Combined varenicline and naltrexone attenuates alcohol cue-elicited activation in heavy drinking smokers. (1st August 2021)

• Record Type: Journal Article
• Authors: Grodin, Erica N.; Burnette, Elizabeth M.; Green, ReJoyce; Lim, Aaron C.; Miotto, Karen; Ray, Lara A.
• Is Part Of: Drug and alcohol dependence. Volume 225(2021)
• Publication Date: 2021-08-01
• Subjects: Varenicline -- Naltrexone -- fMRI -- Alcohol cue reactivity -- Heavy drinking smoker; Drug abuse -- Periodicals; Alcoholism -- Periodicals; 616.86
• DOI: 10.1016/j.drugalcdep.2021.108825
• Languages: English
• ISSNs: 0376-8716

Abstract

Highlights: Co-use of alcohol and cigarettes is common and is challenging to treat. Varenicline and naltrexone are used to treat nicotine and alcohol use disorder. The combination of varenicline and naltrexone may offer a better treatment outcome. The combination therapy attenuated neural alcohol cue reactivity. Naltrexone may be driving the reductions in cue-elicited brain response. Abstract: Background: There is a strong bidirectional relationship between the use of alcohol and cigarettes which results in various challenges for treating those who co-use both substances. While varenicline and naltrexone each have FDA-approval for nicotine and alcohol use disorder, respectively, there is evidence that their clinical benefit may extend across the two disorders. Critically, the effect of combined varenicline and naltrexone on neural reactivity to alcohol cues among heavy drinking smokers has not yet been studied. Probing the effect of the combination therapy on alcohol cue-reactivity may give insight to the mechanisms underlying its efficacy. Methods: Forty-seven heavy drinking smokers enrolled in two medication studies were randomized to receive varenicline alone (n = 11), varenicline plus naltrexone (n = 11), or placebo (n = 25). Participants completed an fMRI alcohol cue-reactivity task and rated their in-scanner alcohol craving. Whole-brain analyses examined the effect of medication on alcohol cue-elicited neural response. Results: Varenicline plus naltrexone attenuated alcohol cue-elicited activation in mesolimbic regions relative to varenicline alone and to placebo (Z > 2.3, p < 0.05). The combination varenicline and naltrexone group also endorsed lower in-scanner alcohol craving relative to varenicline alone group (p = 0.04). Conclusions: These findings provide evidence for the benefit of combined therapy of varenicline and naltrexone over varenicline alone for the attenuation of alcohol cue-elicited neural activation. This study provides a preliminary proof-of-mechanism for this combination pharmacotherapy and suggests that naltrexone may be driving the reductions in cue-elicited alcohol craving in the brain. Further clinical studies using the combined therapy to treat heavy drinking smokers are warranted.