Smoking continues to be the leading cause of preventable death in the U.S., accounting for one in
five deaths each year. Varenicline (Chantix) is a partial nicotinergic agonist and is the most
efficacious monotherapy for successful smoking cessation; however, long-term abstinence with
varenicline only ranges from 20% – 40%. One contributing factor to this low effectiveness may be
poor medication adherence due to nonspecific side effects (i.e., side effects not explained by the
pharmacology of the medication, but possibly due to negative medication expectancies or nicotine
withdrawal symptoms that are mistakenly attributed to medication use). Nonspecific side effects have
been linked to negative outcomes such as nonadherence, discontinuing effective treatment, and
attempts to treat these symptoms with additional medications. The current proposal will utilize the
double-blind balanced placebo design to differentiate expectancies versus pharmacologic
mechanisms of varenicline administered for two weeks to smokers seeking treatment. The double-
blind balanced placebo design includes a cross-balanced medication administration (active
medication v. placebo) and instructional set (told truth v. deception) resulting in four groups of
smokers seeking treatment: (1) told therapeutic dose (TD) medication + received TD medication; (2)
told TD medication + received placebo; (3) told low dose (LD) medication+ received TD dose
medication; (4) told LD medication + received placebo. Ecological momentary assessments (EMA) in
the form of Daily Dairies delivered via smartphone will assess real-time side effects, withdrawal
symptoms, cigarettes smoked, medication use, and reasons for medication non-adherence. The
specific aims for this proposal will examine the main effects and interaction of instructional set and
pharmacology on medication adherence (Aims 1 and 2) and evaluate moderators of pharmacology
and expectancy effects on medication adherence (Exploratory Aim). Assessing expectancies and
physiological barriers (i.e., non-specific side effects) to varenicline medication adherence will identify
targets to improve medication adherence and to develop behavioral interventions that can modify and
reframe negative expectancies and experiences. The specific aims of this project will be completed in
conjunction with a formal training plan, sponsored by Dr. Karen Cropsey, Dr. Peter Hendricks, Dr.
Michael Businelle, Dr. Richard Shelton, and Dr. Sylvie Mrug. This training plan includes: 1)
pharmacological research development, 2) EMA methodology, 3) advanced longitudinal data
analysis, and 4) research dissemination and mentorship.