Acute baclofen diminishes resting baseline blood flow to limbic structures: a perfusion fMRI study

Drug Alcohol Depend. 2012 Sep 1;125(1-2):60-6. doi: 10.1016/j.drugalcdep.2012.03.016. Epub 2012 Apr 17.


Background: Preclinical and clinical evidence show that the GABA B agonist, baclofen is a promising treatment for addictive disorders; however, until recently its mechanism of action in the human brain was unknown. In previous work we utilized a laboratory model that included a medication versus placebo regimen to examine baclofen's actions on brain circuitry. Perfusion fMRI [measure of cerebral blood flow (CBF)] data acquired 'at rest' before and on the last day of the 21-day medication regimen showed that baclofen diminished CBF bilaterally in the VS, insula and medial orbitofrontal cortex (mOFC). In the present study, we hypothesized that a single dose of baclofen would have effects similar to repeated dosing.

Methods: To test our hypothesis, in a crossover design, CBF data were acquired using pseudo continuous arterial spin labeled (pCASL) perfusion fMRI. Subjects were either un-medicated or were administered a 20mg dose of baclofen approximately 110 min prior to scanning.

Results: Acute baclofen diminished mOFC, amygdala, and ventral anterior insula CBF without causing sedation (family-wise error corrected at p=0.001).

Conclusions: Results demonstrate that similar to repeated dosing, an acute dose of baclofen blunts the 'limbic' substrate that is hyper-responsive to drugs and drug cues. Smokers often manage their craving and can remain abstinent for extended periods after quitting, however the risk of eventual relapse approaches 90%. Given that chronic medication may not be a practical solution to the long-term risk of relapse, acute baclofen may be useful on an 'as-needed' basis to block craving during 'at risk' situations.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Baclofen / pharmacology*
  • Cerebral Cortex / blood supply
  • Cerebral Cortex / drug effects
  • Cerebrovascular Circulation / drug effects*
  • Cluster Analysis
  • Cross-Over Studies
  • Data Interpretation, Statistical
  • Female
  • GABA Agonists / pharmacology*
  • Humans
  • Image Processing, Computer-Assisted
  • Limbic System / blood supply*
  • Limbic System / drug effects
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Perfusion
  • Reward
  • Smoking Cessation
  • Spin Labels
  • Young Adult


  • GABA Agonists
  • Spin Labels
  • Baclofen