Kanna is an ancient plant that has been revered by the southwestern African people since pre-history. It started gaining popularity in other parts of the world in the seventeenth century and has seen a resurgence of popularity in today’s supplement era. An extract of the Kanna plant is patented under the brand name of Zembrin® since 2012, and it is steadily earning a reputation as a safe cognitive enhancer and anxiety-relieving product.
What is Kanna?
Kanna (Sceletium tortuosum or Mesembryanthemum tortuosum) is also known as Channa, Kougoed, Kauwgoed, Poudre de Sceletium, Racine de Sceletium, and Skeletium. Kanna is a flowering plant with a long history of traditional and folkloric use as chewed leaves or tea.
Belonging to the genus Sceletium in the family Aizoaceae (Mesembryanthemoideae), it grows in the southwestern region of South Africa, primarily in the Northern Cape, Western Cape, and Eastern Cape Provinces. It was once plentiful in Namaqualand in the Northern Cape Province, and the lands in that area were named “Kougoedvlakte,” which translates into “Chewing Stuff Plains”. In the Western Cape Province, the plants were also so abundant that the district of Kannaland was founded there, as “the land of Kanna.” [1, 2, 3, 4]
What is the history of Kanna?
The Khoikhoi people, also known as the Hottentots, are an indigenous ethnic group of southwestern Africans who gave the plant the name of “kanna” in their language of Nama. The Khoikhoi people are nomadic and are grouped together with the hunter-gatherer group San in a compound description of Khoisan. The San people spoke |Xam which is now an extinct language, and their name for kanna was !k”wai or !k”wai:n. The |Xam language is a language of dental clicks which became extinct around 1910. [4, 5, 6]
The first recorded knowledge of the Kanna plant came from Dutch explorers in 1610, but the San people and the Khoikhoi people used Kanna in the ancient pre-history of the African continent. The Dutch explorers and traders found the plant to be so valuable that they named it in their own Dutch language as kaauwgoed and traded it in the Far East. 
The seventeenth-century Dutch explorers and captains thought of kanna as a “Cape ginseng” and sometimes called it ningin root or ningimm root, a slang word for the names of ginseng roots that they had encountered in China and Japan. The East India Trading Company instructed ships that stopped at the Cape on their way to Japan to stock up on food and water and to search for these roots for trading. 
A detailed description from a trading expedition in 1687 wrote that Kanna was found in Namaquaas (Namaqualand) on the mountains and gathered in October; the roots and stem were chewed throughout the day by natives, and it was intoxicating to those tribes who ingested it. 
What are traditional Uses of Kanna?
Though the Dutch who encountered Kanna took note of the euphoric properties of Kanna, the indigenous tribes of Africa used Kanna for many other therapeutic uses. They often fermented the leaves to enhance its psychoactivity by mashing the entire plant until the juices came out, then placed the squashed plant in bags made of animal skins and left the bags out in the sun to ferment for 3 days. After the 3 days, the material inside the bags was stirred and then left for 5 more days in the sun to continue fermenting, after which it was taken from the bags and left outside to dry. Then the dried plant material was twisted, similar to chewing tobacco, or was ground into a fine powder. 
The tribes have used Kanna in rituals, ceremonies, divinations, healings, communal trance dancing events, and ingest it before hunting trips to sharpen the senses. The word for Kanna is the same word they attribute to the antelope, which is considered a magical creature in their culture. The Hottentot tribe combines Kanna with Cannabis sativa for smoking during rituals and communal dancing ceremonies. 
In addition to its sacred uses, the tribes often chew the leaf for pain relief of toothaches and to soothe stomachs. The kanna leaves are drunk as a tea that suppresses hunger and provides pain relief for minor aches and pains. 
What is kanna made of?
Kanna contains bioactive alkaloids responsible for its effects and comprise 1 to 1.5% of its chemical constituents. Modern Western science has not identified all of the structures present within the plant. 
The total alkaloids include:
- Mesembrenine: 2% 
- Mesembrine: when fermented this is converted to Delta-7-mesembrenone
Of the total alkaloids, the major alkaloids that are psychoactive are Mesembrine,
Mesembrenone, Mesembrenol, and Mesembranol. The alkaloids are absorbed through intestinal and oral membranes. The traditional use of chewing Kanna delivers the alkaloids through buccal membrane absorption. 
What are the benefits of Kanna?
Most of the clinical trials and studies involving the Kanna plant involve the Zembrin® extract. Zembrin® is a concentrated extract and 25 mg of Zembrin® equals 50 mg of dried plant mass.  Zembrin® is a GRAS (Generally Recognized As Safe) supplement in the United States. 
Kanna relieves anxiety
this study in 2013 involved a double-blind and placebo-controlled pool of 16 healthy adults that concluded the extract of the kanna plant had anxiety-relieving (anxiolytic) effects.
Kanna may be beneficial for depression
This study focused on in-vitro human cells and concluded that the anti-inflammatory properties of Kanna may be beneficial for cytokine-induced depression
- How does Kanna work for anxiety and depression?
One of Kanna’s most studied benefits is the ability to reduce anxiety. Kanna relieves anxiety by several mechanisms which lead to serotonin reuptake.  Its alkaloids mesembrine and mesembrenone block the 5-HT transporter and inhibit phosphodiesterase 4 (PDE4). 
5-HT reuptake inhibitors are also called SSRI's and are used commonly as pharmaceutical medications to treat anxiety disorders and depression. PDE4 enzymes assist the cyclic AMP (cAMP) cascade and maintain levels of cAMP within the cells. PDE4 can increase the availability of cAMP-response element binding-protein. Depressed individuals often have lower levels of cAMP, and the lower levels of cAMP reflect a downregulation of the cAMP cascade that can often be remedied by using PDE4 inhibitors.
