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.
Bone Fracture Healing 101
Basically, after a fracture you get an initial cartilaginous callus that forms across the gap. That callus then mineralizes, and is replaced by a bony callus, which is remodeled into mature bone. It is fairly well known that there are cannabinoid receptors that are involved in picking up the endocannibinoids (the cannabinoid molecules that your body produces) and have an effect in bone fracture healing.
- Cannabidiol/CBD is a key component in cannabis
- CBD is non-psychoactive, and the active compound in medical marijuana
- CBD reduces the negative effects of THC
- CBD is illegal, classified as a Schedule I drug in the United States and a Schedule II drug in Canada
What this Paper Did
They performed three experiments.
The first experiment was testing the effects of administering:
- just THC
- just CBD
- or a control
…on structural and mechanical properties of the fracture healing. These rats received femoral fractures following having a pin put in place to stabilize the fracture. They then began receiving 5 mg/kg/day doses of THC, CBD, or just the delivery solution. They then sacrificed the rats at various time points (2, 4, 6, and 8 weeks), and examined the fracture using microcomputed tomography and mechanical testing. At 4 weeks, it looks like this: figure, caption, where you can see callus formation. They found that the callus size in rats administered either THC or CBD was ~26% smaller than the control rats at the 4 week time point, but this was not present in the 6 or 8 week time points. This can be seen in this figure, caption. They then performed mechanical testing on the bone and found an enhancement of ~35% maximal force and ~50% work to failure in the CBD treated bones at the 8 week time point, but not in THC or control bones. The ultimate displacement at failure was not increased (how much the bone bends before it breaks), which indicates that the improvement in work to failure (basically, how tough the bone is) was due to strength improvements.
In the second experiment, they were testing the effect of delivery a mixture of equal amounts of THC and CBD on the mechanical properties of the callus because that is about the ratio recommended in most therapeutic cannabis. In this experiment, they only looked at the mechanical properties. The results can be seen here: figure, caption, but basically they found that the addition of THC slightly improved the maximal force, but eliminated the increased work to failure at 8 weeks. There were improvements at 6 weeks. I personally have problems with this comparison, because they were comparing the results from this 2nd experiment directly to the prior experiment, rather than adding additional groups to the 2nd experiment. It may be valid, but if there were odd changes they didn’t realize between experiments it could have an effect here.
Next, they wanted to assess the effects of THC and CBD on bone material properties so they could figure out what the mechanism of action of the CBD fracture healing effect. They analyzed the material density of the mineralized matrix, and found no differences between the treatment groups (see figure, caption), and found that there was no change in the actual mineralization. That means the effects of the CBD were coming from changes to the organic component of bone.
To show this, they cultured osteoblasts (the cells that produce bone), and administered CBD to the osteoblasts. They looked at the expression of PLOD1, which is an gene that creates an enzyme that plays a role in collagen crosslinking. The results are here: figure, caption. Basically, they found that there was an increase in expression for CBD at moderate levels, but decreased at higher concentrations (fairly expected). THC showed an increase at high levels of the PLOD2 gene, but didn’t show an effect on PLOD1.
They then performed spectroscopy on the callus tissue of the specimens from the first 2 experiments, and found the degree of collagen crosslinking was greater in samples that had been treated with CBD alone, but did not see any increase in either THC, or CBD+THC. I can’t post the figures with the data, because they appear to have forgotten to include them (I assume the publishers will catch this prior to full publication).
They found that delivery of CBD alone promoted improvement in some of the mechanical properties in fracture healing. The actual amount is a bit hard to tell, but it was enough to be statistically significant (P<0.05) using a very nonconservative test (Fisher’s LSD, which is commonly used, and in my opinion, overused). Their results also indicated that the impact comes during the late stages of bone healing (I would be curious to see a test with injections starting at 5 weeks or so), and they believe it may be due to increased collagen crosslinking. Further research is needed because this is very preliminary. There was no evidence that smoking cannabis (or vaping, or eating) would provide the benefits that they saw here, because they were testing using injections under the skin.
Cannabinoid, but not THC provides some improvement in mechanical properties during fracture healing, maybe due to increased collagen crosslinking. More research is necessary. This does not recommend smoking cannabis.
Maybe this could be used to stave off osteoporosis?