Authors:
Raphael Mechoulam, et col.
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.