Sceletium Tortuosum

Sceletium tortuosum, now also classified as Mesembryanthemum tortuosum and popularly called kanna, is a succulent forb in the family Aizoaceae that is endemic to the Cape region of South Africa ^[1]. Its pharmacology is driven by a group of mesembrine-type alkaloids, of which around twenty-five have been described across several structural classes, with mesembrine, mesembrenone, and mesembrenol among the most important ^[1]. In fresh plant material mesembrine tends to predominate ^[1].

The plant has a long ethnobotanical history. Indigenous San and Khoikhoi peoples used it for centuries as a masticatory and medicine, chewing or fermenting the plant to relieve thirst, hunger, and fatigue, to ease pain, and for social and spiritual purposes, with the earliest written record dating to the seventeenth century ^[1]. Traditional preparation often involves a fermentation, or bruising and drying step, which shifts the alkaloid balance and is thought to enhance the psychoactive effect ^[1].

Modern interest centers on the plant's effects on mood and stress. Laboratory studies show that a standardized extract inhibits the serotonin transporter and, distinctively, also inhibits phosphodiesterase 4, a dual action that has been proposed to underlie its anxiolytic and antidepressant potential ^[2]. Some work suggests that high-mesembrine extracts act primarily as monoamine-releasing agents, upregulating the vesicular monoamine transporter, with serotonin-reuptake inhibition a secondary effect ^[3].

Clinical research has largely used the proprietary extract Zembrin. A three-month randomized, double-blind, placebo-controlled study in healthy adults found it well tolerated, with some participants reporting improved coping with stress and sleep ^[4]. A pharmaco-fMRI study reported that a single dose reduced reactivity of the amygdala, a brain region involved in threat processing, and weakened its coupling to the hypothalamus, offering a neurobiological rationale for anxiolytic effects ^[5]. Reviews note that clinical testing so far has been mainly in healthy volunteers, so evidence in diagnosed anxiety or depression remains limited ^[1].

Kanna is available as dried plant material, teas, tinctures, capsules, and standardized extracts, and it can be chewed, brewed, or taken as a snuff ^[1]. It is sold as a botanical supplement rather than an approved medicine. Animal and human safety data to date are reassuring at the doses studied, though caution is advised about combining it with serotonergic drugs ^[1][4].

Traditional use is long and reassuring, and standardized extracts have looked well tolerated in small trials. The same serotonergic caution applies: do not combine with SSRIs, SNRIs, MAOIs, or other serotonin drugs. Mild nausea, headache, or appetite changes are the usual complaints. It is sold as a supplement in many places.