What is Sceletium Tortuosum (Kanna)?
Sceletium tortuosum is a South African succulent plant. Local people traditionally ferment the plant into its medicinal form – called kanna, channa, or kougoed – and chew it to relieve hunger, thirst, and pain. Centuries-old reports of its use describe hunters and farmers washing their aching legs with kanna. Kanna is also a psychoactive herb: it is used to reduce anxiety and stress, but it is neither hallucinogenic nor addictive [1, 2, 3].
- Promotes feelings of calm and focus
- May relieve pain
- Suppresses hunger
- Long history of traditional use
- Safe at all tested doses
- Can be grown as a houseplant
- Very limited modern research pool
- Will not work for everyone
- May cause nausea in first-time users
- Potentially dangerous drug interactions
- Significant risk of bias in clinical studies
Kanna’s most important chemical compounds are alkaloids: mesembrine, mesembrenone, mesembrenol, mesembranol, epimesembranol, and tortuosamine. Of these, mesembrine and mesembrenone are thought to be the most active [5, 6].
Potential Benefits (Possibly Effective)
Kanna has produced positive results in multiple studies investigating these benefits, but larger and more robust studies are required to confirm its effectiveness. Furthermore, some of these studies are at significant risk of bias. Talk to your doctor before using kanna.
Mesembrine and complete Sceletium tortuosum extract may work as natural antidepressants. In clinical studies, people who took Sceletium tortuosum (as Zembrin, the most common commercially available extract) reported improved sleep and reduced stress. In rats, a purified extract of Sceletium tortuosum was about half as effective as imipramine, a tricyclic antidepressant drug [7, 8].
A few psychiatric doctors in South Africa prescribe kanna to patients with depression, mild depression (dysthymia), and anxiety. These reported case studies have been successful; in some cases, patients have responded better to kanna than to conventional antidepressants like citalopram [9, 10].
Note, however, that these case studies are limited and likely biased: the doctor reporting them has a long history of studying traditional African medicine, but he is also credited as the Medical and Scientific Director of the company that sells Zembrin. He has a clear financial incentive to promote the supplement [9, 10].
Kanna’s mechanism of action appears very similar to many prescription antidepressant and anti-anxiety medications. In cell studies, kanna acts very similarly to medications like Prozac, Zoloft, Cymbalta, increasing the amount of serotonin available .
In a cell study, a Sceletium tortuosum extract rich in mesembrine decreased the stress hormone cortisol. Researchers suggested that the extract may be useful in people with high stress and high blood pressure; these results have yet to be verified in animal or human studies .
Inflammation and Depression
Depression and inflammation are closely linked, and some cases of depression may be caused by high levels of inflammatory molecules called cytokines. In one study, cells exposed to Sceletium tortuosum extract increased expression of IL-10, a unique cytokine that lowers inflammation and reduces the expression of other inflammation-promoting cytokines .
In this way, kanna protected immune cells and reduced the inflammatory response, which may partially explain its antidepressant properties. However, this effect has yet to be observed in animal or human studies.
In psychology, “executive function” describes a person’s ability (or lack thereof) to plan, solve problems, and complete tasks. Mental illness and psychiatric disorders often damage a person’s executive function: depression, anxiety, autism, and even obesity all reduce our ability to get things done [13, 14, 15, 16, 17].
Early clinical research suggests that kanna may improve executive function and cognitive flexibility. In one study, people enjoyed significant increases in these two areas after supplementing with 25 mg/day of kanna for 9 weeks. Unfortunately, this study only recruited 35 healthy adults between the ages of 45 and 65; larger studies with more varied people will demonstrate whether this benefit is significant .
Alzheimer’s disease is marked by a significant decrease in cognition; researchers have identified phosphodiesterase 4, or PDE4, as a possible target for new Alzheimer’s medication. Because of its ability to block PDE4, some researchers believe that kanna may alleviate early symptoms of Alzheimer’s. There have not yet been any clinical trials to determine whether this hypothesis plays out in reality [18, 10].
Traditional Use (Lacking Evidence)
No clinical evidence supports the use of kanna for any of the conditions listed in this section. Below is a summary of the existing animal research and traditional use, which should guide further investigational efforts. However, the studies listed below should not be interpreted as supportive of any health benefit.
