Combining Varenicline and Naltrexone for Smoking Cessation

This study is a double-blind, randomized clinical trial using a two group medication design consisting of the combination of VAR (1 mg twice daily) + NTX (50 mg once daily) and VAR (1 mg twice daily) + PLA (matched to NTX), for smoking cessation in a sample of heavy drinking daily smokers who want to quit smoking and reduce drinking. All participants will be daily smokers (≥ 5 cig/day) who are also heavy drinkers according to the National Institute on Alcohol Abuse and Alcoholism (NIAAA) guidelines: for men, > 14 drinks per week or ≥ 5 drinks per occasion at least once per month over the past 12 months; for women, > 7 drinks per week or ≥ 4 drinks per occasion at least once per month over the past 12 months. A total of 274 participants will be randomized, 137 to each medication group.

Inclusion criteria

• Be treatment-seeking for smoking cessation and have a desire to reduce or quit drinking
• Be between the ages of 21 and 65
• Be able to provide informed consent
• Smoke 5 or more cigarettes per day for the past year
• Currently drink heavily according to the National Institute on Alcohol Abuse and Alcoholism (NIAAA) guidelines: for men, > 14 drinks per week or ≥ 5 drinks per occasion at least once per month over the past 12 months; for women, > 7 drinks per week or ≥ 4 drinks per occasion at least once per month over the past 12 months
• Pass the physical exam and associated laboratory tests, as determined by study physician

Exclusion criteria

• Have clinically significant alcohol withdrawal, indicated by a score ≥ 10 on the Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) and assessed at the in-person screening visits
• Have lifetime DSM-V diagnosis of schizophrenia, bipolar disorder, a psychotic disorder, or any other psychiatric disorder as determined by the clinical interview
• Have major depressive disorder within the past year requiring treatment as determined by the clinical interview using DSM-V criteria
• Have a current or lifetime DSM-V diagnosis of a substance use disorder, other than for alcohol or nicotine, as determined by the clinical interview
• Have a prior history of taking FDA approved medications (i.e. varenicline or bupropion) for smoking cessation
• Be currently using any forms of nicotine replacement therapy (past use is acceptable)
• Be currently using tobacco products other than cigarettes (such as e-cigarettes, cigars, or chewing tobacco)
• Have a serious medical illness (significant cardiovascular disease; uncontrolled hypertension; hepatic or renal disease) that would contraindicate participation, as determined by the study physician
• Be currently taking insulin or oral hypoglycemic medication
• Be currently taking opioid pain medications or any form of opioid agonist maintenance therapy (such as methadone or buprenorphine)
• Be currently taking any other psychoactive medications; such as anti-depressants, mood stabilizers, anti-seizure medications, sedatives-hypnotics, anxiolytics, stimulants or antipsychotics
• Have self-reported use of cocaine, methamphetamine, heroin or other illicit drugs in the previous 60 days, verified by urine toxicology screen
• For women, must not be pregnant (as indicated by self-report or a positive pregnancy test at any study visit), nursing, or planning to become pregnant while taking part in the study, and must agree to a reliable method of birth control