Kanna alkaloids

Chemical studies have indicated a broad range of phenolic alkaloids in Sceletium tortuosum which fall into three distinct structural categories defined by their skeletal type: alkaloids of the mesembrine-family, alkaloids of the joubertiamine family and a third variant containing Sceletium A4 and tortuosamine.

In contrast to what most people think, mesembrine, the alkaloid first isolated and named is not the dominant constituent of the plant. In the fermented plant material the level of mesembrenone is usually higher than the level of mesembrine.

Variation in alkaloid distribution

However, there’s no consensus about the exact alkaloid distribution in kanna. This has two reasons. First the amount of alkaloids varies between different batches of kanna and substantially alters by preparing the fresh plant material into ‘kougoed’. Factors like season, geography, growing conditions and age further influence the alkaloid distribution in the plants.

Second, there’s no consensus about the exact categorisation of the Sceletium species, therefore different alkaloid descriptions encompass different species. The Dictionary of Natural Products (2011), for example, lists 31 alkaloids from five sources of Sceletium.

Tryptamines in Sceletium tortuosum?

Mesembrenone, mesembrine and mesembrenol are considered the main alkaloids present in Sceletium tortuosum. Other alkaloids often named in the literature are mesembranol, tortuosamine, mesembrane, Sceletium A4, chennaine, 4’-O-demethylmesembranol, sceletone, joubertiamine and hordenine.

Ethnobotanist Rätsch believes it’s possible that tryptamines occur in the Sceletium tortuosum, although this was never demonstrated. Methyltryptamine (MMT) and N,N-DMT have been detected in a Delosperma species, which is a close relative from the Aizoaceae family.

Sample testing

Roscher et al (2012) compared alkaloid levels of two samples of self-fermented Sceletium tortuosum with two commercially available kanna powders and a sample of self-fermented Sceletium Joubertii. They found roughly the same alkaloids in all Sceletium tortuosum products: mesembrine, 4’-O-demethylmesembranol, mesembranol and its derivatives, and mesembrenone and its derivatives.

However, the quantities largely differed between the samples: mesembrine was dominant in one of the fermented Sceletium tortuosum plants, but not in the other. Likewise, in one of the kanna powders mesembrine and mesembrenone were dominant, whereas their levels were relatively low in the second kanna powder. Additionally, in contrast to the first kanna powder, the second sample did contain 4’-O-demethylmesembranol. Mesembrenone was not found in the Sceletium joubertii, which did contain the other three alkaloids.

Fermentation and oxalic acid in kanna

Sceletium tortuosum usually contains about 1-1.5% total alkaloids. According to Gericke and Viljoen (2008) the highest values noted in raw plant material of Sceletium are around 2% of the dry weight.

The fermentation process is believed to increase the amount of alkaloids in the plant material and reduces the levels of potential harmful oxalates. Smith et al (1996) say: “We would like to suggest that the crushing process, prior to anaerobic fermentation would introduce oxalate-degrading microbes into the skin or plastic bag and so ameliorate the potential toxic effects of oxalic acid.”

Pharmacological activity of kanna

To understand kanna’s effects, scientists have studied the neurological functioning of its most prominent alkaloids. As the alkaloid composition of the plant material is quite complex and variable, kanna’s exact workings are not yet fully understood and effects may differ from time to time.

Mesembrine, mesembrenon and mesembrenol all function as serotonin reuptake inhibitors. They block the action of the serotonin transporter and thereby increase the activity of the serotonin that’s already available in the brain. The neurotransmitter serotonin is known to regulate mood, memory and learning, appetite and sleep.

The alkaloids in Sceletium tortuosum not only block 5-hydroxytryptamine (serotonin) reuptake receptors, but are also known to inhibit the enzyme Phosphodiesterase 4 (PDE4). In general PDE4 is known to regulate mood, wakefulness and precognitive functioning (including long-term memory) and PDE4 inhibitors are said to have neuroprotective, anti-anxiety, cognition-improving, anti-psychotic, antidepressant and anti-inflammatory effects.

Blocking more than one receptor

Harvey et al (2011) tested the standardized (and patented) Sceletium extract Zembrin® on no less than 77 receptor and ion channel bindings sites. The extract, designed to contain high levels of mesembrenone, mesembrenol and mesembrine, did not affect most of these binding sites, but was found to strongly inhibit the GABA receptors, 5-HT transporter, delta-2-opioid receptor, mu-opioid receptor and cholecystokinin-1 receptor. The extract further blocked PDE4 completely, and had a partially inhibiting effect on a range of subtypes of the Phosposidesterase enzyme.

The research team also tested the three alkaloids mesembrenol, mesembrenone and mesembrine separately. By themselves they had little effect on the GABA receptors, delta-2-opioid receptor, mu-opioid receptor and cholecystokinin-1 receptor. However, all three alkaloids were shown to block the 5-HT transporter and inhibit PDE4. Mesembrine was found to be most potent blocking the 5-HT receptor, whereas mesembrenone was most potent affecting PDE4.