Examining the Effects of Cytisinicline on Neural Substrates of Cigarette Cue-reactivity

Inclusion Criteria:

1. be between the ages of 18 and 65 and provide informed consent;
2. smoke 5 or more combustible cigarettes per day;
3. not seeking treatment for smoking;

Exclusion Criteria:

1. current use of other smoking cessation aid (bupropion, varenicline, nortriptyline, NRT);
2. more than 3 months of smoking abstinence in past year;
3. use of non-cigarette tobacco product (pipe tobacco, cigars, smokeless tobacco, hookah) or electronic cigarettes more than 5 times in the 28-days prior to enrollment;
4. current use of psychoactive drug (excluding cannabis), as determined by urine toxicology;
5. current (past 12-month) DSM-5 diagnosis of substance use disorder for any substances other than tobacco and mild cannabis or mild-to-moderate alcohol use disorders;
6. lifetime history of psychotic disorders, bipolar disorders, or major depression with suicidal ideation;
7. current suicidal ideation or lifetime history of suicide attempt;
8. serious medical illness within past 3 months, including recent history of acute myocardial infarction, unstable angina, stroke, cerebrovascular incident, or hospitalization for congestive heart failure;
9. medical condition that may interfere with safe study participation;
10. renal impairment defined as a creatinine clearance (CrCl) greater than 60 mL/min (estimated with the Cockroft-Gault equation);
11. exceed Grade 2 laboratory abnormalities, based on FDA Guidance Document "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials";
12. uncontrolled hypertension (blood pressure ≥160/100 mmHg);
13. abnormal electrocardiogram;
14. non-removable ferromagnetic object in body;
15. claustrophobia;
16. serious head injury or period of unconsciousness (more than 30 minutes);
17. more than 250lbs;
18. Be pregnant, nursing, or planning to become pregnant while taking part in the study; and must agree to one of the following methods of birth control (if female), unless she or partner are surgically sterile:

    * Oral contraceptives
    * Contraceptive sponge
    * Patch
    * Double barrier
    * Intrauterine contraceptive device
    * Etonogestrel implant
    * Medroxyprogesterone acetate contraceptive injection
    * Hormonal vaginal contraceptive ring
    * Complete abstinence from sexual intercourse;
19. have experienced adverse effects to varenicline;
20. have an intense fear of needles or have had an adverse reaction to needle puncture.