Introduction
In today’s fast-paced, high-pressure environment, chronic stress has become a widespread issue impacting mental, emotional, and physical health. While pharmaceuticals are commonly prescribed for anxiety and stress-related conditions, many individuals are now seeking natural, research-backed alternatives. Among the promising candidates is Sceletium tortuosum, more widely known as Kanna.
Kanna is a succulent plant indigenous to South Africa and traditionally used by the Khoisan people for its calming and mood-enhancing properties. Historically, Kanna was chewed, brewed as tea, or fermented to help with social bonding, endurance during hunting, and emotional stability during hardship (1).
Modern pharmacological research has now begun to validate these traditional applications. Studies indicate that Kanna’s bioactive alkaloids, particularly mesembrine and mesembrenone, may influence serotonin pathways and stress hormone regulation in the brain. This article examines the current body of scientific literature supporting Kanna’s effectiveness for stress relief and highlights how this plant bridges traditional ethnobotany with evidence-based wellness practices.
Understanding Kanna’s Active Compounds and Stress-Relief Potential
The biological effects of Kanna stem from a group of naturally occurring alkaloids, including mesembrine, mesembrenone, mesembrenol, and tortuosamine. These compounds interact with key biochemical pathways in the central nervous system, particularly those related to serotonin modulation and hormonal stress responses.
Modulating the Serotonin System
Among Kanna’s alkaloids, mesembrine is perhaps the most well-studied. It functions as a selective serotonin reuptake inhibitor (SSRI), which means it prevents the reabsorption of serotonin in the brain. As a result, serotonin levels remain elevated for longer periods, contributing to stabilized mood and enhanced emotional resilience (2).
While pharmaceutical SSRIs such as fluoxetine (Prozac) also work through this mechanism, they often come with side effects such as fatigue, nausea, or emotional blunting. In contrast, early clinical trials suggest that Kanna’s serotonin-enhancing effects have shown a favorable tolerability profile in early studies, with no significant adverse effects reported under controlled conditions when used at appropriate dosages (3).
Regulating the Hypothalamic-Pituitary-Adrenal (HPA) Axis
Another way Kanna influences stress physiology is through its modulation of the HPA axis. This system is responsible for releasing stress hormones such as cortisol and adrenaline. In times of prolonged stress, chronic overactivation of the HPA axis can lead to health complications such as fatigue, anxiety, high blood pressure, and weakened immune function.
A 2013 randomized controlled trial found that daily supplementation with Zembrin®, a standardized Kanna extract, helped reduce subjective stress levels while also reducing cortisol responses to emotional stressors (5). Participants also showed reduced activity in the amygdala, a brain region closely linked to fear, anxiety, and emotional regulation.
Electrophysiological Changes in the Brain
In addition to serotonin and hormonal pathways, researchers have explored how Kanna affects brainwave activity. An electropharmacological study in conscious rats found that Kanna extract significantly altered alpha2 and beta1a wave activity, brainwaves associated with attention, stress response, and arousal. These changes suggest that Kanna may also influence norepinephrine and glutamate pathways, which are integral to emotional resilience and behavioral responses to stress (4).
Preclinical Evidence: Animal Studies on Stress Response
Before clinical trials are conducted in humans, preclinical studies help evaluate the safety and biological effects of herbal compounds. Kanna has been studied in multiple in vivo animal models, particularly focusing on how it affects behavioral and hormonal markers of stress.
Reducing Corticosterone in Rodent Models
One of the most cited studies on Kanna’s anti-stress properties involved Wistar rats subjected to stress-inducing conditions. The animals were administered Zembrin® over a 17-day period. Results showed a significant reduction in corticosterone, the rodent equivalent of human cortisol, indicating a lowered stress response at the physiological level (1).
Corticosterone is widely used in stress research as a biomarker for HPA axis activation. The reduction in this hormone following Kanna supplementation highlights the herb’s potential role in lowering chronic stress reactivity.
