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Sceletium
Sceletium tortuosum
Mood enhancement and stress relief by San and Khoikhoi peoples
Sceletium contains alkaloids, primarily mesembrine and mesembrenone, that act as serotonin reuptake inhibitors. Mesembrenone also functions as a PDE4 inhibitor, which may enhance its anxiolytic effects. These mechanisms increase serotonin availability in the synaptic cleft, potentially explaining the plant's traditional mood-enhancing and anxiety-relieving properties. Evidence for these mechanisms is rated Level C, based on laboratory and animal studies rather than extensive human trials.
Can I take Sceletium with antidepressants or SSRIs?
No, Sceletium should not be combined with antidepressants or SSRIs. Because Sceletium inhibits serotonin reuptake, combining it with SSRIs or other serotonergic medications significantly increases the risk of serotonin syndrome—a potentially life-threatening condition causing agitation, confusion, rapid heart rate, high blood pressure, and muscle rigidity. This is considered a serious drug interaction. Always consult a healthcare provider before combining Sceletium with any prescription medications.
What is the recommended dosage for Sceletium?
The typical adult dosage is 25–50 mg of standardized extract daily. Traditionally, the San and Khoikhoi peoples chewed fresh plant material, but standardized extracts provide more consistent alkaloid content. Due to limited clinical evidence (Level C), individuals should start at the lower dose and assess tolerance. Consult a qualified healthcare practitioner for personalized dosing, particularly if you have underlying health conditions or take other medications.
Is Sceletium safe during pregnancy or breastfeeding?
No, Sceletium is considered unsafe during pregnancy and breastfeeding. The plant's serotonergic activity and alkaloid content may pose risks to fetal development and infant health through breast milk. There is insufficient safety data to support use during pregnancy or lactation. Pregnant or breastfeeding individuals should avoid Sceletium entirely and consult a healthcare provider for safer alternatives for mood support.
What is Sceletium used for traditionally?
Sceletium has been used for thousands of years by the San and Khoikhoi peoples of South Africa for mood enhancement, anxiety relief, and hunger and thirst suppression during long journeys. It holds sacred significance in Khoisan tradition. Modern interest focuses on potential applications for anxiety and depression, though clinical evidence remains limited (Level C). More rigorous human studies are needed to confirm traditional uses.
PubMed-compiled information sheet
This sheet was compiled from PubMed (NIH) abstracts using AI assistance. Every factual claim is cited to a real PubMed article (see the source list). It has not yet been human-reviewed — confirm with a healthcare provider before use.
Compiled from 30 PubMed articles · model: gemma4:31b
Summary
Sceletium tortuosum, commonly known as kanna or kougoed, is a South African medicinal plant used to promote well-being by relieving stress and improving mood [PMID:33924742, PMID:34333104].
Background
Sceletium tortuosum (L.) N.E.Br. is a succulent forb endemic to South Africa [PMID:34333104, PMID:34758918]. It has been used for millennia by the indigenous San and Khoikhoi (Khoisan) peoples [PMID:33924742, PMID:18761074, PMID:38576783].
Traditional uses
Traditionally, the plant was masticated or smoked to relieve toothache, abdominal pain, and to serve as a mood-elevator, analgesic, hypnotic, anxiolytic, thirst and hunger suppressant [PMID:34333104, PMID:34758918]. It was also used for healing, social, and spiritual purposes [PMID:33924742, PMID:18761074].
Active compounds
The primary active constituents are mesembrine-type alkaloids, including mesembrine, mesembrenone, mesembrenol, and mesembranol [PMID:34333104, PMID:35134486]. Hordenine is also identified as a characteristic biomarker [PMID:34750996].
Mechanism of action
Mesembrine acts as a potent inhibitor of the serotonin transporter (SERT) [PMID:31299396, PMID:35134486]. Other reported mechanisms include phosphodiesterase 4 (PDE4) inhibition, monoamine regulation, and antioxidant and anti-inflammatory properties [PMID:40643548]. Some sub-fractions may inhibit acetylcholinesterase (AChE), monoamine oxidase type B (MAO-B), and N-methyl-D-aspartic acid receptor (NMDAR) [PMID:36006974].
Clinical evidence
Evidence BAnxiety (Healthy Volunteers)
A single 25 mg dose of Zembrin® significantly reduced subjective experiences of anxiety and physiological stress indicators (heart rate and galvanic skin response) during a simulated public speaking task [PMID:32761980].
Evidence DDepression and Anxiety (Animal Models)
In rat models, Sceletium tortuosum fractions showed antidepressant properties, though some produced ataxia [PMID:24930358]. Zembrin® and mesembrine reversed anhedonia and anxiety in male rats subjected to chronic mild stress [PMID:40643548].
Evidence DAnxiety (Chick Model)
Alkaloid-enriched fractions at 75 and 100mg/kg decreased distress vocalizations during the anxiety phase [PMID:27553978].
Safety & adverse effects
A 14-day and 90-day repeated oral toxicity study in rats was conducted to assess safety [PMID:25301237]. In rodent models, some fractions associated with antidepressant activity also produced ataxia [PMID:24930358].
Drug interactions
Historical reports indicate a synergism and potentiation when used with smoked Cannabis [PMID:8691846].
Evidence summary
The evidence consists primarily of review articles, in vitro studies, and animal models (rats, chicks, zebrafish), with limited human clinical data from small-scale randomized controlled trials on healthy volunteers.
