Varenicline potentiates alcohol-induced negative subjective responses and offsets impaired eye movements

Abstract

Background: Varenicline (VAR) is a partial nicotinic receptor agonist that is an effective smoking cessation medication. Preliminary evidence indicates that it may also reduce alcohol consumption, but the underlying mechanism is not clear. For example, VAR may reduce alcohol consumption by attenuating its subjectively rewarding properties or by enhancing its aversive effects. In this study, we examined the effects of an acute dose of VAR upon subjective, physiological, and objective responses to low and moderate doses of alcohol in healthy social drinkers.

Methods: Healthy men and women (N = 15) participated in 6 randomized sessions; 3 sessions each with 2 mg VAR and placebo (PL) followed 3 hours later by a beverage containing PL, low-dose alcohol (0.4 g/kg), or high-dose alcohol (0.8 g/kg). Subjective mood and drug effects (i.e., stimulation, drug liking), physiological measures (heart rate, blood pressure), and eye tracking tasks were administered at various intervals before and after drug and alcohol administration.

Results: VAR acutely increased blood pressure, heart rate, ratings of dysphoria and nausea, and also improved eye tracking performance. After alcohol drinking (vs. PL), VAR increased dysphoria and tended to reduce alcohol liking ratings. It also attenuated alcohol-induced eye-tracking impairments. These effects were independent of the drug's effects on nausea before drinking.

Conclusions: Our data support the theory that VAR may reduce drinking by potentiating aversive effects of alcohol. VAR also offsets alcohol-induced eye movement impairment. The evidence suggests that VAR may decrease alcohol consumption by producing effects, which oppose the rewarding efficacy of alcohol.

Figure 1

Schematic showing the timing of drug and drink administration, and collection of subjective, cardiovascular, and behavioral measures during the experimental sessions. BL = Baseline, TP = Time point.

Figure 2

Effects of varenicline (2mg) upon subjective, cardiovascular and eye tracking measures before drinking. Asterisks indicate a significant difference between placebo and varenciline *p<0.05, **p<0.01, ***P<0.001.

Figure 3

Effects of varenicline (2mg) and alcohol upon negative mood. Bars represent the mean AUC ± SEM relative to pre-capsule baselines over the entire session.

Figure 4

Effects of varenicline and alcohol upon anti-saccade latency. Data points represent mean absolute scores ± SEM at repeated times during the sessions.