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Cannabinoids Reduce Inflammation but Inhibit Lymphocyte Recovery in Murine Models of Bone Marrow Transplantation

Laboratory of Immunotherapy and Bone Marrow Transplantation, Hadassah Medical Center, The Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 91120, Israel
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(3), 668; https://doi.org/10.3390/ijms20030668
Received: 19 December 2018 / Revised: 30 January 2019 / Accepted: 31 January 2019 / Published: 4 February 2019
(This article belongs to the Special Issue Trends in Molecular Research for Transplantation Immunology)
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. The influence of these treatments on hematologic reconstitution and on the development of graft versus host disease (GVHD) after bone marrow transplantation (BMT) is largely unknown. In this research, we compared the influence of D9 tetrahydrocannabinol (THC) and cannabidiol (CBD) on lymphocyte activation in vitro and in murine BMT models. Our in vitro results demonstrate that these 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. Our results highlights the complexity of using cannabinoids-based treatments and the need for additional comparative scientific results. View Full-Text
Keywords: hematopoiesis; bone marrow transplantation; graft versus host disease; lymphocyte; immune; cannabis; phytocannabinoids; D9 tetrahydrocannabinol; cannabidiol; cannabinoid receptor 2 hematopoiesis; bone marrow transplantation; graft versus host disease; lymphocyte; immune; cannabis; phytocannabinoids; D9 tetrahydrocannabinol; cannabidiol; cannabinoid receptor 2
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MDPI and ACS Style

Khuja, I.; Yekhtin, Z.; Or, R.; Almogi-Hazan, O. Cannabinoids Reduce Inflammation but Inhibit Lymphocyte Recovery in Murine Models of Bone Marrow Transplantation. Int. J. Mol. Sci. 2019, 20, 668.

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