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 D 9-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 (mCT), 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.

An anterior versus nonanterior LV lead position is independently associated with an increased likelihood of nonresponse to CRT and a higher risk of serious outcomes. Repositioning of an anteriorly placed LV lead to a nonanterior position should be considered in CRT nonresponders.

Motor cortical representation can be probed non-invasively using a transcranial magnetic stimulation (TMS) technique known as motor mapping. The mapping technique can influence features of the maps because of several controllable elements. Here we review the literature on six key motor mapping parameters, as well as their influence on outcome measures and discuss factors impacting their selection. 132 of 1,587 distinct records were examined in detail and synthesized to form the basis of our review. A summary of mapping parameters, their impact on outcome measures and feasibility considerations are reported to support the design and interpretation of TMS mapping studies.