Sceletium tortuosum is a succulent plant commonly found in South Africa, which is also known as Kanna, Channa, Kougoed (Kauwgoed/ 'kougoed', prepared from 'fermenting' S. tortuosum)—which literally means, 'chew(able) things' or 'something to chew'.
The generally recognised eight Sceletium species are S. crassicaule, S. emarcidum, S. exalatum, S. expansum, S. rigidum, S. strictum, S. tortuosum and S. varians. Per Klak et al. (2007), an alternative classification for the Sceletium group is Mesembryanthemum crassicaule, M. emarcidum, M. exalatum, M. expansum, M. archeri (S. rigidum), M. ladismithiense (S. strictum), M. tortuosum and M. varians.
The plant has been used by South African pastoralists and hunter-gatherers as a mood-altering substance from prehistoric times. The first known written account of the plant's use was in 1662 by Jan van Riebeeck. The traditionally prepared dried Sceletium was often chewed and the saliva swallowed, but it has also been made into gel caps, teas and tinctures. It has also been used as a snuff and smoked.
S. tortuosum is traditionally used to fight stress and depression, relieve pain and alleviate hunger.
S. tortuosum contains about 1–1.5% total alkaloids. The alkaloids contained in S. tortuosum believed to possess psychoactivity include mesembrine, mesembrenone, mesembrenol and tortuosamine. A standardised ethanolic extract of dried S. tortuosum had a IC50 for SERT of 4.3 μg/ml and for PDE4 inhibition of 8.5 μg/ml.
Mesembrine is a major alkaloid present in S. tortuosum. There is about 0.3% mesembrine in the leaves and 0.86% in the leaves, stems, and flowers of the plant. It serves as a serotonin reuptake inhibitor with less prominent inhibitory effects on phosphodiesterase 4 (PDE4). In an in vitro study, a high-mesembrine Sceletium extract showed monoamine releasing activity by upregulation of vesicular monoamine transporter 2 (VMAT2).
Mesembrenone on the other hand serves as a more balanced serotonin reuptake inhibitor and PDE4 inhibitor.
Traditional and contemporary methods of preparation serve to reduce levels of potentially harmful oxalates found in S. tortuosum. An analysis indicated levels of 3.6-5.1% oxalate, which falls within the median range for crop plants, just like spinach or kale. It is speculated that physical crushing of the plant and the fermentation process reduce the potentially harmful effects of oxalic acid. In particular, free oxalic acid is likely to complex with cell wall-associated calcium salts and precipitate as calcium oxalate when plant material is crushed.
No treatment-related adverse effects were observed in an oral toxicity study in rats of a standardized hydroethanolic extract of S. tortuosum. The extract, although not mesembrine itself, produced ataxia in rats, thereby possibly limiting the usefulness of the extract as an antidepressant.
The long history of traditional human use suggests but does not prove that S. tortuosum is relatively safe for human consumption. Use of the 2:1 standardised extract in healthy adults at a dose of up to 25 mg once daily over a three-month period was well tolerated.
VMAT-2 was upregulated significantly in response to Sceletium treatment. The extract showed only relatively mild inhibition of AChE and MAO-A. We conclude that the serotonin reuptake inhibition activity ascribed to the Sceletium plant, is a secondary function to the monoamine-releasing activity of high-mesembrine Sceletium extract (TrimesemineTM).
No mortality or treatment-related adverse effects were observed in male or female Crl:(WI)BR Wistar rats in the 14- or 90-day studies. In the 14- and 90-day studies, the NOAELs were concluded as 5000 and 600 mg/kg bw/d, respectively, the highest dose groups tested.
Mesembrine appears to have analgesic properties without abuse liabilities or ataxia. The Sceletium tortuosum fraction has antidepressant properties but does produce ataxia. The ataxia may limit its usefulness as an antidepressant unless the antidepressant activity is associated with one constituent and the ataxia is associated with a separate constituent.
Both doses of extract Sceletium tortuosum (Zembrin) (8 mg and 25 mg) were well tolerated when used by healthy human subjects once daily for 3 months.