing aids or other hearing problems that would impact History of stroke, brain tumor, seizure disorder, or traumatic brain injury Metal implants (e.g. pacemaker, surgical pins, certain dental repairs), dental braces, or metal fragment injuries. Claustrophobia Weight > 350 pounds or unable to fit in the MRI scanner bore Current psychotic disorder, alcohol use disorder or drug use disorder for drugs other than cannabis (moderate or severe only, mild is allowable at PI's discretion). AUD and DUD in remission are also allowable at PI's discretion. Pregnant, breastfeeding or planning to become pregnant during the course of the study (females) Current enrollment in another smoking research study or having participated in a study involving daily use of Spectrum cigarettes or other reduced nicotine products within the past three months Irregular sleep-wake cycles (e.g. swing-shift work, unusual sleep pattern)

Detailed protocols, datasets and additional information will be available from the Principal Investigator and research team upon request. In order to maintain compliance with the Health Insurance Portability and Accountability Act (HIPAA) requirements, as well as university data security policies, all data will be anonymized according to HIPAA guidelines prior to being shared. Individual participant scripts will not be made publicly available due to privacy concerns and because this could impact the nature of information participants were willing to provide for scripts. Data will be provided in widely accessible formats for both self-report and imaging data. We will work with relevant administrative offices to obtain guidance regarding any required Data Use Agreements as needed.

We anticipate making data available within 6 months of study completion. It will be available for an indefinite period of time.