Cannabis sativa in South Africa: history, legislation, production, and pharmacological aspects

Abstract Cannabis sativa L. has been used for millennia for its textile fibre, its seed oil and as medicine. The South African government recently amended legislation to boost the production of medicinal cannabis which is arguably the most insistent government support for any medicinal plant in South Africa’s history. This review article aimed to collate literature regarding the history of C. sativa in South Africa, its botanical aspects, and ethnopharmacological uses. The current legal situation and the (il)legal production of both medicinal and hemp varieties are described followed by the pharmacological aspects focusing on systematic reviews of clinical trials. Cannabis sativa has a long history in South Africa, as it was widely used before European settlement in 1652. Legal production of medicinal cannabis equates to 587, 4220 and 8505 kg being exported in 2020, 2021 and 2023, respectively. Systematic reviews of clinical trials broadly report inconclusive results but do highlight various deficiencies such as underpowered trial designs, the use of different formulations or modes of administration and adding to this convolution is the introduction of probable bias due to industry sponsorship as well as media hype of many (ongoing) clinical trials. The medicinal value of C. sativa and/or cannabinoids remain difficult to define. A well-designed clinical trial, preferably not sponsored by industry but by academic medical centres or government agencies, using standardised formulations and mode of administration is urgently needed to clarify the complexity of medicinal cannabis.