An endogenous cannabinoid (2-AG) is neuroprotective after brain injury

Nature. 2001 Oct 4;413(6855):527-31. doi: 10.1038/35097089.


Traumatic brain injury triggers the accumulation of harmful mediators that may lead to secondary damage. Protective mechanisms to attenuate damage are also set in motion. 2-Arachidonoyl glycerol (2-AG) is an endogenous cannabinoid, identified both in the periphery and in the brain, but its physiological roles have been only partially clarified. Here we show that, after injury to the mouse brain, 2-AG may have a neuroprotective role in which the cannabinoid system is involved. After closed head injury (CHI) in mice, the level of endogenous 2-AG was significantly elevated. We administered synthetic 2-AG to mice after CHI and found significant reduction of brain oedema, better clinical recovery, reduced infarct volume and reduced hippocampal cell death compared with controls. When 2-AG was administered together with additional inactive 2-acyl-glycerols that are normally present in the brain, functional recovery was significantly enhanced. The beneficial effect of 2-AG was dose-dependently attenuated by SR-141761A, an antagonist of the CB1 cannabinoid receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arachidonic Acids*
  • Body Temperature
  • Brain Edema / etiology
  • Brain Edema / prevention & control
  • Brain Infarction / prevention & control
  • Brain Injuries* / drug therapy
  • Brain Injuries* / metabolism
  • Brain Injuries* / pathology
  • Cannabinoids* / metabolism
  • Cell Death
  • Disease Models, Animal
  • Endocannabinoids
  • Gas Chromatography-Mass Spectrometry
  • Glycerides / administration & dosage
  • Glycerides / pharmacology
  • Glycerides / physiology*
  • Head Injuries, Closed / metabolism
  • Hippocampus / pathology
  • Male
  • Mice
  • Neuroprotective Agents / administration & dosage
  • Neuroprotective Agents / pharmacology*
  • Receptors, Cannabinoid
  • Receptors, Drug / metabolism


  • Arachidonic Acids
  • Cannabinoids
  • Endocannabinoids
  • Glycerides
  • Neuroprotective Agents
  • Receptors, Cannabinoid
  • Receptors, Drug
  • glyceryl 2-arachidonate