Varenicline reduces alcohol self-administration in heavy-drinking smokers

Abstract

Background: Alcohol and tobacco dependence are highly comorbid disorders, with preclinical evidence suggesting a role for nicotinic acetylcholine receptors (nAChRs) in alcohol consumption. Varenicline, a partial nicotinic agonist with high affinity for the alpha4beta2 nAChR receptor, reduced ethanol intake in rodents. We aimed to test whether varenicline would reduce alcohol consumption and alcohol craving in humans.

Methods: This double-blind, placebo-controlled investigation examined the effect of varenicline (2 mg/day vs. placebo) on alcohol self-administration using an established laboratory paradigm in non-alcohol-dependent heavy drinkers (n = 20) who were daily smokers. Following 7 days of medication pretreatment, participants were first administered a priming dose of alcohol (.3 g/kg) and subjective, and physiologic responses were assessed. A 2-hour alcohol self-administration period followed during which participants could choose to consume up to 8 additional drinks (each .15 g/kg).

Results: Varenicline (.5 +/- SE = .40) significantly reduced the number of drinks consumed compared to placebo (2.60 +/- SE = .93) and increased the likelihood of abstaining from any drinking during the self-administration period. Following the priming drink, varenicline attenuated alcohol craving and reduced subjective reinforcing alcohol effects (high, like, rush, feel good, intoxicated). Adverse events associated with varenicline were minimal and, when combined with alcohol, produced no significant effects on physiologic reactivity, mood, or nausea.

Conclusions: This preliminary investigation demonstrated that varenicline significantly reduced alcohol self-administration and was well tolerated, alone and in combination with alcohol in heavy-drinking smokers. Varenicline should be investigated as a potential treatment for alcohol use disorders.

Figure 1

Mean subjective measures of alcohol following consumption of the .3 g/kg priming dose by medication condition and time. (A) Alcohol craving (time × medication, F = 2.57, p < .05). (B) Subjective alcohol effects (mean of high, like, rush, feel-good, intoxicated) (medication, F = 4.53, p < .05]. VAS, visual analogue scale (1–100). Time points +10, 20, 30, and 40 are adjusted for baseline time point. *p < .05 for paired comparisons of varenicline versus placebo.

Figure 2

Mean physiologic reactivity following consumption of the .3 g/kg priming dose by medication condition and time. No significant effects of medication or of time by medication were demonstrated. (A) Systolic blood pressure (time, F = 6.64, p < .05). (B) Diastolic blood pressure (time, F = 3.47, p < .05). (C) Heart rate (time, F = 6.54, p < .05). (D) Skin temperature (time, F = 8.40, p < .05).

Figure 3

Scatterplot with line of best fit for alcohol craving during the priming drink (assessed as area under the curve [AUC]) by total drinks consumed during the 2-hour self-administration period.