Cannabinoid profile and regulatory compliance of non-scheduled cannabinoid-containing products in South Africa

Abstract

Cannabis contains numerous chemical compounds and has a multitude of therapeutic and pharmacological properties. The most-studied compounds in the cannabis plant are the cannabinoids, of which Δ⁹-tetrahydrocannabinol (Δ⁹-THC) and cannabidiol (CBD) are the most well-known. South African cannabis legislation has seen momentous changes in recent years, and recreational and medicinal cannabis use was legalised in 2018. There are a variety of cannabis products available for purchase in South Africa, many in the form of CBD oils. The aim of this study was to determine the cannabinoid profile in cannabinoid-containing products and to determine the compliance of these products to South African regulations. Six CBD oils available in South Africa were selected for analysis and purchased online in both a ‘summer’ and ‘winter’ batch. A robust, validated liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed for the analysis of four cannabinoid compounds; THC, CBD, cannabinol (CBN) and tetrahydrocannabinolic acid-A (THCA). Cannabinoid content and batch-to-batch conformity was assessed in two batches of the six CBD oils. Targeted analysis was achieved with a C18 Phenomenex Gemini column (2 x 100 mm) using an isocratic gradient programme consisting of 10 mM ammonium formate in water: acetonitrile (0.1% formic acid) 32.5:67.5 at a flow rate of 0.4 mL/min for 13 minutes. Additionally, the immediate and outer container labels of all CBD oils were scrutinized to determine compliance to labelling regulations. The optimised method was validated according to the International Conference on Harmonisation (ICH) guidelines, and the limit of detection (LOD) was determined using the calibration curve for each analyte. Regarding CBD concentration, the selected CBD oils failed to meet label claims as advertised CBD content was mislabelled in almost all CBD oils. Three CBD oils contained CBD concentrations between one quarter and one half higher than the advertised amount, while two contained double, and two contained triple the advertised CBD content. Conversely, the measured CBD concentrations in two CBD oils were between a quarter and a half less than the advertised CBD content. The disparity between advertised and measured CBD content may be ascribed to the differences in cannabinoid extraction and detection methods employed, as well as the type of cannabis strain used. Concentrations of THC, CBN and THCA were not detected in significant amounts in five of the six CBD oils (<0 mg/mL, with detection limits of 293.2 ng/mL for THC, 30.9 ng/mL for THCA and 47.2 ng/mL for CBN). High concentrations of both THC and CBN were detected in one CBD oil; at 47.97 mg THC and 15.4 mg CBN in batch 1, and 131.5 mg THC and 26.3 mg CBN in batch 2, respectively. A lack of batch-to-batch conformity regarding cannabinoid content was noted for all samples of both batches. This may be a consequence of seasonal variation in cannabis plants used for CBD oil production. An inspection of the immediate and outer container labels revealed that the selected CBD oils complied with most labelling requirements stipulated by The Medicines and Related Substances Act, (Act 101 of 1965); with the exception of one CBD oil, which contained no labels besides the proprietary name. South Africa still has many hurdles to overcome in terms of effective cannabis regulation, and measures need to be implemented to ensure unscheduled cannabis products used for medicinal purposes adhere to local regulations. The importance of cannabis education cannot be underestimated; and both cannabis users and health care professionals should be well-informed on clinical and legislative aspects to encourage a sustainable and bright future for the South African cannabis industry.