According to traditional medicine and animal studies, kanna is an effective natural painkiller. In a rat study, mesembrine from kanna was slightly less effective than the strong opioid morphine. Traditional practitioners would rub kanna on the aching legs of hunters and farmers, and pregnant women would chew it to soothe their aches and pains. They would even give drops of kanna to crying babies to help them sleep [19, 20].
High doses of kanna activate opioid receptors in the brain, so this evidence of painkilling properties is not surprising. We naturally produce opioids – endorphins and enkephalins – to soothe feelings of pain and boost sensations of reward and pleasure. Other compounds that bind to opioid receptors include morphine and oxycodone; unlike these prescription painkillers, kanna does not appear to be addictive [21, 22].
Kanna’s active compounds bind to the receptor for cholecystokinin-1. This receptor, when activated, reduces the sensation of hunger; kanna may, therefore, help stop people from overeating. Historical records support this potential effect: two sources from the early 1900s report that kanna decreases appetite and hunger. However, no modern studies have investigated this claim [21, 23, 20].
Mechanism of Action
Serotonin Reuptake Inhibition
Low serotonin levels or activity in certain parts of the brain can worsen mood and may lead to depression. On the other hand, activating specific serotonin receptors can trigger a psychedelic state with powerful feelings of mysticism and importance [24, 25, 26].
Mesembrine from kanna is a serotonin reuptake inhibitor: it prevents serotonin from being absorbed and hidden away in the neurons. This could potentially allow serotonin to stay active for longer and have a stronger effect on the brain. This may also explain the mind-expanding effects of kanna some users report, although these have not been scientifically confirmed .
Vesicular monoamine transporter 2, or VMAT2, is a protein that transports neurotransmitters out of the cell, where they can have their effects. In the brain, VMAT2 transports – and thereby activates – molecules like dopamine, serotonin, and GABA .
One study suggests that mesembrine increases the activity of VMAT2. If true, then kanna may increase available serotonin in two ways: by increasing the amount of serotonin released by each cell and by decreasing the amount reabsorbed .
VMAT2 releases a variety of different neurotransmitters in different parts of the brain; kanna’s effects on these other molecules has not been studied .
In addition to increasing serotonin, mesembrenone also boosts energy use in the body by blocking an enzyme called phosphodiesterase 4, or PDE4 .
PDE4 breaks down a messenger molecule called cyclic adenosine monophosphate, or cAMP. cAMP is crucial for energy balance – it is among the key metabolic controllers in cells. cAMP increases fat-burning and acts on glucagon, adrenaline, and immune cells. It also activates a pathway that forms long-lasting memories [29, 30, 31, 32, 33, 34].
When mesembrenone blocks PDE4, it makes more cAMP available for longer in the blood and increases cAMP’s effects.
GABA calms brain activity and can decrease anxiety; natural opioids kill pain and create a sense of wellbeing; cholecystokinin reduces hunger and prevents inflammation in the gut, and melatonin improves sleep quality. Prostaglandins are complex molecules, but the receptor Sceletium activates (EP4) may support gut health and prevent whole-body inflammation [35, 5, 36, 37, 38, 39, 40].
High doses of either Sceletium or mesembrine were used to trigger such wide-spread activation in rats. These effects have not been observed in human trials.
Safety Considerations & Drug Interactions
Kanna is considered relatively safe. No side effects are expected up to a dose of 6 mg per kg of body weight per day, or 420 mg in an average adult human; however, some people may experience nausea when they start to use the herb. According to traditional practitioners, most people get used to kanna after one or two doses .
There have been no toxicology studies on the safety of giving kanna to children. Traditional practitioners give small amounts of kanna to infants to help them sleep, but we recommend strongly against this without sufficient safety data. Talk to your doctor before giving any bioactive supplements to children [20, 42].
Likewise, pregnant women traditionally chewed kanna to relieve nausea and indigestion. However, as with children, the safety profile of kanna in pregnant or breastfeeding mothers has not been studied. We therefore recommend caution .
According to both traditional knowledge and rat studies, kanna is unlikely to be addictive. Rats do not actively seek out the herb like they would seek out an addictive drug; in multiple anecdotal reports, people have suddenly stopped taking kanna with no adverse effects or withdrawal symptoms [21, 20].
