Mesembryanthemum tortuosum L. (Aizoaceae) was previously classified as Sceletium tortuosum and is still widely referred to under that name in literature. Locally, the plant is known as ‘kanna’. The small scrambling succulent is endemic to South Africa and is found in the arid areas of the Western, Eastern and Northern Cape provinces. For centuries, the Khoi and San people used the aerial parts in the form of a masticant or infusion, as a mood enhancer, to promote sleep and to soothe digestive conditions. After traditional fermentation to boost its psychoactive properties, the remedy is referred to as ‘kougoed’. The plant has been fully commercialised and selected chemotypes are cultivated as a source of raw material. Products are used for the management of mild depression, anxiety, insomnia, weak appetite, stress, bulimia, obsessive compulsive disorder and to alleviate drug-dependence. The psychoactive properties of the plant are attributed to the presence of mesembrine-type alkaloids. This monograph is a record of the ethnobotany, and the extensive research carried out to study the phytochemistry, in vitro and in vivo biological and pharmacological properties of M. tortuosum, as well as its toxicity profile. High-performance thin-layer chromatography (HPTLC) and ultra-performance liquid chromatography coupled to mass spectrometry (UPLC-MS) were used to establish typical chemical fingerprints of the plant. The marker compounds, mesembrenol, mesembranol, mesembrenone and mesembrine, were identified after both HPTLC and UPLC-MS analyses. © 2023 Elsevier Inc. All rights reserved.