Biological effects of Cannabidiol on normal human healthy cell populations: Systematic review of the literature

A systematic review was performed to evaluate the biological effects of Cannabidiol (CBD), one of the major components of Cannabis Sativa, on normal human healthy cell populations in terms of cell viability, proliferation, migration, apoptosis and inflammation. Inclusion criteria were: studies on cell lines and primary cell culture from healthy donors, CBD exposure as variable, no CBD exposure as control and published in English language. Quality assessment was based on ToxR tool, with a score of reliability ranging from 15 to 18.Following the PRISMA statement, three independent reviewers performed both a manual and an electronic search using MEDLINE via PubMed, Scopus, Web of Science and Cochrane. From a total of 9437eligible articles, 29 studies have been selected. The average quality assessment score was 16.48.Theresults showed heterogeneous CBD concentration exposure (0.01-50 mu M or 0.1 nmol/mL-15 mg/mL). The definition of a threshold limit would allow the identification of specific effects on expected outcomes. From the data obtained CBD resulted to inhibit cell viability in a dose-dependent manner above 2 mu M, while in oral cell populations the inhibitory concentration is higher than 10 mu M. Moreover, it was observed a significantly inhibition of cell migration and proliferation. On the contrary, it was highlighted a stimulation of apoptosis only at high doses (from 10 mu M).Finally, CBD produced an anti-inflammatory effect, with a reduction of the pro-inflammatory cytokine gene expression and secretion. CBD down-regulated ROS production, although at high concentrations (16 mu M) increased ROS-related genes expression. The diffusion of CBD for therapeutic and recreational uses require a precise definition of its potential biological effects. A thorough knowledge of these aspects would allow a safe use of this substance without any possible side effects.