Infusion of cannabidiol into infralimbic cortex facilitates fear extinction via CB1 receptors

Behav Brain Res. 2013 Aug 1;250:23-7. doi: 10.1016/j.bbr.2013.04.045. Epub 2013 May 1.


Previous studies have implicated cannabinoids in extinction of conditioned fear. We have recently showed that intraventricular infusion of the phytocannabinoid cannabidiol (CBD) facilitates fear extinction, but the brain regions underlying this effect remained unknown. Here we demonstrate that repeated microinjections of CBD into the infralimbic cortex (IL) facilitated fear extinction, as indicated by reduced levels of freezing during extinction test. Systemic administration of the CB1 receptor antagonist rimonabant blocked the effects of intra-IL CBD, suggesting that CBD acts through CB1 receptors to facilitate fear extinction. Our findings suggest a potential therapeutic use of CBD for extinction-based therapies of aversive memories in humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cannabidiol / pharmacology*
  • Cannabinoid Receptor Antagonists / pharmacology
  • Cerebral Cortex / drug effects*
  • Cerebral Cortex / physiology
  • Conditioning, Classical / drug effects*
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Electroshock / adverse effects
  • Extinction, Psychological / drug effects*
  • Fear / drug effects*
  • Fear / psychology
  • Freezing Reaction, Cataleptic / drug effects
  • Male
  • Microinjections
  • Piperidines / pharmacology
  • Pyrazoles / pharmacology
  • Rats
  • Rats, Long-Evans
  • Receptor, Cannabinoid, CB1 / metabolism*
  • Rimonabant
  • Time Factors


  • Cannabinoid Receptor Antagonists
  • Piperidines
  • Pyrazoles
  • Receptor, Cannabinoid, CB1
  • Cannabidiol
  • Rimonabant