Cannabidiol and Δ⁹-tetrahydrocannabinol alter human hematopoiesis by enhancing B cell lineage commitment

Cannabidiol (CBD) and Δ⁹-tetrahydrocannabinol (THC), the best characterized biologically active compounds in Cannabis sativa, are recognized for their therapeutic and immune modulating properties. An important knowledge gap is the effects of CBD and THC on different developing physiological systems. Here, the effects of CBD and THC on the early stages of human immune cell development from hematopoietic stem and progenitor cells (HSPCs) were investigated in vitro over 28 days. Concentrations used ranged from 1 to 10 μM. Both CBD and THC induced loss of CD34 expressing HSPCs in a concentration-dependent manner at several time-points, suggesting accelerated differentiation of HSPCs to downstream progenitors. Interestingly, both CBD and THC elicited a strong increase in CD19⁺ early B cell populations. With CBD and THC, there was also a trend towards an increase in the percentage of monocytes at early time points, with significant increases at several time points at 10 µM, and an increase in the proportion of megakaryocyte progenitors at later time-points. We also found that monocytes and type 2 classical dendritic cells that developed in presence of CBD had greater phagocytic capacity. Changes mediated by THC were not mediated through the cannabinoid type 2 receptor. This study demonstrated, for the first time, that CBD and THC alter human HSPC differentiation in a largely similar manner, and identified the differential effect each compound has on hematopoietic lineage development in vitro. These results support the need for more investigation to determine the safety of cannabis and cannabinoid product use from the perspective of immune cell development.