Balanced Placebo Design With Varenicline: Pharmacological and Expectancy Effects on Medication Adherence

The current proposal will utilize the double-blind balanced placebo design to differentiate
expectancies versus pharmacologic mechanisms of varenicline administered to varenicline naïve
smokers seeking treatment (N = 80) for two-weeks. Race block randomization (controlling for
baseline expectancies) will be used to randomize participants. 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 (n = 20 for each): (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. Participants will be
told they received low dose (rather than placebo) due to concerns that participants will not
take a medication that they believe to be a 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 current proposal will test the following specific aims:

Specific Aim 1: Examine the main effects of instructional set and pharmacology. Hypothesis 1:
Main effects for TD instructional set and active medication administration will result in
reduced medication adherence compared with LD instructional set and placebo medication.

Specific Aim 2: Examine the interaction between instructional set and pharmacology.
Hypothesis 2: There will be a synergistic (i.e., non-additive) effect between instructional
set and pharmacology. Specifically, those assigned to the TD instructional set and active
medication group will result in a 50% discontinuation compared to a 20% discontinuation in
the TD instructional set and placebo medication group.

Exploratory Aim: Evaluate moderators of pharmacology and expectancy effects on medication
adherence. First, we will conduct exploratory examination of baseline medication expectancies
moderating the relationship between pharmacology and medication adherence. Second, we will
conduct an exploratory evaluation of potential moderators (e.g., gender and race) of
pharmacology and baseline medication expectancy.

Inclusion Criteria:

- 18 years or older

- Smoking at least 5 cigarettes per day (cpd) for the past year

- A carbon monoxide (CO) >10ppm

- English speaking

- Must own a cellphone with SMS text capacity with Internet access OR daily use of email

- Must be varenicline naïve

- Express a desire to quit smoking

Exclusion Criteria:

- Living in a restricted environment (e.g., prison or jail facility, etc.)

- Pregnant or nursing

- Currently enrolled in a smoking cessation treatment program, using NRT products, or
prescribed bupropion or varenicline

- Known allergy to varenicline

- History of kidney disease, dialysis or known kidney impairment

- Cognitive impairment or unstable psychiatric condition that interferes with the
informed consent process (individuals stable on psychiatric medications will be
included)

- Daily or exclusive use of other tobacco products

- Current suicidal or homicidal ideation or a suicidal attempt within the past 12 months

- History of stroke, heart attack, or seizures