title: Varenicline, naltrexone, and their combination for heavy-drinking smokers: preliminary neuroimaging findings.
abstract: BACKGROUND
  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.
authors.affiliation: Departments of Psychology .
authors.forename: Lara A
authors.initials: LA
authors.lastname: Ray
authors.forename: Kelly E
authors.initials: KE
authors.lastname: Courtney
authors.forename: Dara G
authors.initials: DG
authors.lastname: Ghahremani
authors.forename: Karen
authors.initials: K
authors.lastname: Miotto
authors.forename: Arthur
authors.initials: A
authors.lastname: Brody
authors.forename: Edythe D
authors.initials: ED
authors.lastname: London
mesh_terms: D000328:Adult; D000437:Alcoholism; D001552:Benzazepines / Q000008:administration & dosage; D001921:Brain / Q000473:pathology; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009271:Naltrexone / Q000008:administration & dosage; D009292:Narcotic Antagonists / Q000008:administration & dosage; D018722:Nicotinic Agonists / Q000008:administration & dosage; D011810:Quinoxalines / Q000008:administration & dosage; D012907:Smoking; D016540:Smoking Cessation; D016896:Treatment Outcome; D000068580:Varenicline
chemical_list: D001552:Benzazepines; D009292:Narcotic Antagonists; D018722:Nicotinic Agonists; D011810:Quinoxalines; D009271:Naltrexone; D000068580:Varenicline
keywords: Craving; fMRI; heavy drinker; naltrexone; smoker; varenicline