Varenicline, low dose naltrexone, and their combination for heavy-drinking smokers: human laboratory findings

Abstract

Rationale: Heavy-drinking smokers constitute a sizeable and hard-to-treat subgroup of smokers, for whom tailored smoking cessation therapies are not yet available.

Objectives: The present study used a double-blind, randomized, 2 × 2 medication design, testing varenicline alone (VAR; 1 mg twice daily), low dose naltrexone alone (L-NTX; 25 mg once daily), varenicline plus naltrexone, and placebo for effects on cigarette craving and subjective response to alcohol and cigarettes in a sample (n = 130) of heavy-drinking daily smokers (≥10 cigarettes/day).

Methods: All participants were tested after a 9-day titration period designed to reach a steady state on the target medication. Testing was completed at 12 h of nicotine abstinence, after consuming a standard dose of alcohol (target breath alcohol concentration = 0.06 g/dl) and after smoking the first cigarette of the day.

Results: The combination of VAR + L-NTX was superior to placebo, and at times superior to monotherapy, in attenuating cigarette craving, cigarette and alcohol "high," and in reducing ad-lib consumption of both cigarettes and alcohol during the 9-day medication titration period.

Conclusions: These preliminary findings indicate that clinical studies of the combination of VAR + L-NTX for heavy drinkers trying to quit smoking are warranted and may ultimately improve clinical care for this sizeable and treatment-resistant subgroup of smokers.

Figure 1

Adjusted means and standard error of the mean for ratings post alcohol administration (controlling for baseline) for cigarette craving (a) and alcohol ‘high’(b). Significant group differences are indicated by *for p < .05 and ** for p < .01.

Figure 2

Adjusted means and standard error of the mean for post smoking ratings (controlling for post-alcohol ratings) of cigarette craving (a) and cigarette ‘high’ (b). Significant group differences are indicated by *for p < .05 and ** for p < .01.

Figure 2

Adjusted means and standard error of the mean for post smoking ratings (controlling for post-alcohol ratings) of cigarette craving (a) and cigarette ‘high’ (b). Significant group differences are indicated by *for p < .05 and ** for p < .01.

Figure 3

Adjusted means and standard error of the mean for drinks per drinking day (a) and cigarettes per day (b) during the 9-day titration period after controlling for pre-randomization ratings of drinks per drinking day and cigarettes per day, respectively. Significant group differences are indicated by *for p < .05 and ** for p < .01.