Mesembryanthemum tortuosum and Zembrin: Mixed Evidence from In vivo Animal and Clinical Studies on their Antidepressant and Anxiolytic Effects

<i>Mesembryanthemum tortuosum</i> is a succulent plant native to southern Africa and was traditionally used to enhance mood. Recent research into <i>M. tortuosum</i>'s mood-enhancing effects has culminated in the development of a standardised extract, Zembrin, containing consistent levels of mesembrine alkaloids considered to be the main bioactive compounds. This review aims to critically investigate published <i>in vivo</i> animal and clinical studies using <i>M. tortuosum</i>, Zembrin, and mesembrine alkaloids, to evaluate the study designs, formulations, and dosages used, and to assess the results in terms of safety and therapeutic efficacy as an antidepressant and anxiolytic. Four databases, namely PubMed, Scopus, Web of Science, and ScienceDirect, were searched using terms relating to 'clinical trials', '<i>in vivo</i>', '<i>Mesembryanthemum</i>', '<i>M. tortuosum</i>', 'pre-clinical', 'Sceletium', '<i>S. tortuosum</i>', and 'Zembrin'. The search was conducted to identify original research articles published before July 2025. Although published pre-clinical animal and clinical studies on <i>M. tortuosum-</i>derived products offer valuable insights, such as a favourable safety profile and potential efficacy as an anxiolytic and antidepressant, several limitations have been identified, including small sample sizes and studies conducted in clinically irrelevant populations. A limited number of reported outcomes suggest that Zembrin may have positive effects on anxiety, cognitive function, stress resilience, and mood. However, not all studies showed consistent benefits, and some outcomes were limited to specific measures such as EEG changes or reaction time under cognitive stress. Large-scale clinical trials in relevant populations should be conducted to determine the potential of <i>M. tortuosum</i>-derived products as anxiolytics and antidepressants.