Examining The Key Psychoactive Alkaloids Responsible for Kanna Effects

• Understanding Kanna
• Kanna’s Key Psychoactive Alkaloids
• Mesembrine Chemical Profile & Biosynthesis
• What Does Mesembrine Do in the Body?
• Mesembrine Concentration in Kanna Plants
• Kanna Extracts & Mesembrine Dosage
• Why Kanna Testing Matters
• Bottom Line

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South African communities have ingested kanna plants for centuries to help with mood, cognition, anxiety, and stress. This practice makes sense, considering kanna’s key active ingredient is even more effective at altering serotonin levels than the well-known antidepressant, Prozac. Mesembrine is kanna’s strongest psychoactive alkaloid. However, the plant contains up to nine alkaloids responsible for its mood-boosting benefits. 

This article investigates kanna’s key alkaloids, spotlighting mesembrine effects, active dosages, chemical profiles, and lab testing. 

Understanding Kanna

Kanna plants in the Sceletium genus comprise several species known for their psychoactive properties. These species, used traditionally by indigenous groups in southern Africa, served various purposes, from mood elevation to appetite suppression. South Africans traditionally reaped the benefits by chewing or fermenting the leaves. 

Today, the commercial kanna extract Zembrin® exemplifies the modern therapeutic application of the plant for mood, stress, and focus. 

Kanna’s Key Psychoactive Alkaloids

Kanna contains up to nine alkaloids responsible for its psychoactive properties. It primarily exerts narcotic-anxiolytic (anxiety-reducing) effects without causing hallucinations or a traditional sense of euphoria.

Most research focuses on four kanna alkaloids: Mesembrine, mesembrenol, mesembrenone, and mesembranol. 

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Mesembrine: Mesembrine is kanna’s key active compound. This alkaloid is the most effective in blocking the reabsorption of serotonin, a neurotransmitter that contributes to feelings of well-being and happiness. Research suggests it can also increase serotonin release in the brain. Mesembrine’s ability to affect serotonin levels with high potency significantly contributes to kanna's mood-enhancing effects. Mesembrine also works by inhibiting the PDE4 enzyme, which is involved in cognition, mood, and behavior.

Despite being the key compound, mesembrine is not always the dominant kanna alkaloid in terms of concentration. Thus, kanna’s psychoactive effects result from the combined action of all its alkaloids, which varies based on the strain.

• ‍Mesembrenone: This alkaloid is present in higher concentrations in some strains of kanna.  Like mesembrine, mesembrenone is a selective serotonin reuptake inhibitor. But it acts with less strength than mesembrine.  Mesembrenone’s strength is that it is more effective at inhibiting the PDE4B enzyme. This action is essential because PDE4B plays a role in managing mood and mental functions. By inhibiting this enzyme, mesembrenone helps enhance mood and improve cognitive abilities.‍
• Mesembrenol: Mesembrenol also inhibits the PDE4B enzyme but is less potent than mesembrine and mesembrenone. Still, mesembrenol contributes to kanna's overall effects, adding to its complexity as a psychoactive plant.‍
• Mesembranol: Research on mesembranol is scant compared to mesembrine, mesembrenol, and mesembrenone. But mesembranol is another kanna alkaloid that helps manage mood and anxiety through action as a serotonin reuptake inhibitor. Additionally, some evidence suggests it may also play a role in inhibiting the PDE4 enzyme. ‍
• Cannabis Synergy: One study found that a kanna extract interacted with the cannabinoid receptor 1 (CB-1), responsible for cannabis’ psychoactive effects. This suggests that kanna alkaloids could potentially enhance or alter the effects of cannabis, indicating a synergy between the two. Additionally, the extract inhibited acetylcholinesterase, an enzyme linked to memory and learning.

Mesembrine Chemical Profile & Biosynthesis

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Mesembrine in kanna plants exhibits a distinct chemical profile characterized by its chiral aryloctahydroindole skeleton. In simpler terms, 'chiral' refers to a molecular property where two forms of a molecule are mirror images, like left and right hands. This specific structure is crucial for mesembrine's interaction with biological systems, particularly in affecting brain chemistry.