Another mechanism of Kanna for anxiety is its ability to influence the fear reactivity that takes place between the amygdala-hypothalamus coupling in the brain. Kanna reduces subcortical threat responses. The amygdala of the brain is the brain’s threat detection, and it regulates defensive mechanisms in conjunction with the hypothalamus, brainstem, and midbrain. Kanna reduces the connection between the amygdala and hypothalamus so anxiety-induced defense mechanisms are reduced. 
Kanna provides positive mood support
Another double-blind placebo-controlled study in 2014 involved 21 healthy adults and gave them extract of the kanna plant. Positive changes in mood were found.
A study on Kanna’s safety profile unexpectedly encountered an improvement in stress and mood support
Kanna improves cognitive function
this study from 2014 concluded that 25 mg of kanna extract daily for 3 weeks significantly improved cognitive and executive functions
- How does Kanna work to improve cognitive function?
Kanna improves cognitive function because of its ability to inhibit PDE4, specifically its alkaloid mesembrenone. The PDE-coupled cAMP cascade modulates neurogenesis, neuron-microglia reciprocal regulation, and synapse remodeling .
Kanna improves sleep quality
- How Does Kanna work to improve sleep?
Like Kanna’s effects for cognition and mood support, its ability to improve sleep is again centered around the PDE4 inhibition. The PDE4-cAMP-CREB signal cascade regulates the sleep-wake cycle .
Kanna can help with low-grade inflammation
This study was an in-vitro human cell study that concluded Kanna has mild anti-inflammatory properties that can be beneficial for systemic low-grade inflammation but does not interfere with an adequate immune response.
How To Use Kanna
- Encapsulate your own powder
Safety and Side Effects of Kanna
A study from 2013 noted that doses of 8 mg and 25 mg of kanna extract is tolerated well when used by adults once daily for 3 months with no cardiovascular changes in heart rate or blood pressure seen. Side effects included headache, abdominal pain, and upper respiratory tract infections. 
Other anecdotal side effects include loss of appetite, listlessness, and depression. Euphoric side effects and high or excessive doses has resulted in intoxication. Rumors of kanna being hallucinogenic are not substantiated. 
Kanna is non-habit forming based on studies involving rats. The no-observed-adverse-effect-level (NOAEL) in rats were very high doses over a 2-week period that was the equivalent of 5,000 mg/kg of bodyweight. 
Because kanna influences the serotonin pathways in the brain, extra caution is needed when combining kanna with any of the medications, herbs, or supplements that also increase or work on the serotonin receptors or pathways. Using them together can cause serotonin syndrome, which is a serious condition where the brain is overloaded with serotonin and it can be life-threatening.
Kanna should not be combined with SSRI’s or MAOIs, found in anti-anxiety and antidepressant medications (such as Prozac, Zoloft, Cipramil, Seroxat, Fevarin, and many others).
Some herbs and supplements that should not be used with kanna are 5-HTP, L-tryptophan, SAMe, St. John’s wort, Hawaiian baby woodrose, Passionflower, Yohimbe, Syrian Rue, and Banisteriopsis Caapi.
The recreational drug MDMA (ecstasy) should not be used in conjunction with kanna.
- Terburg, David et al. “Acute effects of Sceletium tortuosum (Zembrin), a dual 5-HT reuptake and PDE4 inhibitor, in the human amygdala and its connection to the hypothalamus.” Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacologyvol. 38,13 (2013): 2708-16. doi:10.1038/npp.2013.183
- “Sceletium”. Foods, Herbs, & Supplements. https://naturalmedicines.therapeuticresearch.com/search.aspx?q=Sceletium+tortuosum&go.x=4&go.y=12.
- “Sceletium Tortuosum.” Wikipedia, en.wikipedia.org/wiki/Sceletium_tortuosum.
- Gericke, Nigel. “Kabbo’s !Kwaiń: The Past, Present and Possible Future of Kanna.” McKenna, D. Et Al (Eds.), 2018, pp. 122–150., www.researchgate.net/publication/328942189_Kabbo's_Kwain_The_Past_Present_and_Possible_Future_of_Kanna.
- “Khoikhoi.” Wikipedia, en.wikipedia.org/wiki/Khoikhoi.
- “ǀXam Language.” Wikipedia, en.wikipedia.org/wiki/ǀXam_language.
- “Sceletium Tortuosum – Kanna.” entheology.com/plants/sceletium-tortuosum-kanna/.
- “Sceletium tortuosum”. Examine.com, published Jan 13, 2015. Last updated Jun 14, 2018. https://examine.com/supplements/sceletium-tortuosum/.
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- 11. Simon Chiu, Nigel Gericke, Michel Farina-Woodbury, et al., “Proof-of-Concept Randomized Controlled Study of Cognition Effects of the Proprietary Extract Sceletium tortuosum (Zembrin) Targeting Phosphodiesterase-4 in Cognitively Healthy Subjects: Implications for Alzheimer’s Dementia,” Evidence-Based Complementary and Alternative Medicine, vol. 2014, Article ID 682014, 9 pages, 2014. https://doi.org/10.1155/2014/682014.
- Nell, H, et al. “A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Trial of Extract Sceletium Tortuosum (Zembrin) in Healthy Adults.” J Altern Complemnt Med, vol. 19, no. 11, Nov. 2013, pp. 898–904., doi:10.1089/acm.2012.0185