Chemistry & Pharmacology

Sceletium Kanna Alkaloid Chemistry

Sceletium Chemistry

Sceletium has possibly the most complex chemistry of any ethnobotanically significant plant in the world with at least 32 known alkaloids (including a number of terpenes and saponins) isolated from the genus to date. As follows:

Sceletium Alkaloids 1

Sceletium Alkaloids 2

The range of phenolic alkaloids in Sceletium tortuosum belong to the crinane class of compounds and fall into four distinct structural categories defined by their alkaloid skeletal type:

(1) The 3a-aryl-cis-octahydroindole class (e.g. mesembrine)
(2) The C-seco mesembrine alkaloids (e.g. joubertiamine)
(3) Alkaloids containing a 2,3-disubstituted pyridine moiety and 2 nitrogen atoms (e.g. sceletium A4)
(4) A ring C-seco Sceletium alkaloid A4 group (e.g. tortuosamine).

The dominant, and clinically significant, alkaloids in Sceletium tortuosum are mesembrine, mesembrenone, ∆7-mesembrenone, mesembrenol and tortuosamine, though the minor alkaloids undoubtedly play important roles in the overall pharmacological effect too.

There is great variability in the distribution and concentration of both major alkaloids and minor alkaloids due to factors such as cultivar, season, geographical and climatic factors, growing conditions and age – and differences have even been noted between two plants growing right next to each other in the wild. Alkaloid levels are generally considered best in the late spring to early summer when the plants are fruiting.

Furthermore the process of bruising and fermentation significantly alters the alkaloid profile, which we will deal with in some detail below. All that said, total alkaloid levels can range between 0.3% and 2.3% of dry weight. The average for cultivated material is generally around 0.8% total alkaloids, though there are certain high-yield stains that have been developed that can average double that.

Some, including ethnobotanist Christian Rätsch, believe that it is possible that tryptamines may occur in Sceletium tortuosum. However, we believe this to be unlikely as (a) it has never been demonstrated, (b) the general chemical profile of the plant does not suggest this possibility and (c) careful bio-assay does not indicate the presence of tryptamines.

Fermentation

In traditional usage by the Khoisan, Sceletium has always been fermented in the process of producing the original Kougoed, and there has been much speculation, even among researchers in this field, as to the reasons, usefulness and efficacy (or not, as the case may be) of this process. Hopefully the following information will shed some light on the matter.

Bruised Kanna

In the traditional context, the freshly harvested Kanna, would be bruised (normally by crushing between two stones) and then placed in a gourd made from animal skins, or, in more recent times, in a plastic bag or glass jar. This would then be left out in the sun and allowed to ferment for a period of somewhere between 5 and 8 days. After this fermentation process, the Kanna would then be placed out in the sun to dry to produce the traditional Kougoed. It has also been stated that without this fermentation there is no power in the plant (which is not entirely true).

A number of critical papers address the matter of fermentation:

Together, these papers show clearly some of the effects that fermentation has on the alkaloid profile, and further independent research subsequent to this has also verified these findings.

In summary, the fermentation of Kanna accomplishes the following primary outcomes:

  • Lowers oxalic acid
  • Lowers 4′-O-demethylmesembrenol
  • Significantly converts mesembrine to mesembrenone and ∆7-mesembrenone
  • May increase total alkaloid levels (by a very small measure)

(For reference, the traditional fermentation process which leads to this, as described verbatim by a local informant from the Namaqualand area (Smith at al. 1996) was “Leave the bag of crushed Kougoed in the sun to get warm; it’s not necessary to put it in the shade, it gets shade at night, and the sun doesn’t harm it. The plant is left to sweat. After 2 to 3 days the bag is opened, the Kougoed is mixed around, and then the bag is tightly closed again. On the eighth day after the crushing, the bag is opened and the Kougoed is spread out to dry in the sun, as when you dry raisins. You leave it out until it is dry. If you don’t do the whole thing, the plant won’t have power. If you eat the fresh plant nothing will happen – it doesn’t have power. I learned to prepare it from my father”. In the experiments referenced in these papers this process was mimicked under controlled laboratory conditions.)

It is also evident from studying the above research that this is not all that is going on, and that there is a complexity, beyond our full comprehension at this stage, related to all the alkaloidal transformations that occur during the fermentation process.

It also appears from the Journal of Pharmaceutical Biology paper that the mere act of bruising and crushing the plant, followed by drying at 80°C produced a very similar alkaloid profile to that which developed during full fermentation. This suggests, quoting directly from that paper, that “It is possible that, on crushing, enzymatic reactions may take place following cellular decompartmentation, these reactions may explain the modification of the alkaloid ratio and concentration that is observed in crushed plant material dried at 80°C; a temperature at which these reactions may be greatly amplified. From the results of this experiment it would seem that the essential step in the production of Kougoed may not entirely revolve around fermentation but that the crushing of the plant material and consequently the mixing of cellular material may be equally essential”.

