Varenicline effects on drinking, craving and neural reward processing among non-treatment-seeking alcohol-dependent individuals

Psychopharmacology (Berl). 2014 Sep;231(18):3799-807. doi: 10.1007/s00213-014-3518-1. Epub 2014 Mar 20.


Rationale: The α4β2 nicotinic acetylcholine receptor partial agonist varenicline has been reported to reduce drinking among both heavy-drinking smokers and primary alcoholics, and this effect may be related to varenicline-mediated reduction of alcohol craving. Among smokers, varenicline has been reported to modulate cigarette cue-elicited brain activation in several reward-related areas.

Objectives: This pilot study tested varenicline's effects on drinking, alcohol craving, and alcohol cue-elicited activation of reward-related brain areas among non-treatment-seeking alcohol-dependent individuals.

Methods: Thirty-five such individuals (mean age = 30, 57 % male, 76 % heavy drinking days in the past month, 15 smokers) were randomized to either varenicline (titrated to 2 mg) or placebo for 14 days, and were administered an alcohol cue reactivity fMRI task on day 14. A priori regions of interest (ROIs) were bilateral and medial orbitofrontal cortex (OFC), right ventral striatum (VS), and medial prefrontal cortex (mPFC).

Results: Despite good medication adherence, varenicline did not reduce heavy drinking days or other drinking parameters. It did, however, increase self-reported control over alcohol-related thoughts and reduced cue-elicited activation bilaterally in the OFC, but not in other brain areas.

Conclusions: These data indicate that varenicline reduces alcohol craving and some of the neural substrates of alcohol cue reactivity. However, varenicline effects on drinking mediated by cue-elicited brain activation and craving might be best observed among treatment-seekers motivated to reduce their alcohol consumption.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alcohol Drinking / drug therapy*
  • Alcohol Drinking / physiopathology
  • Alcohol Drinking / psychology
  • Alcoholism / drug therapy*
  • Alcoholism / physiopathology
  • Alcoholism / psychology
  • Benzazepines / pharmacology*
  • Benzazepines / therapeutic use
  • Brain / drug effects*
  • Brain / physiopathology
  • Brain Mapping
  • Craving / drug effects*
  • Cues
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Motivation
  • Nicotinic Agonists / pharmacology*
  • Nicotinic Agonists / therapeutic use
  • Pilot Projects
  • Quinoxalines / pharmacology*
  • Quinoxalines / therapeutic use
  • Reward*
  • Varenicline
  • Young Adult


  • Benzazepines
  • Nicotinic Agonists
  • Quinoxalines
  • Varenicline