Cannabidiol in vivo blunts beta-amyloid induced neuroinflammation by suppressing IL-1beta and iNOS expression

Br J Pharmacol. 2007 Aug;151(8):1272-9. doi: 10.1038/sj.bjp.0707337. Epub 2007 Jun 25.


Background and purpose: Pharmacological inhibition of beta-amyloid (Abeta) induced reactive gliosis may represent a novel rationale to develop drugs able to blunt neuronal damage and slow the course of Alzheimer's disease (AD). Cannabidiol (CBD), the main non-psychotropic natural cannabinoid, exerts in vitro a combination of neuroprotective effects in different models of Abeta neurotoxicity. The present study, performed in a mouse model of AD-related neuroinflammation, was aimed at confirming in vivo the previously reported antiinflammatory properties of CBD.

Experimental approach: Mice were inoculated with human Abeta (1-42) peptide into the right dorsal hippocampus, and treated daily with vehicle or CBD (2.5 or 10 mg kg(-1), i.p.) for 7 days. mRNA for glial fibrillary acidic protein (GFAP) was assessed by in situ hybridization. Protein expression of GFAP, inducible nitric oxide synthase (iNOS) and IL-1beta was determined by immunofluorescence analysis. In addition, ELISA assay of IL-1beta level and the measurement of NO were performed in dissected and homogenized ipsilateral hippocampi, derived from vehicle and Abeta inoculated mice, in the absence or presence of CBD.

Key results: In contrast to vehicle, CBD dose-dependently and significantly inhibited GFAP mRNA and protein expression in Abeta injected animals. Moreover, under the same experimental conditions, CBD impaired iNOS and IL-1beta protein expression, and the related NO and IL-1beta release.

Conclusion and implications: The results of the present study confirm in vivo anti-inflammatory actions of CBD, emphasizing the importance of this compound as a novel promising pharmacological tool capable of attenuating Abeta evoked neuroinflammatory responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / toxicity*
  • Animals
  • Cannabidiol / administration & dosage
  • Cannabidiol / pharmacology*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Enzyme-Linked Immunosorbent Assay
  • Fluorescent Antibody Technique
  • Gene Expression Regulation
  • Glial Fibrillary Acidic Protein / metabolism
  • Hippocampus
  • Inflammation / chemically induced
  • Inflammation / drug therapy*
  • Interleukin-1beta / drug effects
  • Interleukin-1beta / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Neuroprotective Agents / administration & dosage
  • Neuroprotective Agents / pharmacology*
  • Neurotoxicity Syndromes / drug therapy*
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / drug effects
  • Nitric Oxide Synthase Type II / metabolism
  • Peptide Fragments / toxicity*
  • RNA, Messenger


  • Amyloid beta-Peptides
  • Glial Fibrillary Acidic Protein
  • Interleukin-1beta
  • Neuroprotective Agents
  • Peptide Fragments
  • RNA, Messenger
  • amyloid beta-protein (1-42)
  • Cannabidiol
  • Nitric Oxide
  • Nitric Oxide Synthase Type II