The impact of three weeks of pre-quit varenicline on reinforcing value and craving for cigarettes in a laboratory choice procedure

Rationale: Varenicline, a partial nicotinic agonist, is theorized to attenuate pre-quit smoking reinforcement and post-quit withdrawal and craving. However, the mechanisms of action have not been fully characterized, as most studies employ only retrospective self-report measures, hypothetical indices of reinforcing value, and/or nontreatment-seeking samples. Objectives: The current research examined the impact of pre-quit varenicline (vs. placebo) on laboratory measures of smoking and food (vs. water) reinforcement and craving. Methods: Participants were 162 treatment-seeking smokers enrolled in a randomized controlled trial of smoking cessation (clinicaltrials.gov ID: NCT03262662). Participants completed two laboratory sessions: a pre-treatment session, ~ 1 week prior to beginning varenicline or placebo, and an active treatment session, after ~ 3 weeks of treatment. At each session, participants completed a laboratory choice procedure; on each of 36 trials, a lit cigarette, food item, or cup of water was randomly presented. Participants reported level of craving and spent $0.01–0.25 to have a corresponding 5–95% chance to sample the cue. Results: As predicted, spending was significantly higher on cigarette trials than water trials, and varenicline resulted in a greater between-session decline in spending on cigarette trials (but not water) than did placebo. Cigarette craving was enhanced in the presence of smoking cues compared to water, but neither average (tonic) cigarette craving nor cue-specific cigarette craving was significantly influenced by varenicline. Food spending and craving were generally unaffected by varenicline treatment. Conclusions: These laboratory data from treatment-seeking smokers provide the strongest evidence to date that varenicline selectively attenuates smoking reinforcement prior to quitting.