Kanna and Pets
One Japanese research group studied kanna’s safety for cats and dogs and found no toxic effects at a dose of 10 mg per kg of body weight per day in dogs and 100 mg/kg/day in cats .
10 mg/kg is equivalent to 227 mg for a 50 pound dog; 100 mg/kg is equivalent to 454 mg for a 10 pound cat. No studies have found any benefit to giving kanna to dogs or cats, so we don’t recommend giving it to them on purpose; however, if your companion accidentally ate some, he or she is probably fine. Watch for signs of poisoning like vomiting, diarrhea, and lack of energy; contact your vet if at the first sign of illness .
Too much serotonin in the nervous system can cause a condition called serotonin syndrome. In minor cases, people experience symptoms like tremor, twitching, anxiety, insomnia, and increased heart rate. If serotonin levels get high enough, this syndrome can cause seizures, delirium, and extremely high body temperature. In extreme cases, a person suffering from serotonin syndrome can fall into a coma. The symptoms of this condition vary from person to person, and they range from mild to life-threatening [44, 45].
Many antidepressants work primarily by increasing the amount of available serotonin in the brain. Similarly, kanna increases available serotonin; it may be dangerous in people who are already taking antidepressant medication [25, 46, 5].
Monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), and serotonin and norepinephrine reuptake inhibitors (SNRIs) should not be combined with kanna.
This class of drugs includes :
This class of drugs includes:
If you are taking any medication for depression or anxiety, talk to your doctor before using kanna.
Kanna is a serotonin reuptake inhibitor, like the SSRIs listed above. Such medications interact dangerously with many other substances, such as :
- St. John’s Wort
We recommend caution when combining bioactive supplements with medication. Talk to your doctor to avoid adverse effects and unexpected interactions.
Genetics of Response
Genes Affecting Serotonin
Many researchers have investigated the interaction of SSRIs with genetics. Because kanna shares a mechanism with this class of drugs, the genes that affect SSRIs may affect kanna in a similar way. Note, however, that these genes have not been connected specifically to kanna; more research is required to confirm any direct interactions .
- GCHFR produces a protein that helps make serotonin and dopamine. People with two copies of the T allele at rs7163862 produce less serotonin and may have a weak response to kanna .
- TPH1 produces a protein that helps make serotonin. People with one or two copies of the A allele at rs1800532 produce less serotonin and may have a weak response to kanna .
- TPH2 produces a protein that controls serotonin production in the brain. People with one C and one T allele at rs2171363 respond better than those with two C’s or two T’s to some SSRIs; they may also respond better to kanna. People with at least one C allele at rs10897346 are less likely to respond to SSRIs and may have a weak response to kanna [56, 55].
- HTR1A produces one of the serotonin receptors. People with two copies of the G allele at rs1364043 respond better to some SSRIs and may also have a stronger response to kanna. People with two copies of the G allele at rs6295 do not respond as well to some SSRIs and may have a weaker response to kanna .
- HTR1B produces one of the serotonin receptors. People with two copies of the C allele at rs6298 respond better to some SSRIs and may also have a stronger response to kanna. People with two copies of the G allele at rs6296 do not respond as well to some SSRIs and may have a weaker response to kanna .
- HTR2A produces one of the serotonin receptors. People with two copies of the A allele at rs7997012 are more likely to respond to some SSRIs; people with two copies of the G allele at this SNP are less likely to respond to some SSRIs. These people’s response to kanna may be similar. People with two copies of the C allele at rs6311 are more likely to experience sexual dysfunction when taking SSRIs and may wish to be cautious when using kanna .
- SLC6A4 produces the serotonin transporter protein. This protein moves serotonin out of the synapse and back into the neuron, making it unavailable and ineffective. SLC6A4 is varied and complicated: part of this gene can be short (S) or long (L), and people with the L allele can have either the A or G subtype (sometimes written LA and LG) at rs25531. People with the S or LG alleles produce less of this transporter protein; these people have a weaker response to some SSRIs and may also have a weaker response to kanna. People with the LA allele respond better to some SSRIs and may have a stronger response to kanna .
- COMT produces an enzyme that breaks down dopamine and other catecholamines. The dopamine and serotonin systems are very closely linked; people with at least one A allele at rs4680 respond better to some SSRIs and may have a stronger response to kanna .