Behavioral Adaptations in Stress Models
Beyond hormone levels, researchers observed improvements in stress-related behaviors. Rats receiving Kanna displayed fewer anxiety-related movements in open field tests and light/dark transition tests, both common assessments used to quantify anxiety-like behavior in animal models. These results mirror traditional uses of Kanna as a calming aid and provide biological validation for its anxiolytic potential.
Clinical Trials: Human Evidence for Stress Relief
While preclinical studies offer promising insights, human trials provide the most compelling evidence for Kanna’s real-world application. Several clinical studies have evaluated the safety, tolerability, and stress-reducing effects of Kanna extracts, particularly Zembrin®, which is standardized for consistent alkaloid levels.
Amygdala Deactivation and Emotional Regulation
In a placebo-controlled fMRI study, participants were given either Zembrin® or a placebo and subjected to emotionally charged visual stimuli. Researchers found that individuals who received Zembrin® exhibited significantly lower amygdala activation compared to the placebo group. Reduced amygdala activity is linked to decreased emotional reactivity and improved stress tolerance (3).
This was one of the first studies to demonstrate, using imaging, that Kanna can modulate specific brain structures involved in the stress response.
Effects on Self-Reported Stress and Well-Being
A follow-up randomized, double-blind trial tracked healthy participants over four weeks of daily Zembrin® supplementation. Results indicated improved scores on mood and stress resilience assessments, with many participants reporting:
- Improved ability to stay calm under pressure
- Reduced fatigue and emotional exhaustion
- Better overall mood and positivity (5)
Participants also noted that Kanna’s calming effects did not come with sedation or cognitive dulling, which are often concerns with pharmaceutical alternatives.
Transitioning to Clinical Applications
The promising findings from preclinical animal studies have paved the way for clinical trials investigating Kanna’s effects in humans. These trials assess how the plant’s alkaloids interact with neurochemical systems under stress, focusing on both psychological and physiological outcomes.
Clinical Trials on Kanna’s Anti-Stress Properties
Human clinical studies have offered compelling evidence that Kanna helps modulate emotional responses and stress markers without impairing cognition. These findings validate its traditional uses and pharmacological potential.
Zembrin® and Amygdala Modulation
A pivotal double-blind, placebo-controlled study investigated the effects of Zembrin®, a standardized Kanna extract, using functional MRI. Participants were given a single dose and exposed to threat-related stimuli to assess amygdala reactivity. The amygdala plays a central role in emotional processing and is often hyperactive in individuals under chronic stress.
The study found that participants receiving Zembrin® had reduced amygdala activation compared to the placebo group. These effects occurred without sedation or cognitive dulling, making Kanna distinct from pharmaceutical anxiolytics that can impair alertness (3).
Participant-Reported Benefits
In trials involving daily Zembrin® supplementation over several weeks, participants reported multiple improvements relevant to stress management:
- Greater calm under pressure
- Improved mood stability
- Better sleep quality
- Reduced emotional reactivity
These outcomes suggest that Kanna was associated with reduced physiological stress markers and improvements in self-reported well-being and coping ability (5).
Long-Term Safety and Tolerability
Safety remains a top concern in any botanical intervention. In a toxicological study using animal models, even high doses of Zembrin® showed no significant adverse effects or organ toxicity. Additionally, clinical trials reported a low incidence of side effects, with no reports of dependency or withdrawal symptoms (6).
These findings strengthen the case for Kanna as a reliable option for long-term stress management, especially for individuals seeking alternatives to conventional medications.
Supporting Cognitive Function Under Stress
Chronic stress not only affects mood but also impairs cognitive function. Elevated cortisol levels and prolonged neural tension can interfere with memory, decision-making, and mental clarity. Several studies have evaluated whether Kanna can help preserve or improve cognitive function in high-stress situations.
Functional Cognitive Tests
In one study, participants took standardized cognitive assessments during and after Zembrin® administration. Those in the Kanna group demonstrated:
- Faster reaction times
- Greater task accuracy
- Improved focus and decision-making
This suggests that Kanna may buffer against the cognitive drain often caused by prolonged stress exposure (5).
