By Fabian Hernandez
Scientists in Israel continue to establish their work as the leading source of data on medical cannabis. In a combined study conducted primarily by researchers from Hebrew University of Jerusalem and Tel Aviv University, Cannabidiol (CBD) was found to enhance fracture healing and stimulate Lysyl Hydroxylase (a highly abundant enzyme involved in bone healing) activity in osteoblasts (bone building cells).
So, what does all that mean and how reliable is the evidence? Is it conclusive or inconclusive? From a biological perspective, the finding is rather significant because the research was conducted in a controlled environment under the supervision of 18 scientists from three different countries. Members of the Institute for Biomechanics from Zurich and Sweden’s Lund University Department of Biomedical Engineering and Department of Orthopedics collaborated with the Israeli team to map the biochemical interaction and effects of cannabis ligands (CBD and THC) on the skeletal system.
In the past, research that involved the effects of cannabis on the body’s biochemical structure didn’t involve such a large group of scientists. Within that group of scientists is the “Godfather” of cannabis research, Dr. Raphael Mechoulam, who discovered Tetrahydrocannabinol (THC) 50 years ago. Dr. Mechoulam’s work on CBD is considered the premier language on medical marijuana and the recent findings of its effect on bone fracture healing should put the world on alert because it’s the first time any data like this has ever been published.
How was the study performed?
The study consisted of three experiments. In the first experiment, THC or CBD were injected into rats with fractured femurs (approved by the Institutional Animal Care and Use Committee) to test its effects on the structural and mechanical properties of fracture healing. The second experiment analyzed the effects of a mixture of equal amounts of CBD and THC on a fracture callus (a connecting bridge remnant of a healed fracture). In both experiments, the molecular composition of the bone was monitored for eight weeks using Fourier Transform Infrared Spectroscopy (FTIR). The third experiment tested the effects of THC and CBD on the expression of osteoblast (cells that build bones) enzyme lysyl hydroxylase that catalyzes collagen crosslinking (bone healing).
How were the fractures analyzed?
Micro-computed tomography (3D X-ray imaging) was used for mechanical testing. The pins that stabilized the fracture were removed and the degree of bone mineralization (density of mineralized callus) was determined. Following the imaging process, work-to-failure (toughness) was tested by bending the bone 5mm/min until it fractured once again.
For the third experiment, newborn mouse osteoblasts (primary bone building cells) were cultured. They were grown for four days at 37 degrees Celsius. THC and CBD were added to the culture once it reached 80% maturation. RNA (created from DNA for protein synthesis) was extracted from the culture to test the abundance of lysyl hydroxylase levels. More specifically, the mRNA (holds the code for protein synthesis) expression of genes involved in lysyl hydroxylase production was analyzed.
What were the results?
Before the results are discussed, it needs to be understood that fractures heal through callus formation, creating cross bridges from osteoblast cell proliferation.
After 6-8 weeks, the first experiment revealed that callus size increased in rats that were administered CBD or THC and didn’t increase in rats that were given a controlled substance. This result concluded that stimulation of endocannabinoid receptors on bone cells with cannabis ligands improved the rate of bone healing. It was also determined in the first experiment that CBD significantly enhanced the mechanical properties and strength of the bone after eight weeks.
Since a high combination of THC and CBD is found in cannabis, the effects of THC and CBD administered together were tested on bone fractures. After eight weeks, THC was found to increase the maximal force and stiffness of the bone slightly more than CBD.
Finally, in the third experiment, CBD selectively increased mRNA levels of the lysyl hydroxylase (involved in fracture cross bridge formation) gene. This data is probably the most significant finding in cannabis research to date because it gave scientists insight into the genetic impact of cannabis on the body. Everything starts with genetics and this concrete data gives us a deeper insight into how cannabis influences the body’s physiology. The data proves that the marijuana research of the past hasn’t been in vain and we’ve only seen the tip of the iceberg.
The efforts of multiple scientists in the past have built a collection of data that inspires continual interest in the field of marijuana research. On a broader, physiological level, the effects of cannabis on multiple health conditions (epilepsy, pain, digestive motility) are undeniable. But the recent findings on bone fracture healing have given the medical world the biochemical proof that it’s been looking for. CBD stimulates bone-building cells to express the genes involved in producing the primary enzyme involved in bone healing, and this is an important step forward in the quest to learn more about the impact of cannabis on human health.