Sceletium tortuosum is a little succulent plant that grows in the semi-arid Karoo and Namaqualand regions of South Africa. It has a long history of traditional use among the hunter-gatherers of the region.
The plant, known as kanna or kougoed by the San and Khoikhoi people, was mainly chewed or smoked to stay alert and suppress appetite during long hunts. The San were traditionally hunter-gatherers, while the Khoikhoi were pastoralists who herded livestock.
The name kanna (meaning “eland” in the click language of the San), has a symbolic reference to this large antelope, as the “trance animal”, which was called upon during religious and spiritual gatherings. Kougoed is Afrikaans for “something to chew”. The plant can be chewed after being dried and fermented, which is believed to intensify its effects.
The first colonial governor of the Cape colony, Simon van der Stel, in 1685 wrote about kanna in his journal:
They chew mostly a certain plant which they call Canna and which they bruise, roots as well as the stem, between the stones and store and preserve in sewn-up sheepskins.
I’m part of a group of scientists from different disciplines with an interest in this plant and we pooled our expertise to understand its effects on neurochemical concentrations in different parts of the brain.
Our studies were done in mice, so there is caution about establishing effectiveness on humans. Still, the results are striking.
As a chemist with an interest in natural products, I wanted to know which alkaloids in the plant were important in bringing about these effects.
Our latest study explored the effects of Sceletium tortuosum extracts on mouse brain chemistry.
We found that Sceletium increased the levels of certain brain chemicals which may balance mood and reduce stress. These findings lend support to the calming and mood-enhancing use of this plant in traditional medicine.
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Plant chemistry
Our study examined how extracts from different chemotypes of Sceletium tortuosum can have different effects on brain chemistry. Chemotypes are groups of the same plant species that differ in the alkaloids they produce. This is because plants often produce alkaloids in response to external cues such as the weather or the presence of a plant-eating animal or pathogen.
Alkaloids are carbon-based compounds produced by plants. They are often toxic or taste bitter, making the plants less appealing or even harmful to the predators or invaders that want to eat or inhabit them. Alkaloids generally have physiological effects of use to humans. Some commonly used ones include caffeine, morphine and quinine.
We harvested two chemotypes of kanna from the Touwsrivier and De Rust regions of South Africa. These areas were chosen because of their interesting and unusual alkaloid profiles. The chemotypes were given to healthy mice as a supplement once a day for one month. The mice were monitored every day for behavioural or unexpected adverse reactions but none were noted.
At the end of the month, the levels of chemicals in the mouse brain were measured. Both the chemotypes were found to cause a marked increase in noradrenaline and a decrease in GABA in all brain regions studied. Both molecules are neurotransmitters that transmit nerve signals in the brain affecting memory, mood, attention and sleep.
This effect on noradrenaline supports kanna’s traditional use as an appetite suppressing drug. Increased noradrenergic stimulation is also the basis of many anti-depressants as well as drugs that improve attention and alertness.
We also found an impact on the brain chemicals serotonin and dopamine which may act together to balance mood and reduce stress. Serotonin affects emotional well-being and mood; dopamine motivates feelings of pleasure and satisfaction. These findings lend support to the calming and mood-enhancing use of this plant in traditional medicine.
Importantly, the control kanna extracts that did not have the interesting alkaloid profiles did not cause any of these chemical changes in the mouse brain.
Most studies on kanna have focused on the alkaloid mesembrine. The two specific chemotypes of kanna harvested from the Touwsrivier and De Rust regions of South Africa do have the mesembrine, but they are also packed with some other lesser-known or “minor” alkaloids. These differences in alkaloids may arise from a combination of geographic, environmental and inherent genetic factors found in a particular subset of plants.
Both the Touwsrivier and De Rust plants contained higher levels of alkaloids called mesembrine alcohols, which are different from mesembrine, and were barely present in the control extract. Another minor alkaloid, known as sceletium A4, was also identified as possibly being important. Mesembrine alcohols and sceletium A4 may be the ones responsible for the activity.
This suggests that the source of the plant, and the area in which it is grown, can influence its potential as a natural treatment for mood disorders and sleep.
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What the results tell us
Stress, anxiety and depression pose a risk to the ability to lead a meaningful life. The World Health Organization has reported a 25% increase in anxiety and depression worldwide since the emergence of COVID-19.
Our study showed that the plant extracts had a broad noradrenergic effect in mice. But we have to be careful about making connections between results in mice and in humans. We need to explore the behavioural impact of these extracts in both mice and humans, especially in relation to sleep, alertness and mood.
The results also highlighted that without understanding the complex chemical composition of these plants, we risk overgeneralising their benefits, or worse, using them inappropriately.
Our findings have two implications.
First, they point towards a future of precision phytotherapy (use of plants for medicinal purposes), where natural remedies are tailored not just to individuals but to selecting certain plant chemotypes that produce certain combinations of alkaloids. Manipulating the growing conditions and genetic make-up of plants to optimise for alkaloid content is an age-old art.
Second, they remind us of the enormous, still largely untapped potential of African medicinal plants in global health innovation if we invest in research that honours both indigenous knowledge and scientific rigour.
As the world searches for safer, more sustainable ways to treat mental health conditions, South Africa’s kanna plant may hold secrets worth rediscovering.
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