Effects of cannabidiol on the differentiation of human monocytes into macrophages

Background: Innate immune myeloid cells, such as macrophages, contribute to chronic inflammation when consistently activated. Recently, cannabidiol (CBD), an active non-psychoactive constituent of the Cannabis sativa plant (i.e., Marijuana), has sparked interest as a safe and effective anti-inflammatory and immunomodulatory agent. This study aimed to investigate the CBD’s effects on the differentiation of human macrophages and their cell surface receptors. Methods: Peripheral blood was collected from healthy human donors. Monocytes, isolated from peripheral blood mononuclear cells, were differentiated with macrophage colony stimulating factor into monocyte-derived macrophages (MDM) with and without CBD (5 μM). Differentiated MDMs were then stained for different cell surface markers and analyzed by multicolor flow-cytometry. Proportions of anti-inflammatory (M2: CD206, CD71, CD163) and pro-inflammatory (M1: CD86, CD163) MDMs, and expression of myeloid lineage markers (CD14, CD16), chemokine receptor 5 (CCR5) and endocannabinoid type 2 receptor (CB2) were determined. Results: CBD promoted a shift towards a greater proportion of M2-type vs. M1-type MDMs (p<0.05, Fisher’s exact test). Cells displayed a significantly reduced expression of CD14, CD163, CD86, CCR5 and CB2 (p<0.05, Student t-test). Conclusions: CBD appears to promote differentiation of MDMs into anti-inflammatory phenotypes. Further studies are ongoing to determine the mechanistic pathways implicated in these processes, as these findings may have implications for the use of CBD in various disease conditions.