The goal of this study is to assess varenicline vs. placebo for its effect on decreasing cue reactivity in light and intermittent smokers.

The study will consist of randomization to receive either varenicline or placebo over 6 weeks and include 5 study visits. Participants are offered an optional additional 6 weeks of active varenicline. Cue reactivity will be assessed in both a lab-based setting (viewing series of images and rating cravings) and in a real-world setting (text-based daily interaction).

Inclusion Criteria:

1. Age 18 years or above
2. Daily smoker using 10 or less cigarettes per day but a minimum of at least 1 cigarettes per week or 4 cigs/month.
3. Must be able to make it through a 24-hour period without nicotine withdrawal symptoms (specifically does not have new onset of irritability, headaches, insomnia, or intense cravings).
4. Willing to quit smoking in the next 30 days
5. Is able to provide written informed consent (in English) to participate in the study and is able to read/understand the procedures and study requirements.
6. Is willing to voluntarily sign and date an informed consent form that is approved by an institutional review board before the conduct of any study procedure.
7. If female and of childbearing potential, is willing to use medically acceptable contraceptive measures for the duration of the study. Acceptable methods of contraception include (1) surgical sterilization (such as tubal ligation or hysterectomy, (2) approved hormonal contraceptives (such as birth control pills, patches, implants or injections), (3) barrier methods (such as condom or diaphragm) used with a spermicide, or (4) an intrauterine device (IUD). Contraceptive measures such as rhythm method or Plan B™, sold for emergency use after unprotected sex, are not acceptable methods for routine use.
8. Have access to a cell phone that can send and receive SMS text messages.

Exclusion Criteria:

1. Use of a smoking cessation medication (e.g. nicotine replacement, varenicline, bupropion) in last 30 days.
2. Current use of tobacco product other than cigarettes (e.g. e-cigarettes, smokeless tobacco) in the last 30 days
3. Answer > 0 on suicidality question of Patient Health Questionnaire (PHQ-9) Depression Scale
4. Active alcohol use disorder or hazardous drinking. This will be screened with the AUDIT-C, and positive scores (4 or greater for men and 3 or greater for women)54,55 will result in study clinician assessment and discretion.
5. Use of illicit drugs in the last month (marijuana, cocaine, opiates, benzodiazepines, and/or methamphetamine)
6. Severe symptomatic depression and or anxiety (study medical provider discretion)
7. Diagnosis of bipolar disorder, schizophrenia, PTSD and or adult ADHD (study medical provider discretion)
8. Chronic medical illness including diabetes with the use of insulin, Hemoglobin A1c > 7 (study medical provider discretion), heart disease diagnosed by angiogram, or COPD diagnosed by pulmonary function testing and requiring an oxygen supply
9. Specific medications (Appendix 1)
10. Abnormal finding on physical exam (study medical provider discretion)
11. Positive Urine Pregnancy Test (women of child bearing potential only; QuickVue Urine Pregnancy)56
12. Positive Urine Toxicology-5 Screen (methamphetamine, cocaine, opiates, benzodiazepines, THC)
13. Unstable hypertension (Blood pressure > 160/100)
14. Renal failure with active or pending hemodialysis

No individual participant data will be shared.

Up to 12 weeks