Varenicline, naltrexone, and their combination for heavy-drinking smokers: preliminary neuroimaging 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. Objective: The present study used a double-blind, randomized, 2 × 2 medication design, testing varenicline alone (VAR; 1 mg twice daily), naltrexone alone (NTX; 25 mg once daily), varenicline plus naltrexone, and placebo for effects on neural activation to cigarette cues in a sample (n = 40) of heavy drinking daily smokers (≥10 cigarettes/day). Methods: All participants were tested after a 10–12-day titration period designed to reach steady state on the target medication. Participants underwent functional neuroimaging (fMRI) for examination of brain responses to visual smoking-related (vs. neutral) cues. Results: Region of interest (ROI) analyses of brain responses to Cigarette vs. Neutral Cues indicated that the combination of VAR + NTX was associated with reduced activation of the bilateral anterior cingulate cortex as compared to placebo and to NTX alone. Exploratory whole-brain analyses also indicated significant differences in brain activation during cigarette cues in the active medications versus placebo condition. All medications suppressed left nucleus accumbens activation relative to placebo, suggesting the possibility that both medications, either alone or in combination, reduce neural signals associated with appetitive behavior. Conclusions: Although preliminary, these neuroimaging findings indicate that clinical studies of the combination of VAR + NTX for heavy drinkers trying to quit smoking may be warranted.

• Craving
• fMRI
• heavy drinker
• naltrexone
• smoker
• varenicline

Acknowledgements

This research was supported grants from the California Tobacco Related Disease Research Program (TRDRP 18KT-0020) and from the National Institute on Drug Abuse (DA030898) to LAR. Support for this study was also provided by a grant from the UCLA Clinical and Translational Science Institute (CTSI), grants UL1RR033176 and UL1TR000124. KEC was supported by the UCLA Training Program in Translational Neuroscience of Drug Abuse (T32 DA024635). LAR is a paid consultant for GSK.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this paper.