The immunomodulatory properties of Cannabinoids- lessons from murine models of Bone Marrow Transplantation.

Introduction- In recent years, there has been a rapid increase in the medical use of cannabis. While cannabis is not registered as a drug or a medical product, the potential of cannabinoid-based medicines for the treatment of various conditions has led many countries around the world to authorize the use of such treatments. Cannabinoids, the biologically active constituents of Cannabis, have potent neuronal and immunological effects. However, the basic and medical research dedicated to medical cannabis and cannabinoids is limited. Hematopoietic stem cell transplantation (HSCT) is a well-established treatment for malignant and non-malignant hematological diseases. Allogeneic HSCT can cause the inflammatory condition, Graft versus Host Disease (GVHD), a major cause of morbidity and mortality in HSCT patients. In addition, slow, impaired or dysregulated reconstitution of donor derived immune cell populations cause susceptibility to both common and rare infections. The influence of cannabinoid-based treatments on hematologic reconstitution and on the development of GVHD after HSCT is largely unknown.

Material and methods- In our research, we compared the consequences of treatment with THC and CBD in vitro and in murine BMT models. Since it has been suggested that the combination of cannabinoids with other active molecules in the plant may achieve better clinical results than pure cannabinoids (known as the entourage effect), we also examined the differences between the effects of the pure cannabinoids and high THC/high CBD cannabis extracts.

Results and discussion- Our in vitro results demonstrate that the cannabinoid-based treatments decrease activated lymphocyte proliferation and affect cytokine secretion. We also discovered that CBD and THC utilize different receptors to mediate these effects. In vivo, in a syngeneic transplantation model, we demonstrate that all treatments inhibit lymphocyte reconstitution and show the inhibitory role of the cannabinoid receptor type 2 (CB2) on lymphocyte recovery. Although pure cannabinoids exhibited a superior effect in vitro, in an allogeneic (C57BL/6 to BALB/c) BMT mouse model, THC-high and CBD-high cannabis extracts treatment reduced the severity of GVHD and improved survival significantly better than the pure cannabinoids.

Conclusions- Cannabinoids have significant immunomodulatory properties, which should be considered in clinical use. Our results highlight the complexity of using cannabinoid-based drugs and the need for additional comparative scientific results.