Chronic cannabidiol treatment improves social and object recognition in double transgenic APPswe/PS1∆E9 mice

Psychopharmacology (Berl). 2014 Aug;231(15):3009-17. doi: 10.1007/s00213-014-3478-5. Epub 2014 Mar 1.

Abstract

Rationale: Patients suffering from Alzheimer's disease (AD) exhibit a decline in cognitive abilities including an inability to recognise familiar faces. Hallmark pathological changes in AD include the aggregation of amyloid-β (Aβ), tau protein hyperphosphorylation as well as pronounced neurodegeneration, neuroinflammation, neurotoxicity and oxidative damage.

Objectives: The non-psychoactive phytocannabinoid cannabidiol (CBD) exerts neuroprotective, anti-oxidant and anti-inflammatory effects and promotes neurogenesis. CBD also reverses Aβ-induced spatial memory deficits in rodents.

Materials and methods: Thus we determined the therapeutic-like effects of chronic CBD treatment (20 mg/kg, daily intraperitoneal injections for 3 weeks) on the APPswe/PS1∆E9 (APPxPS1) transgenic mouse model for AD in a number of cognitive tests, including the social preference test, the novel object recognition task and the fear conditioning paradigm. We also analysed the impact of CBD on anxiety behaviours in the elevated plus maze.

Results: Vehicle-treated APPxPS1 mice demonstrated impairments in social recognition and novel object recognition compared to wild type-like mice. Chronic CBD treatment reversed these cognitive deficits in APPxPS1 mice without affecting anxiety-related behaviours.

Conclusions: This is the first study to investigate the effect of chronic CBD treatment on cognition in an AD transgenic mouse model. Our findings suggest that CBD may have therapeutic potential for specific cognitive impairments associated with AD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / physiopathology
  • Alzheimer Disease / psychology
  • Amyloid beta-Protein Precursor / genetics
  • Amyloid beta-Protein Precursor / metabolism
  • Animals
  • Anxiety / drug therapy
  • Anxiety / physiopathology
  • Cannabidiol / pharmacology*
  • Conditioning, Psychological / drug effects
  • Disease Models, Animal
  • Exploratory Behavior / drug effects
  • Fear / drug effects
  • Humans
  • Male
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neuropsychological Tests
  • Nootropic Agents / pharmacology*
  • Presenilin-1 / genetics
  • Presenilin-1 / metabolism
  • Recognition, Psychology / drug effects*
  • Social Perception*

Substances

  • APP protein, human
  • Amyloid beta-Protein Precursor
  • Nootropic Agents
  • PSEN1 protein, human
  • Presenilin-1
  • Cannabidiol