Cannabidiol, a Major Non‐Psychotropic Cannabis Constituent Enhances Fracture Healing and Stimulates Lysyl Hydroxylase Activity in Osteoblasts

Research output: Contribution to journalArticle

Abstract

Cannabinoid ligands regulate bone mass, but skeletal effects of cannabis (marijuana and hashish) have not been reported. Bone fractures are highly prevalent, involving prolonged immobilization and discomfort. Here we report that the major non-psychoactive cannabis constituent, cannabidiol (CBD), enhances the biomechanical properties of healing rat mid-femoral fractures. The maximal load and work-to-failure, but not the stiffness, of femurs from rats given a mixture of CBD and Δ9-tetrahydrocannabinol (THC) for 8 weeks were markedly increased by CBD. This effect is not shared by THC (the psychoactive component of cannabis), but THC potentiates the CBD stimulated work-to-failure at 6 weeks postfracture followed by attenuation of the CBD effect at 8 weeks. Using micro–computed tomography (μCT), the fracture callus size was transiently reduced by either CBD or THC 4 weeks after fracture but reached control level after 6 and 8 weeks. The callus material density was unaffected by CBD and/or THC. By contrast, CBD stimulated mRNA expression of Plod1 in primary osteoblast cultures, encoding an enzyme that catalyzes lysine hydroxylation, which is in turn involved in collagen crosslinking and stabilization. Using Fourier transform infrared (FTIR) spectroscopy we confirmed the increase in collagen crosslink ratio by CBD, which is likely to contribute to the improved biomechanical properties of the fracture callus. Taken together, these data show that CBD leads to improvement in fracture healing and demonstrate the critical mechanical role of collagen crosslinking enzymes. © 2015 American Society for Bone and Mineral Research.

Details

Authors
  • Natalya M Kogan
  • Eitan Melamed
  • Elad Wasserman
  • Bitya Raphael
  • Aviva Breuer
  • Kathryn S Stok
  • Rachel Sondergaard
  • Ana VVillarreal Escudero
  • Saja Baraghithy
  • Malka Attar‐Namdar
  • Silvina Friedlander‐Barenboim
  • Neashan Mathavan
  • Hanna Isaksson
  • Raphael Mechoulam
  • Ralph Müller
  • Alon Bajayo
  • Yankel Gabet
  • Itai Bab
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Orthopedics

Keywords

  • μCT, FTIR, FRACTURE HEALING, COLLAGEN CROSSLINKING, LYSYL HYDROXYLASE, CANNABIDIOL
Original languageEnglish
Pages (from-to)1905-1913
JournalJournal of Bone and Mineral Research
Volume30
Issue number10
Publication statusPublished - 2015
Publication categoryResearch
Peer-reviewedYes