In pop culture, VMAT2 (or the SLC18A2 gene) has the reputation of being the “God gene” that influences whether a person is likely to be religious or spiritual. This claim is highly controversial, but SLC18A2 certainly affects the amount of dopamine stored, released, and available in the brain [57, 58].
This gene codes for the VMAT2 protein. In one study, kanna increased the amount of the VMAT2 protein in human and mouse cells. Certain variations near the SLC18A2 gene can also increase and decrease VMAT2 expression, which may affect how a person experiences kanna’s effects [28, 59].
Scientists explored a region near the SLC18A2 gene that affects its activity (promoter region). Some combinations of variants can increase the expression of this gene, while one combination of variants can decrease it .
Increased SLC18A2 expression may protect against Parkinson’s disease in women. People who have higher gene activity may also be more sensitive to the psychoactive effects of kanna; people with lower VMAT2 transcription may benefit more from kanna, as this herb may raise VMAT2 levels in their brains (and potentially offer some protection against cognitive dysfunction) .
However, only one of the researched SNPs (rs60912143) has an RSID number. Studies are still underway and this newly discovered SNP is not available in commercial DNA tests. However, affordable whole-genome sequencing may make this data available to consumers in the near future .
Supplementation & Dosage
The most widely available commercial form of kanna is Zembrin. Zembrin is a standardized extract of Sceletium tortuosum; it is sold as a powder and in single-dose capsules. Multiple companies sell Sceletium tortuosum as an extract or in tea.
Alternatively, you may be able to find Sceletium tortuosum sold as a houseplant. This succulent shrub can be grown from seed or bought as a seedling and re-potted. When it’s mature, the whole plant can then be fermented and dried. The fermentation process changes the chemical profile of the herb, increasing mesembrine and decreasing mesembrenone .
The smell of kanna is compared to that of tobacco and its taste described as very bitter. Traditional healers warn that fermented kanna should only be chewed for about 15 minutes and then removed from the mouth. Any longer than that and the user will become intoxicated .
The recommended dosage of Zembrin, a commercial Sceletium tortuosum extract, is 25 – 50 mg per day for cognitive effects. Some South African psychiatrists prescribe kanna for major depression and anxiety; these patients receive between 100 – 200mg per day, taking half with breakfast and half with lunch [61, 62, 41, 20].
In a rat toxicology study, researchers concluded that up to 6 mg per kg of body weight per day would be completely safe to consume. For an average adult human, that works out to 420 mg per day, far above the effective dose .
According to tradition, fermented kanna should be chewed for about 15 minutes and then removed from the mouth for the best result. If chewed for longer, they say, it will intoxicate the user .
Limitations and Caveats
Much of the traditional knowledge of Sceletium tortuosum has either been lost or has yet to be scientifically verified. Of the work that does exist, a significant proportion belongs to a single researcher for whom kanna and other traditional South African medicines are a passion project. While his work and interest predate any corporate partnership, he is currently a Director of the company that makes Zembrin, a commercial extract of Sceletium tortuosum. This company, HG&H Pharmaceuticals, funds a large proportion of current research on kanna.
Research on kanna’s beneficial effects is in its preliminary stages. Effects which have been demonstrated in cell studies may not have been tested in live animal or clinical human studies. Some clinical human studies, furthermore, suffer from small sample sizes. Anecdotal reports of some benefits are, by their nature, selective: only the success stories are presented.
Kanna is the fermented product of the whole Sceletium tortuosum plant: a small succulent that grows wild in South Africa. Kanna’s active components, mesembrine and mesembrenone, may act as natural serotonin reuptake inhibitors, increasing the amount of available serotonin in the brain.
Kanna has antidepressant and anti-anxiety properties and may improve executive function and cognitive flexibility. It is traditionally used as a mild painkiller and to decrease appetite. It is recognized as safe, with few reported side effects even at large doses; however, some people may get nauseated the first time they use this herb. Kanna has not been demonstrated to be addictive.
Because kanna is a serotonin reuptake inhibitor, it should not be mixed with other serotonin reuptake inhibitors. Too much serotonin in the body can result in serotonin syndrome, a potentially life-threatening condition. Use caution when combining kanna with any substance that affects serotonin, including SSRIs and antipsychotic medication. Many genes influence the body’s response to serotonin reuptake inhibitors. These genes may also affect how you experience kanna.