The compound's molecular formula, C17H23NO3, reveals its carbon, hydrogen, nitrogen, and oxygen atoms composition. A quaternary stereogenic center within this formula is a crucial feature. This center, difficult to replicate synthetically, is a point in the molecule where carbon is bonded to four other distinct groups, making the compound's synthesis in the lab a significant challenge.

Mesembrine biosynthesis is a complex process. It involves the integration of amino acids tyrosine and phenylalanine through intricate biochemical pathways. These pathways form the compound's octahydroindole core, a cyclohexanone ring fused to a saturated pyrrolidine, crucial for its pharmacological activity.

What Does Mesembrine Do in the Body? 

Central to mesembrine's intrigue is its potent impact on the central nervous system. It's an effective inhibitor of the serotonin transporter (SERT), even more so than fluoxetine (Prozac), a commonly prescribed antidepressant. This means that mesembrine could potentially be more potent in increasing serotonin levels in the brain, offering a more pronounced therapeutic effect in enhancing mood and cognitive functions.

Studies suggest that mesembrine might act as a:

• Mild antidepressant
• Anxiolytic
• Mood booster
• Stress reliever
• Sleep enhancer

Its potential as an anti-addiction agent is also under exploration.

Mesembrine Concentration in Kanna Plants

Mesembrine occurs in at least three kanna species at varying concentrations depending on the strain and growth conditions.

1. Sceletium tortuosum
2. S. strictrum
3. S. expansum

Generally speaking, kanna roots contain about 0.3% mesembrine, and the leaves, stems, and flowers contain about 0.86%. 

Kanna Extracts & Mesembrine Dosage

Traditional use suggests daily kanna doses between 500 and 1,500 mg could be safe. But these numbers far exceed clinical guidelines. 

Clinical studies suggest 25-50 mg kanna extract daily, standardized to 0.4% total alkaloids (100-200 micrograms), could be effective for anxiety and depression.  

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Clinical Studies

A 2021 investigative report aggregated kanna dosage recommendations from various clinical studies on Sceletium for anxiety, depression, and cognitive health. 

• fMRI Study on Anxiety: An experiment using an fMRI, a brain imaging technique, found that a single 25 mg dose of Zembrin® (which has 100 micrograms of mesembrine alkaloids) made the amygdala, a brain part that reacts to fear, less responsive. 
• Older Adults' Cognitive Function: For older adults, taking 25 mg of Zembrin® every day significantly improved their ability to think and adapt to new situations. Additionally, these adults also experienced better mood and sleep.
• Brain Electrical Activity in Adults: Studies showed that taking 25 mg or 50 mg doses of pharmaceutical kanna extract positively influenced brain activity, especially when adults faced tasks requiring thinking or dealing with emotions.
• Cognitive Function and Anxiety in Older Adults: When older adults took 25 mg or 50 mg of Zembrin® daily for six weeks, their thinking abilities improved, and they felt less anxious.

Clinical studies capped the daily doses at 50 mg. However, clinical case reports have shown success at 75 to 100mg (300-400 micrograms) of total alkaloids. Additionally, a toxicology assessment found that a 150-pound person could safely consume 420 mg of kanna extract a day. 

Why Kanna Testing Matters

Kanna lab testing is essential to quantify the plan or extract’s main psychoactive alkaloids, including mesembrenone, mesembrenol, mesembranol, and mesembrine). High-pressure liquid chromatography (HPLC) analysis against validated analytical references produces precise potency concentrations, which is critical to understanding the formula’s therapeutic potential. 

Kanna testing should also include safety and purity panels to ensure the product is contaminant-free. 

Brands that test kanna with third-party laboratories can publish the reports, known as Certificates of Analysis (COAs), for consumers to see, inspiring trust and loyalty. 

Bottom Line 

ACS Laboratory is acquiring validated analytical references for kanna and looks forward to supporting brands in this market soon. Contact ACS today to ask about our upcoming kanna testing program or to learn about our hemp, cannabis, mushroom, and kratom panels. 

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