Systematic review of the literature on clinical and experimental trials on the antitumor effects of cannabinoids in gliomas

Abstract

To evaluate, through a systematic review of the literature, the antitumoral effects of cannabinoids on gliomas. Research included the following electronic databases: PUBMED, EMBASE, LILACS and The Cochrane Collaboration Controlled Trials Register. All published studies involving the antitumoral effects (cellular and molecular mechanisms) of cannabinoids were considered for this review. The bibliography search strategy included all publications of each of these databases until December 31, 2012. From 2,260 initially identified articles, 35 fulfilled the inclusion criteria for this review. All the studies included in this systematic review were experimental (in vivo and/or in vitro), except for one pilot clinical trial phase I/II involving humans. In all experimental studies included, cannabinoids exerted antitumoral activity in vitro and/or antitumoral evidence in vivo in several models of tumor cells and tumors. The antitumor activity included: antiproliferative effects (cell cycle arrest), decreased viability and cell death by toxicity, apoptosis, necrosis, autophagy, as well as antiangiogenic and antimigratory effects. Antitumoral evidence included: reduction in tumor size, antiangiogenic, and antimetastatic effects. Additionally, most of the studies described that the canabinnoids exercised selective antitumoral action in several distinct tumor models. Thereby, normal cells used as controls were not affected. The safety factor in the cannabinoids' administration has also been demonstrated in vivo. The various cannabinoids tested in multiple tumor models showed antitumoral effects both in vitro and in vivo. These findings indicate that cannabinoids are promising compounds for the treatment of gliomas.

Hypoxia-induced inhibition of the endocannabinoid system in glioblastoma cells

“…Notably, several studies have indicated that activation of CB2 plays a more dominant role in the inhibition of glioma and glioblastoma progression than CB1 (36,37). Although CB1 is predominantly expressed in the U-87 MG glioblastoma cells that we used in the present study, many glioma and glioblastoma cells express functional CB2 (38).…”

The Combination of Cannabidiol and Δ9-Tetrahydrocannabinol Enhances the Anticancer Effects of Radiation in an Orthotopic Murine Glioma Model

“…Both cannabinoids can reduce cell numbers by inhibiting cell-cycle progression and cell growth as well as by triggering apoptosis and engaging autophagy (19), and are also antiangiogenic and antimigratory (15). The two compounds have also been combined in a preparation that is currently licensed to treat multiple sclerosis, which is now undergoing trials in patients with glioma.…”

The Endocannabinoid System: A Target for Cancer Treatment

“…It has been reported that CB1 expression is unchanged, decreased, or even increased in GBM compared to control tissues [110]. In orthotopic and subcutaneous animal models of glioma, the treatment with cannabinoids resulted in a significant reduction of tumor growth [111]. Upon cannabinoid treatment, there was an increase in the activation of apoptotic cell death through the consequent activation of different pathways.…”