top of page

The Phytochemistry & Pharmacology of Sceletium Tortuosum

​Sceletium tortuosum, traditionally known as Kanna, is a succulent native to South Africa with a documented history of use spanning over three centuries. Beyond its traditional roots, modern pharmacology has identified a complex alkaloid matrix that makes Kanna one of the most effective natural adaptogens for neurological health.

soiltohand_edited.jpg

1. Primary Mechanism of Action: VMAT-2 & SRA

Unlike synthetic compounds that simply flood the brain with serotonin, Sceletium works through a sophisticated dual-action mechanism:

​

PDE4 Inhibition (Phosphodiesterase 4)

Sceletium is a potent inhibitor of the PDE4 enzyme. By inhibiting PDE4, the plant increases levels of cyclic Adenosine Monophosphate (cAMP).

  • The Result: Enhanced neuroplasticity, improved memory consolidation, and a significant reduction in neuro-inflammation.
     

Serotonin Reuptake Inhibition (SRI)

The alkaloids act as a natural Selective Serotonin Reuptake Inhibitor (SSRI) by binding to the SERT transporter.

  • The Result: A sustained "pool" of available serotonin in the synaptic cleft, promoting emotional stability and a "buffered" response to external stressors.
     

2. The Alkaloid Matrix & The Entourage Effect

Our extraction process prioritizes the four primary alkaloids that define the Sceletium experience.

  • Mesembrine: The primary "uplifter." It is a potent SRI and is responsible for the initial onset of focus and euphoria.

  • Mesembrenone: The "balancer." It shows high selectivity for PDE4 inhibition, providing the cognitive "edge" and neuroprotective qualities.

  • Mesembrenol & Tortuosamine: These secondary alkaloids act as GABA-A modulators, providing the "grounding" or "anxiolytic" (anti-anxiety) tail-end of the experience.
     

3. Extraction & Fermentation: The Oxalate Issue

In its raw state, Sceletium contains high levels of Oxalic Acid, which can be taxing on the kidneys and cause a "scratchy" sensation in the throat.

  1. Traditional Fermentation: We crush the plant material and seal it in an anaerobic environment. This triggers a breakdown of oxalates and transforms some Mesembrine into the more stable Mesembrenone.

  2. Standardization: Our extracts are processed to ensure a consistent alkaloid percentage, removing the variability found in wild-harvested "kruid" (herb).
     

Mechanism of Action

Sceletium tortuosum, commonly known as Kanna, operates through a rare "dual-action" pharmacological profile. Primarily, it acts as a selective serotonin reuptake inhibitor (SRI), increasing the availability of serotonin in the synaptic cleft. Simultaneously, it functions as a phosphodiesterase 4 (PDE4) inhibitor. By blocking the PDE4 enzyme, the plant prevents the breakdown of cyclic adenosine monophosphate (cAMP), a secondary messenger critical for regulating emotional response and cognitive function. This synergy allows for an immediate reduction in anxiety (anxiolytic) without the typical sedative effects of other botanical relaxants.

​

Seasonal Variance in Alkaloid Expression

The chemical potency of Sceletium is not static; it fluctuates significantly according to the plant's phenological stages and environmental stressors. Research into the concentration of $\Delta^7$-mesembrenone reveals that the plant reaches its peak chemical expression during the summer months, yielding a high of $1.31\%$ in January. This coincides with the plant’s flowering period and maximum heat exposure in its native South African habitat. As the seasons transition into autumn, there is a marked decline in alkaloid density, dropping to $0.81\%$ by April, eventually reaching a dormant-season low of $0.18\%$ in July. By the time spring returns in October, the plant begins to regenerate its chemical defenses, with levels climbing back to approximately $0.44\%$ as the growth cycle restarts.
 

5. Usage Protocol & Bioavailability

The Sublingual Advantage

By applying a 25-50 mg dose sublingually, the alkaloids enter the sublingual vein directly, bypassing "First-Pass Metabolism" in the liver. Crossing the blood-brain barrier occurs within 5–15 minutes.
 

The 48-Hour Reset (Receptor Homeostasis)

The recommendation to wait 48 hours between doses is based on Receptor Downregulation.

  • The Clearing Phase: It takes approximately 36 to 48 hours for the alkaloid metabolites to clear the VMAT-2 transporters.

  • The Result: Observing the 48-hour reset prevents tolerance, keeping a 25-50 mg dose effective indefinitely.
     

6. Contraindications & Safety (Critical)

Because Kanna acts on the Serotonin system, it must not be combined with certain substances:

  • SSRIs/SNRIs: Combining Kanna with prescription antidepressants (like Prozac, Zoloft, or Lexapro) can lead to Serotonin Syndrome, a potentially dangerous condition.

  • MAOIs: Do not use in conjunction with Monoamine Oxidase Inhibitors (including some herbal MAOIs like Syrian Rue or Ayahuasca).

  • Alcohol: While not life-threatening, Kanna can significantly potentiate the effects of alcohol, leading to unexpected sedation or dizziness.

​

Primary Alkaloids

  • Mesembrine: The most prominent alkaloid, responsible for the potent SRI activity and the initial "uplifting" sensation.

  • Mesembrenone: Acts as a balanced SRI and PDE4 inhibitor, often associated with the "calming" or stabilizing tail-end of the experience.

  • Tortuosamine: A secondary alkaloid that may influence the dopaminergic system, though research is ongoing.
     

Clinical Research References

  • Gericke, N., & Viljoen, A. M. (2008): Sceletium tortuosum: A review of ethno-botany, and chemistry.

  • Terburg, D., et al. (2013): Acute effects of Sceletium tortuosum (Zembrin) on amygdala reactivity to threat.

  • Harvey, B. H., et al. (2011): Evaluating the anxiolytic-like effect of Sceletium tortuosum.

bottom of page