Nicotine mediates smoking's addictive effects in the brain. The ratio of 3-hydroxycotinine to cotinine, known as the nicotine metabolite ratio, or NMR, is a genetically- informed biomarker reflecting hepatic CYP2A6 activity and the rate of nicotine metabolism. In light of a recent randomized controlled trial (RCT) in humans in Lancet Respiratory Medicine, which found that the NMR can be used to individualize treatment for smokers, our pilot study aims to determine the feasibility of using NMR to guide selection of pharmacotherapy in clinical populations of daily smokers.

Consenting participants will be assigned to guideline-based care (GBC: incorporating national guidelines and more recent evidence from clinical trials of pharmacotherapy for smoking cessation) or metabolism-informed care (MIC: identical to GBC but selection of medication based on NMR result). All participants received counseling from a nurse level certified tobacco counseling. After consent, participants undergo a blood draw for NMR, complete a baseline questionnaire, and are randomized to GBC or MIC. At approximately 1, 3, and 6 months post-consent, participants will provide follow up information via telephone questionnaire regarding symptoms, confidence in quitting, use of medications, and smoking status. At the 6-month follow-up time point, if a participant self-reports abstinence from smoking, the participant will be asked to complete a survey in-person and provide a sample of end-expired carbon monoxide for biochemical validation. At the 6 month time point, GBC participants who continue to smoke will be offered an additional phone call from the nurse tobacco counselor in which the results of the baseline NMR test will be given, along with a second prescription for a smoking cessation medication based on the NMR results (i.e., single arm crossover design). Two weeks after this additional phone call, the patient will be contacted for a final survey regarding use of medication and smoking status.

Inclusion Criteria:

• 18 years or older
• Smokes ≥ 5 cigarettes per day
• Willing to give up all forms of tobacco (5/10/2016 - 6/27/2016)
• Medically cleared (i.e., no contraindications in Section 3) to receive at least 2 FDA- approved smoking cessation medications
• Willing to use the medications for which medically cleared (individually, not in combination; only applicable if Medically Cleared = Yes)

Exclusion Criteria:

• Current diagnosis of schizophrenia, psychosis, active suicidal ideation, dementia, or severe mental retardation
• Receiving palliative or hospice care
• Currently pregnant or breastfeeding
• Hospitalized for a psychiatric condition in the past year (5/10/2016 - 6/27/2016)
• Hospitalized for a psychiatric condition in the past 3 months or change in psychiatric medications in last 3 months (6/28/2016 forward)
• Telephone problems that would preclude participation (e.g., can't receive calls reliably)
• Not able to read and speak English
• Abstinent from cigarettes for >3 days (b/c NMR not reliable after 72 hours)
• Used smoking cessation medications in the last 7 days (5/10/2016 - 6/27/2016)

Participant, Nurse, and RAs all blinded to random Arm assignment, none blinded to medication prescription