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

Kristy R Kutanzi,Charles M Skinner,Igor Koturbash,Laura E Ewing,Stefanie Kennon-Mcgill,Mitchell R Mcgill,Bill J Gurley,Larry A Walker,Charles M Quick,Mahmoud A Elsohly

doi:10.3390/ijms21207808

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.

Highlights

Cannabidiol (CBD), a biologically active, non-psychotropic component of Cannabis sativa, has gained significant inroads into the US market over the last year with seemingly endless health claims positioning it as a proverbial panacea for treating stress and pain, boosting energy, enhancing circulation, and even curing arthritis and cancer [1,2,3]
This phytocannabinoid composition is comparable to those of cannabidiol-rich cannabis extract (CRCE) used in previous studies, as well as in products currently on the U
Other measurements were as follows: loss on drying—0.32%; heavy metals: lead, mercury, cadmium, and arsenic—not detected; aflatoxins: AFB1, AFB2, AGF1, and AFG2—not detected; Escherichia coli—absent; Salmonella—absent; Total Aerobic Microbial Count (TAMC)—

Summary

Introduction

Cannabidiol (CBD), a biologically active, non-psychotropic component of Cannabis sativa, has gained significant inroads into the US market over the last year with seemingly endless health claims positioning it as a proverbial panacea for treating stress and pain, boosting energy, enhancing circulation, and even curing arthritis and cancer [1,2,3]. Recent findings have shown that cannabidiol-rich cannabis extract (CRCE) given concomitantly with acetaminophen (APAP), one of the most common over-the-counter medications, exacerbates CBD hepatotoxicity, leading to sinusoidal obstruction syndrome-like liver injury and mortality in the mouse model [15]. These effects were associated with ingestion of high (therapeutic range) doses of CBD, the widespread and relatively indiscriminate distribution of CBD-containing products in the supplement market, and the potential inter-individual variability in response to CBD raises concerns as to co-ingestion of CBD and CBD-containing products with prescription and nonprescription drugs

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