Cannabidiol, a Major Non-Psychotrophic Cannabis Constituent Enhances Fracture Healing and Stimulates Lysyl Hydroxylase Activity in Osteoblasts.
J Bone Miner Res. 2015 Mar 19. Epub 2015 Mar 19. PMID: 25801536
Natalya M Kogan
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 femora from rats given a mixture of CBD and THC for 8 weeks were markedly increased by CBD. This effect is not shared byΔ(9) -tetrahydrocannabinol (THC, the psychoactive component of cannabis), but THC potentiates the CBD stimulated work-to-failure at 6 weeks post fracture followed by attenuation of the CBD effect at 8 weeks. Using 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 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. This article is protected by copyright. All rights reserved.