Neuroprotective Effect of Cannabidiol, a Non-Psychoactive Component From Cannabis Sativa, on Beta-Amyloid-Induced Toxicity in PC12 Cells

J Neurochem. 2004 Apr;89(1):134-41. doi: 10.1111/j.1471-4159.2003.02327.x.

Abstract

Abstract Alzheimer's disease is widely held to be associated with oxidative stress due, in part, to the membrane action of beta-amyloid peptide aggregates. Here, we studied the effect of cannabidiol, a major non-psychoactive component of the marijuana plant (Cannabis sativa) on beta-amyloid peptide-induced toxicity in cultured rat pheocromocytoma PC12 cells. Following exposure of cells to beta-amyloid peptide (1 micro g/mL), a marked reduction in cell survival was observed. This effect was associated with increased reactive oxygen species (ROS) production and lipid peroxidation, as well as caspase 3 (a key enzyme in the apoptosis cell-signalling cascade) appearance, DNA fragmentation and increased intracellular calcium. Treatment of the cells with cannabidiol (10(-7)-10(-4)m) prior to beta-amyloid peptide exposure significantly elevated cell survival while it decreased ROS production, lipid peroxidation, caspase 3 levels, DNA fragmentation and intracellular calcium. Our results indicate that cannabidiol exerts a combination of neuroprotective, anti-oxidative and anti-apoptotic effects against beta-amyloid peptide toxicity, and that inhibition of caspase 3 appearance from its inactive precursor, pro-caspase 3, by cannabidiol is involved in the signalling pathway for this neuroprotection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / toxicity*
  • Animals
  • Apoptosis / drug effects
  • Calcium / metabolism
  • Cannabidiol / pharmacology*
  • Cannabis
  • Caspase 3
  • Caspases / metabolism
  • Cell Membrane / metabolism
  • Cell Survival / drug effects
  • DNA Fragmentation / drug effects
  • Dose-Response Relationship, Drug
  • Intracellular Fluid / metabolism
  • Lipid Peroxidation / drug effects
  • Neurons / drug effects*
  • Neurons / metabolism*
  • Neuroprotective Agents / pharmacology*
  • PC12 Cells
  • Peptide Fragments / toxicity*
  • Rats
  • Reactive Oxygen Species / metabolism

Substances

  • Amyloid beta-Peptides
  • Neuroprotective Agents
  • Peptide Fragments
  • Reactive Oxygen Species
  • amyloid beta-protein (1-42)
  • Cannabidiol
  • Casp3 protein, rat
  • Caspase 3
  • Caspases
  • Calcium