Neuroprotective Mechanisms
Kanna’s cognitive benefits may stem from its ability to:
- Reduce oxidative stress in the brain
- Modulate cortisol release
- Enhance serotonin signaling, which affects both mood and executive function
These mechanisms may offer a dual layer of support that helps maintain brain function while promoting emotional stability.
Practical Considerations for Using Kanna
Understanding the practical aspects of Kanna usage is essential for consumers looking to incorporate it into a stress-management routine.
Choosing the Right Product
Not all Kanna products are created equal. For clinical-grade benefits, standardized extracts like Zembrin® and KannaEase™ offer consistent concentrations of key alkaloids, particularly mesembrine and mesembrenone.
Look for:
- Third-party testing
- Certificates of analysis
- Clearly listed alkaloid content
Avoid products with vague labeling or no reference to standardization.
Recommended Forms and Dosages
Kanna is available in various forms:
- Capsules: Preferred for consistent daily use
- Powders: Suitable for tea or food integration
- Tinctures: Good for flexible dosing and rapid onset
While dosages vary by formulation, most clinical studies have used 8–25 mg of standardized extract per day. It is best to follow manufacturer recommendations and consult with a healthcare provider.
Timing and Duration
For general stress support, Kanna can be used as:
- A daily supplement for baseline mood support
- An acute aid during stressful events
Some individuals may notice subtle effects within hours, while others require 1–2 weeks of consistent use. Importantly, existing studies have not found evidence of tolerance building over time, allowing for sustained use without increasing dosage (6).
Safety and Interactions
Kanna is generally well-tolerated, but caution should be exercised when combining it with:
- SSRIs or SNRIs
- MAOIs
- Other serotonergic compounds
Due to its serotonin-modulating properties, combining it with these drugs may increase the risk of serotonin syndrome. Always consult a physician before combining Kanna with prescription medications or other herbal supplements targeting mood.
Conclusion
Kanna presents a promising, research-informed approach to stress support. Its dual-action mechanism, boosting serotonin availability and regulating cortisol, addresses both the emotional and physiological effects of stress. Unlike pharmaceutical interventions that may cause sedation or dependency, Kanna promotes a calm, clear-headed state without impairing mental function.
As the pressures of modern life continue to grow, Kanna’s potential to support emotional resilience, cognitive clarity, and hormonal balance positions it as a potentially valuable addition to natural wellness strategies. With a solid safety profile, a long history of traditional use, and growing clinical validation, Kanna stands out as a meaningful addition to holistic stress management strategies.
Sources
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- Harvey AL, Young LC, Viljoen AM, Gericke NP. Pharmacological actions of the South African medicinal and functional food plant Sceletium tortuosum and its principal alkaloids. J Ethnopharmacol. 2011;137(3):1124-9.
- Terburg D, Syal S, Rosenberger LA, Heany S, Phillips N, Gericke N, Stein DJ, van Honk J. Acute effects of Sceletium tortuosum (Zembrin), a dual 5-HT reuptake and PDE4 inhibitor, in the human amygdala and its connection to the hypothalamus. Neuropsychopharmacology. 2013;38(13):2708-16.
- Dimpfel W, Schombert L, Gericke N. Electropharmacogram of Sceletium tortuosum extract based on spectral local field power in conscious freely moving rats. J Ethnopharmacol. 2016;177:140–147.
- Nell H, Siebert M, Chellan P, Gericke N. A randomized, double-blind, parallel-group, placebo-controlled trial of extract Sceletium tortuosum (Zembrin) in healthy adults. J Altern Complement Med. 2013;19(11):898-904.
- Murbach TS, Hirka G, Szakonyine IP, Gericke N, Endres JR. A toxicological safety assessment of a standardized extract of Sceletium tortuosum (Zembrin) in rats. Food Chem Toxicol. 2014;74:190-199.
