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Sceletium Tortuosum

Scientific Name(s): Mesembryanthemum tortuosum, Sceletium tortuosum (L.) N.E. Br.
Common Name(s): Channa, Kanna, Kougoed

Medically reviewed by Drugs.com. Last updated on Oct 22, 2024.

Clinical Overview

Use

S. tortuosum has traditionally been used for mood-altering purposes, including for relief of anxiety and depression. Limited clinical trials have been conducted evaluating potential anxiolytic, neurocognitive, and antidepressant activities of S. tortuosum. However, clinical data are lacking to recommend use for any indication.

Dosing

Published clinical evidence is lacking to provide dosing recommendations. S. tortuosum is typically available as a tincture, tablet, or capsule in unit doses of 50 to 200 mg of the dried, milled herbal material.

Contraindications

Contraindications have not been identified.

Pregnancy/Lactation

Avoid use. Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

None well documented.

Adverse Reactions

Data are limited regarding adverse reactions associated with S. tortuosum use. Treatment-emergent adverse effects, typically mild to moderate in nature, have been reported in small clinical trials.

Toxicology

No data.

Scientific Family

Botany

S. tortuosum is a perennial decumbent or climbing succulent plant indigenous to South Africa.(Gericke 2008, Harvey 2011b) It has white to pale yellow or pale pink sessile flowers, usually 20 to 30 mm in diameter and with 4 to 5 sepals. The plant's recurved leaves have distinctive idioblasts, or water cells, and the stems become woody with age.(Gerbaulet 2002, Gericke 2008, Smith 1996) Kanna should not be confused with the ganna plant (Salsola dealata Botsch.).

History

Dutch explorers first documented the use of S. tortuosum in 1685. Its name is derived from the Latin word sceletus (meaning skeleton) because the prominent veins on the dried leaves give the plant a skeletal appearance.(Gericke 2008) The common names kanna and kougoed are derived from the Khoi and Afrikaans words, respectively, for "chewed," which refers to the traditional method of S. tortuosum administration.(Smith 1996)

S. tortuosum has a long history of use in South Africa and is one of the region's most coveted botanical assets. Traditional preparation involves crushing the plant material, placing it in a bag to ferment, then drying it in the sun.(Smith 1996) The dried plant material can be chewed, smoked, or made into powder and used as snuff.(Mitchell 2004, Nielsen 2004) The plant material has also been prepared as a tincture or tea, or eaten raw.(Smith 1996) S. tortuosum has historically been used for spiritual and social purposes by San hunter-gatherers and Khoi pastoralists.(Gericke 2008) S. tortuosum was widely traded and highly valued by the late 18th century, especially in the Eastern Cape of South Africa, and was sometimes used with cannabis, a combination that enhanced the intoxicating effect of cannabis.(Mitchell 2004) Several tribes in Africa have traditionally used S. tortuosum to elevate mood, relieve anxiety and depression, regulate sleep, and quench thirst and hunger, as well as for its masticatory, analgesic, narcotic, sedative, antispasmodic, and GI effects. S. tortuosum has been used as a sedative in the form of a tea, decoction, or tincture. Another traditional use is as a local anesthetic and analgesic for extracting teeth from the lower jaw.(Gericke 2008, Smith 1996) A small amount of S. tortuosum added to 5 mL of breast milk or mixed with a small amount of sheep tail fat has been used to treat colic in infants.(Gericke 2008, Mannetti 2011, Mitchell 2004, Nielsen 2004, Setshedi 2012, Smith 2011, Stafford 2009)

S. tortuosum is widely sold in specialty herb shops and on the internet for the purpose of increasing sexual performance.(Brunetti 2020)

Chemistry

Four basic ring systems, differentiated by the shape and oxidation of the carbon ring, have been identified in S. tortuosum. The mesembrine alkaloids are the most active of these subgroups.(Jeffs 1981) Other alkaloids include mesembrone, mesembrenol, and turtuosamine. Gas chromatography–mass spectroscopy confirms that the unfermented preparation of S. tortuosum contains more alkaloids than the fermented one.(Lubbe 2010) Although data are conflicting, reports suggest that activity is only observed when S. tortuosum is fermented, not when it is dried or fresh.(Smith 1996) Fermentation causes transformation of mesembrine to delta-7 mesembrenone. As a result, the amount of mesembrine contained in the aerial parts is reduced from 1.33% before fermentation to 0.05% after fermentation. Tests on pure mesembrine hydrochloride substantiate that sunlight and aqueous conditions are required to facilitate this transformation and to obtain the active alkaloids.(Patnala 2009) This traditional fermentation removes harmful oxalates while retaining the active alkaloids.(Smith 1998) In extracts, the alkaloids are more bioavailable across the intestinal, buccal, and mucosal tissues. When S. tortuosum is chewed, the alkaloids cross the membranes more easily.(Shikanga 2012)

Mesembrine, a phenylethylamine alkaloid, was first extracted from S. tortuosum in 1898.(Smith 1998) It is the major alkaloid found in S. tortuosum, occurring at levels of 0.3% in the leaves and 0.86% in the stems. The amount of active compounds in the plant appears to vary by season and locality. Mesembrine is the major psychoactive compound in S. tortuosum(Nielsen 2004) and is a potent selective serotonin (5-HT) reuptake inhibitor (SSRI).(Gericke 2008, Harvey 2011b, Lubbe 2010, Patnala 2009, Roe 2008, Shikanga 2011, Shikanga 2012, Smith 2011, Stafford 2009) At much higher concentrations, mesembrine has demonstrated limited inhibition of noradrenaline and dopamine uptake. Mesembrine hydrochloride is an inhibitor of phosphodiesterase type 4 (PDE4) at a half maximal inhibitory concentration of 29 mcM. The selective inhibition of the PDE4 family of enzymes affects cell signaling.(Gericke 2008) The total synthesis of (±)-mesembrine has been reported.(Jeffs 1981) Mesembrine alkaloids have been synthesized in a manner similar to that of Amaryllidaceae alkaloids.(Roe 2008, Shamma 1968)

