title: 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.
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06519, USA. sherry.mckee@yale.edu
authors.forename: Sherry A
authors.initials: SA
authors.lastname: McKee
authors.forename: Emily L R
authors.initials: EL
authors.lastname: Harrison
authors.forename: Stephanie S
authors.initials: SS
authors.lastname: O'Malley
authors.forename: Suchitra
authors.initials: S
authors.lastname: Krishnan-Sarin
authors.forename: Julia
authors.initials: J
authors.lastname: Shi
authors.forename: Jeanette M
authors.initials: JM
authors.lastname: Tetrault
authors.forename: Marina R
authors.initials: MR
authors.lastname: Picciotto
authors.forename: Ismene L
authors.initials: IL
authors.lastname: Petrakis
authors.forename: Naralys
authors.initials: N
authors.lastname: Estevez
authors.forename: Erika
authors.initials: E
authors.lastname: Balchunas
mesh_terms: D000328:Adult; D000437:Alcoholism / Q000150:complications / Q000188:drug therapy* / Q000523:psychology*; D001552:Benzazepines / Q000009:adverse effects / Q000627:therapeutic use*; D002492:Central Nervous System Depressants / Q000097:blood / Q000494:pharmacology; D004311:Double-Blind Method; D000431:Ethanol / Q000097:blood / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D018722:Nicotinic Agonists / Q000009:adverse effects / Q000627:therapeutic use*; D011810:Quinoxalines / Q000009:adverse effects / Q000627:therapeutic use*; D012907:Smoking / Q000188:drug therapy* / Q000523:psychology*; D000068580:Varenicline; D055815:Young Adult
chemical_list: D001552:Benzazepines; D002492:Central Nervous System Depressants; D018722:Nicotinic Agonists; D011810:Quinoxalines; D000431:Ethanol; D000068580:Varenicline