Cannabidiol-enriched Cannabis sativa L. extract modulates inflammatory-induced human peripheral mononuclear cells response

Recent studies propose non-psychotropic Cannabis sativa L. as a candidate drug having a role in the pathogenic mechanisms involved in inflammation [1]. In order to evaluate the biological effect of a chemically standardized extract of C. sativa var. carmagnola dried female inflorescences (CSE) and its main constituents, the purpose of this study was to investigate the modulation of cannabinoid receptors (CBr) and pro-inflammatory cytokines in an acute inflammatory stress in vitro model. CSE was chemically characterized by HPLC-DAD and GC. The CSE biological effect was investigated on human peripheral blood mononuclear cells (PBMC) firstly exposed to the endotoxin LPS (2, 6, 24 hours) in order to evaluate CBr and cytokines regulation. Then, cells were pre-treated with CSE and its main components at the concentration of 1 μg/ml, followed by a 2 hours stimulation with the endotoxin LPS. CSE was found to contain cannabidiol (CBD) >20%, THC <0.6% and β-caryophyllene as principal sesquiterpene; flavonoids were found only <0.1%. Short term exposure to LPS significantly downregulated CB1r and CB2r gene expression and induced IL-1β, IL-6 and TNF-α release. CBr transcription resulted attenuat by pre-treatment with CSE, and more with CBD. Moreover, the LPS-induced release of the pro-inflammatory cytokine IL-6 was attenuated by CSE and CBD treatment. C. sativa extract and its main constituent CBD were able to regulate the LPS-induced inflammatory PBMC response through the modulation of CBr expression. These results contribute to support the role of the non-psychotropic cannabis compounds in the management of the inflammatory mechanisms.