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.
Kanna is traditionally used to fight stress and depression, relieve pain and alleviate hunger and it has been studied to alleviate excessive nocturnal barking in dogs, or meowing in cats, in pets diagnosed with dementia.
Kanna may elevate mood and decrease anxiety, stress and tension. Intoxicating doses can be euphoric but not hallucinogenic, contrary to some literature on the subject.
Kanna contains about 1–1.5% total alkaloids. The alkaloids contained in Sceletium tortuosum believed to possess psychoactivity include mesembrine, mesembrenone, mesembrenol and tortuosamine. A standardised ethanolic extract of dried S. tortuosum had an IC50 for SERT of 4.3 μg/ml and for PDE4 inhibition of 8.5 μg/ml. Kanna is also reported to be an acetylcholinesterase inhibitor and cannabinoid agonist.
Mesembrine is a major alkaloid present in kanna. There is about 0.3% mesembrine in the roots 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.