High-dose baclofen attenuates insula activation during anticipatory anxiety in treatment-seeking alcohol dependant individuals: Preliminary findings from a pharmaco-fMRI study

Eur Neuropsychopharmacol. 2021 May:46:28-36. doi: 10.1016/j.euroneuro.2021.02.010. Epub 2021 Mar 15.


The GABA B agonist, baclofen, has been shown to reduce alcohol consumption in patients with alcohol use disorder and also those with comorbid anxiety. This study aimed to evaluate the effect of baclofen versus placebo on the BOLD response during an anticipatory anxiety fMRI task in treatment seeking alcohol patients. Participants included 28 alcohol dependant individuals who had received daily baclofen 30 mg (n = 10), 75 mg (n = 8) or placebo (n = 10) for at least 2 week on a randomized controlled trial (Morley, Leung et al. 2013, Morley, Baillie et al. 2018). Using functional magnetic resonance imaging (fMRI), we examined threat cue-elicited neural activation during a threat reactivity task 120 min following administration of BAC (30 mg or 75 mg) or placebo. Whole-brain analyses revealed no significant differences between the combined BAC doses versus PL. However, there were significant decreases in anticipatory threat cue-elicited activation observed in BAC 75 mg/day compared to PL participants in the insula. In response to threat cues, high dose (75 mg/day) baclofen administration attenuates activation in the insula and inferior frontal gyrus, relative to placebo. These preliminary findings suggests that modulating emotional regulation and attentional allocation during high threat stimuli may be mediated by GABA B receptors and may be a potential mechanism of action for baclofen's beneficial treatment effects for alcohol use disorder.

Keywords: Alcohol use disorder; Anxiety; Baclofen; Insula; Stress; Threat; fMRI.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol Drinking / drug therapy
  • Alcoholism* / diagnostic imaging
  • Alcoholism* / drug therapy
  • Anxiety / diagnostic imaging
  • Anxiety / drug therapy
  • Baclofen* / pharmacology
  • Baclofen* / therapeutic use
  • Ethanol
  • GABA-B Receptor Agonists / pharmacology
  • GABA-B Receptor Agonists / therapeutic use
  • Humans
  • Magnetic Resonance Imaging
  • Receptors, GABA-B


  • GABA-B Receptor Agonists
  • Receptors, GABA-B
  • Ethanol
  • Baclofen