Could the Combination of Two Non-Psychotropic Cannabinoids Counteract Neuroinflammation? Effectiveness of Cannabidiol Associated with Cannabigerol

Medicina (Kaunas). 2019 Nov 18;55(11):747. doi: 10.3390/medicina55110747.


Background and Objectives: Neuroinflammation is associated with many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). In this study, we investigate the anti-inflammatory, anti-oxidant, and anti-apoptotic properties of two non-psychoactive phytocannabinoids, cannabigerol (CBG) and cannabidiol (CBD). Materials and Methods: The motoneuron-like cell line NSC-34 differentiated by serum deprivation and with the additional treatment of all-trans retinoic acid (RA) is a valid model to investigate molecular events linked to neurodegeneration in ALS. Results: Pre-treatment with CBG (at 2.5 and 5 µM doses) alone and in combination with CBD (at 2.5 and 5 µM doses) was able to reduce neuroinflammation induced by a culture medium of LPS-stimulated macrophages. In particular, the pre-treatment with CBD at a 5 µM dose decreased TNF-α levels and increased IL10 and IL-37 expression. CBG-CBD association at a 5 µM dose also reduced NF-kB nuclear factor activation with low degradation of the inhibitor of kappaB alpha (IkBα). CBG and CBD co-administered at a 5 µM dose decreased iNOS expression and increased Nrf2 levels. Furthermore, the pre-treatment with the association of two non-psychoactive cannabinoids downregulated Bax protein expression and upregulated Bcl-2 expression. Our data show the anti-inflammatory, anti-oxidant, and anti-apoptotic effects PPARγ-mediated. Conclusions: Our results provide preliminary support on the potential therapeutic application of a CBG-CBD combination for further preclinical studies.

Keywords: NSC-34 cells; amyotrophic lateral sclerosis (ALS); cannabidiol; cannabigerol; lipopolysaccharide (LPS); neuroinflammation.

MeSH terms

  • Cannabidiol / standards
  • Cannabidiol / therapeutic use
  • Cannabinoids / standards*
  • Cannabinoids / therapeutic use
  • Cell Culture Techniques / methods
  • Drug Therapy, Combination / methods
  • Drug Therapy, Combination / standards*
  • Drug Therapy, Combination / statistics & numerical data
  • Humans
  • Inflammation / prevention & control*
  • Neurons / drug effects*
  • Protective Factors


  • Cannabinoids
  • Cannabidiol
  • cannabigerol