Safety and Molecular-Toxicological Implications of Cannabidiol-Rich Cannabis Extract and Methylsulfonylmethane Co-Administration

Abstract

Cannabidiol (CBD) is a biologically active, non-psychotropic component of Cannabis sativa whose popularity has grown exponentially in recent years. Besides a wealth of potential health benefits, ingestion of CBD poses risks for a number of side effects, of which hepatotoxicity and CBD/herb-drug interactions are of particular concern. Here, we investigated the interaction potential between the cannabidiol-rich cannabis extract (CRCE) and methylsulfonylmethane (MSM), a popular dietary supplement, in the mouse model. For this purpose, 8-week-old male C57BL6/J mice received MSM-containing water (80 mg/100 mL) ad libitum for 17 days. During the last three days of treatment, mice received three doses of CRCE administered in sesame oil via oral gavage (123 mg/kg/day). Administration of MSM alone did not result in any evidence of liver toxicity and did not induce expression of mouse cytochrome P450 (CYP) enzymes. Administration of CRCE did produce significant (p < 0.05) increases in Cyp1a2, Cyp2b10, Cyp2c29, Cyp3a4, Cyp3a11, Cyp2c65, and Cyp2c66 messenger RNA, however, this effect was not amplified by MSM/CRCE co-treatment. Similarly, no evidence of liver toxicity was observed in MSM/CRCE dosed mice. In conclusion, short-term MSM/CRCE co-administration did not demonstrate any evidence of hepatotoxicity in the mouse model.

Investigation of Drug-Interaction Potential for Arthritis Dietary Supplements: Chondroitin Sulfate, Glucosamine, and Methylsulfonylmethane

“…These results were supported by previous studies that found no inhibitory effects of CS and GCS on CYP2D6 and CYP2C9 [14,15]. Furthermore, through in vivo mice, intrahepatic gene expressions of CYPs were evaluated after the administration of MSM, and there were no significant inhibition or induction effects on CYPs [16].…”

Toxicological safety assessment of HempChoice® hemp oil extract; a proprietary extract consisting of a high concentration of cannabidiol (CBD) in addition to other phytocannabinoids and terpenes derived from Cannabis sativaL

“…Cannabinoids are extensively metabolized by CYP, and the highest level of expression of CYP is in the liver and intestine [ 47 ]. Kutanzi et al [ 48 ] studied the molecular changes induced by CBD-rich extracts (5.1% CBD and 0.2% THC) in male mice (C57BL6/J), concurrently given methylsulfonylmethane (MSM). In the mice receiving MSM in drinking water that were also administered daily doses of the CBD-rich extract, increases in hepatic mRNA for CYP1a2, CYP2b10, CYP2c29, CYP3a4, CYP3a11, CYP2c65, and CYP2c66 were observed and the concurrent administration of MSM was considered to have no effect on these parameters.…”