PubMed sources
1.PMID: 33924742 (2021) — A Chewable Cure "Kanna": Biological and Pharmaceutical Properties of Sceletium tortuosum. · Molecules (Basel, Switzerland)
2.PMID: 34333104 (2021) — Sceletium tortuosum: A review on its phytochemistry, pharmacokinetics, biological and clinical activities. · Journal of ethnopharmacology
3.PMID: 27939420 (2017) — Mesembrine alkaloids: Review of their occurrence, chemistry, and pharmacology. · Journal of ethnopharmacology
4.PMID: 24930358 (2014) — Effects of Sceletium tortuosum in rats. · Journal of ethnopharmacology
No direct government monograph is available for this herb. The content below is AI-generated and has not been verified against an authoritative government source. Use the search links to check official sources before relying on this information.
PMID: 8691846 (1996) — Psychoactive constituents of the genus Sceletium N.E.Br. and other Mesembryanthemaceae: a review. · Journal of ethnopharmacology
9.PMID: 40374049 (2025) — Differential impact of extracts from distinct Sceletium tortuosum chemotypes on central neurotransmitter concentrations in C57BL/6 mice. · Journal of ethnopharmacology
10.PMID: 34758918 (2022) — Sceletium tortuosum: A review on its phytochemistry, pharmacokinetics, biological, pre-clinical and clinical activities. · Journal of ethnopharmacology
11.PMID: 32761980 (2020) — Sceletium tortuosum (Zembrin® ) ameliorates experimentally induced anxiety in healthy volunteers. · Human psychopharmacology
12.PMID: 29253615 (2018) — Immunomodulatory effects of Sceletium tortuosum (Trimesemine™) elucidated in vitro: Implications for chronic disease. · Journal of ethnopharmacology
13.PMID: 20816940 (2011) — The effects of Sceletium tortuosum in an in vivo model of psychological stress. · Journal of ethnopharmacology
14.PMID: 40643548 (2025) — Neuro-Inflammatory and Behavioral Changes Are Selectively Reversed by Sceletium tortuosum (Zembrin®) and Mesembrine in Male Rats Subjected to Unpredictable Chronic Mild Stress. · Cells
15.PMID: 29520661 (2018) — Sceletium tortuosum may delay chronic disease progression via alkaloid-dependent antioxidant or anti-inflammatory action. · Journal of physiology and biochemistry
16.PMID: 25240931 (2015) — GC-MS, LC-MS(n), LC-high resolution-MS(n), and NMR studies on the metabolism and toxicological detection of mesembrine and mesembrenone, the main alkaloids of the legal high "Kanna" isolated from Sceletium tortuosum. · Analytical and bioanalytical chemistry
17.PMID: 35134486 (2022) — Mesembryanthemum tortuosum L. alkaloids modify anxiety-like behaviour in a zebrafish model. · Journal of ethnopharmacology
18.PMID: 27553978 (2016) — The effects of Sceletium tortuosum (L.) N.E. Br. extract fraction in the chick anxiety-depression model. · Journal of ethnopharmacology
19.PMID: 33536817 (2021) — First Report: Diversity of Endophytic fungi Possessing Antifungal Activity Isolated from Native Kougoed (Sceletium tortuosum L.). · Mycobiology
20.PMID: 34750996 (2022) — Quantification of hordenine in a complex plant matrix by direct analysis in real time-high-resolution mass spectrometry: Application to the "plant of concern" Sceletium tortuosum. · Drug testing and analysis
21.PMID: 34454055 (2022) — An acute dose-ranging evaluation of the antidepressant properties of Sceletium tortuosum (Zembrin®) versus escitalopram in the Flinders Sensitive Line rat. · Journal of ethnopharmacology
22.PMID: 23441963 (2013) — A randomized, double-blind, parallel-group, placebo-controlled trial of Extract Sceletium tortuosum (Zembrin) in healthy adults. · Journal of alternative and complementary medicine (New York, N.Y.)
23.PMID: 33712901 (2021) — Formulation of Medicated Chewing Gum Containing Sceletium tortuosum and Process Optimization Utilizing the SeDeM Diagram Expert System. · AAPS PharmSciTech
24.PMID: 26608705 (2016) — Electropharmacogram of Sceletium tortuosum extract based on spectral local field power in conscious freely moving rats. · Journal of ethnopharmacology
25.PMID: 23592330 (2013) — A novel approach in herbal quality control using hyperspectral imaging: discriminating between Sceletium tortuosum and Sceletium crassicaule. · Phytochemical analysis : PCA
26.PMID: 26821203 (2016) — Direct analysis in real time high resolution mass spectrometry as a tool for rapid characterization of mind-altering plant materials and revelation of supplement adulteration--The case of Kanna. · Forensic science international
27.PMID: 25301237 (2014) — A toxicological safety assessment of a standardized extract of Sceletium tortuosum (Zembrin®) in rats. · Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
29.PMID: 38576783 (2024) — Skeletons in the closet? Using a bibliometric lens to visualise phytochemical and pharmacological activities linked to Sceletium, a mood enhancer. · Frontiers in plant science
30.PMID: 36006974 (2022) — A network pharmacology-based approach to explore the therapeutic potential of Sceletium tortuosum in the treatment of neurodegenerative disorders. · PloS one