Current status and prospects for the application of cannabinoids in organ transplantation

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Brian Earl

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Abstract





Graft versus host disease and allograft rejection are frequent complications of allogeneic hematopoietic stem cell transplantation and solid organ transplantation, respectively. The probability of developing either condition is dependent upon the magnitude of genetic disparity between donor and recipient. In both contexts, alloimmune-mediated processes are responsible for disease pathogenesis and the subsequent complications that are associated with significant morbidity and mortality. Existing prophylactic regimens consisting of intensive immunosuppression are limited by high incidences of graft failure, infection, and toxicity. Cannabinoids are a diverse family of natural and synthetic molecules that, through interaction with the endocannabinoid system, have potent immunoregulatory properties. However, the applicability of cannabinoids to the prevention of graft-versus-host disease and allograft rejection has not been established. This article offers insight into our current understanding of the immunopathophysiology of graft-versus-host disease and allograft rejection, relevant cannabinoid- mediated immune modulation, and emerging evidence on the role of cannabinoids in transplant immunology. With the need for more effective prophylactic strategies and the concordant interest in cannabinoid-based therapeutics, it is pertinent to determine whether the endocannabinoid system can be therapeutically targeted in the post-transplant setting.