This gives scientific credibility to another traditional method of Kougoed production referenced in the 1996 Journal of Ethnopharmacology review article on Sceletium in which it is stated that “A second informant described an alternative preparation technique, employed when the user seeks to rapidly prepare Kougoed. A small fire is made over sand, and when it dies down, the ashes are scraped aside, and a hollow made in the sand. A freshly picked, whole Sceletium plant is placed in this excavation, and covered with hot sand. An hour later the baked plant product is recovered, reputedly with acquired properties similar to the conventionally prepared material”.

It is also important to qualify the statement above that “fermentation converts mesembrine to mesembrenone and ∆7-mesembrenone”. This seems plausible, but what the data actually shows is that mesembrine levels decrease and that mesembrenone and ∆7-mesembrenone (double-bond isomers of each other) levels increase. So while this suggests “conversion” from the one alkaloid to the other as the “cause”, some other mechanism could be at play. Altogether very interesting stuff – and more detailed research into these phenomena are clearly called for.

Finally for the flavour aficionados, fermenting Kanna does some richly interesting stuff to the taste and aroma, which many smokers and chewers appreciate!

fermenting kanna

Oxalates

Oxalic acid is an organic compound commonly found at high levels in members of the spinach family, the brassicas (cabbage, broccoli, brussels sprouts, kale, rocket), sorrel, rhubarb and umbellifers like parsley. It also occurs in green bell peppers, beet greens, chives, leeks, purslane, dandelion, almonds, chocolate and… Sceletium.

It is a colorless crystalline solid that forms a clear solution in water and is a slightly stronger acid than acetic acid (vinegar). It is normally contra-indicated for those suffering from kidney stones, renal insufficiency, gout and rheumatoid arthritis (though some modern research is already questioning this traditional point of view). Excessive oxalic acid can also be a gastric irritant and contribute to joint pain due to calcium oxalate deposists.

An analysis on unfermented dry Sceletium using the technique of Sutikno et al. (1987) has indicated levels of 3.6% – 5.1% oxalate. This falls within the median range for oxalates in crop plants reported by Libert and Franceschi (1987). By contrast, common high oxalate foods are parsley (1.7%), chives (1.5%), beet greens (1.0%), spinach (0.8%) and cacao (0.6%).

On the other side, oxalic acid is needed by the body and  is important for colon health. When we do not get enough from our diet, the body makes it from ascorbic acid. All the foods that are high in antioxidants are also high in oxalic acid, and cancer is always associated with low levels of oxalic acid in the blood.

Observations and reports by Watt and Breyer-Brandwijk (1962), Kellerman et al. (1988) and Smith et al. (1996) regarding oxalates in Sceletium have suggested that the physical crushing of the plant and the fermentation process may, in some way, ameliorate the levels of oxalic acid. Free oxalic acid is likely to complex with cell-wall-associated calcium salts and precipitate as calcium oxalate when plant material is crushed.

Oxalates are degraded by microbial populations in the gastrointestinal tract of humans, ruminants and non-ruminant herbivores (Daniel et al., 1987). There is evidence that adaptive changes in microbial microflora may reduce oxalate absorbtion and toxicity (Argenzio et al., 1988). Allison et al. (1985) have proposed that these anaerobes be named Oxalobacter formigenes and it has been suggested that soils and lake sediments may serve as an inoculum for oxalate degrading organisms in the digestive tract of animals (Smith et al., 1985). Smith et al. (1996) suggest that the crushing process, prior to anaerobic fermentation would introduce oxalatedegrading microbes into the skin or plastic bag and so ameliorate levels of oxalic acid. The use of Mesembryanthemaceae to initiate fermentation for alcohol or breadmaking is well documented (Juritz, 1906; Watt and Breyer-Brandwijk, 1962), so that the microbiology of fermentation in Kougoed is likely to be quite complex.

The alternate preparatory method for Kougoed mentioned above involving burying plant material in hot sand may also have a scientific basis. Oxalic acid is a simple dicarboxylic acid, and considerable sublimation is likely to occur at temperatures above its melting point of 101-102°C; on the other hand, mesembrine only boils between 186-190°C (Merck Index). Hence the use of this simple physical technique may achieve the same result as the more traditional fermentation process by removing oxalates, and drying the material while retaining alkaloids.

In summary, it is evident that fermentation decreases levels of oxalates in Kanna. It is also evident that the level of oxalic acid in Kanna (given the daily or occasional dose that is used) compared to what is normally ingested from common founds, is negligible (500mg of unfermented Sceletium per day being the equivalent of 3g of spinach), and of no consequence at all except perhaps in the managing of severe cases of renal insufficiency.

Pharmacology

Coming soon 🙂

Sourcing & Cultivation…/