The alkaloids in S. tortuosum may block cannabinoid type 1 (CB1) receptors, which are key in inhibiting adenylate cyclase activity, regulating ion channel activities, and activating the mitogen-activated protein kinase cascade. CB1 receptors are found in close proximity to 5-HT transporters and mediate their release. In a CB1 binding assay, combinations of the fermented alkaloid extract and the synergistic activity of the combined alkaloids resulted in greater activity. In an assay of a methanol extract of S. tortuosum, both fermented and unfermented alkaloids had a similar ability to inhibit acetylcholinesterase, a cholinesterase enzyme that terminates nerve impulse transmission in the CNS, demonstrating greater activity than mesembrine alone and suggesting that other alkaloids contribute to the acetylcholinesterase-inhibiting ability of S. tortuosum.(Lubbe 2010)

Mesembrine and other Sceletium alkaloids (mesembrone, mesembrenol, and turtuosamine) were patented in 1997.(Stafford 2009)

Uses and Pharmacology

S. tortuosum reportedly acts as an SSRI, a PDE4 inhibitor, an acetylcholinesterase inhibitor, a CB1 receptor blocker, and a CYP17A1 inhibitor. It has been suggested that the plant's SSRI activity is secondary to its monoamine-releasing activity.(Coetzee 2016) SSRIs are important in the therapeutic management of depression.(Gericke 2008, Harvey 2011a, Harvey 2011b, Mitchell 2004, Setshedi 2012, Shikanga 2011, Stafford 2009, Swart 2016) PDE4 inhibitors are used for the treatment of inflammatory diseases, including asthma, chronic obstructive pulmonary disease, and psoriasis, as well as for the treatment of anxiety and depression.(Gericke 2008, Shikanga 2012) Evidence suggests that PDE4 inhibitors also have a crucial role in regulating cognition via the PDE4-cyclic adenosine monophosphate cascade.(Blokland 2012) Acetylcholinesterase inhibitors have been used in the treatment of Alzheimer disease, senile dementia, ataxia, myasthenia gravis, and Parkinson disease. Blockage of CB1 receptors has produced antidepressant effects, efficacy in drug addiction disorders, and cognition enhancement.(Lubbe 2010) The trimesemine extract of S. tortuosum modulates glucocorticoid, mineralocorticoid, and androgen production in human adrenocortical carcinoma cells, suggesting a potential role in the management of stress and depression.(Swart 2016) Further studies regarding S. tortuosum's effectiveness in these applications are necessary.

Antimalarial activity

In vitro data

Compounds of S. tortuosum have been evaluated for antimalarial activity.(Setshedi 2012)

Athletic performance

Clinical data

In a randomized, placebo-controlled study of 60 healthy college recreational athletes, 8-day administration of S. tortuosum extract (Zembrin) 25 mg/day led to relatively few significant improvements in performance measures. Significant improvement was noted with the extract in one of the motor responses (reaction to visual stimulus; P=0.05) and in reactive agility that required decision making (P<0.001). However, no benefit was observed for the other physical performance (ie, motor, visual, and physical reaction time) or fatigue and focus assessments. In contrast, subjective feelings of fatigue were better in the placebo group (P=0.023). The extract was well tolerated, and no adverse events were reported.(Hoffman 2020)

Cancer

In vitro data

Mesembrenone has been tested for cytotoxic effects on various cell lines. It was found to affect a human T-cell lymphoma line (Molt4 cells), but had little effect on a hepatoma cell line (HepG2) or on a mouse fibroblast line (LMTK cells).(Gericke 2008, Harvey 2011b) One study demonstrated that mesembrenone was moderately effective against cancer cells and less toxic to mouse fibroblasts than other amaryllidaceous alkaloids.(Smith 1996) Further studies are necessary.

CNS effects

Analgesic effects

Animal data

When the S. tortuosum fraction mesembrine was administered to male Sprague-Dawley rats, analgesic properties were observed without abuse liabilities or ataxia.(Loria 2014)

Anxiety/Depression

Animal data

In a study of male Wistar rats, an extract of unfermented S. tortuosum had some positive effects on psychological stress; however, doses used in the study produced inflammatory responses suggestive of intolerance and varying degrees of T-helper cell 1 (Th1) immune suppression.(Smith 2011) Electropharmacogram has shown that the S. tortuosum commercial product Zembrin (a 2-fold concentrated product; 25 mg of Zembrin is equal to 50 mg of the dried plant mass) has dose-dependent activity as an antidepressant in adult Fischer rats.(Dimpfel 2016) In another study, S. tortuosum extract products administered to male Sprague-Dawley rats demonstrated antidepressant properties but also produced ataxia; potential for ataxia may limit the usefulness of S. tortuosum as an antidepressant unless the antidepressant activity is associated with one constituent and ataxia is associated with another.(Loria 2014) In case studies, the dry, powdered plant material had beneficial effects in cats with stress.(Gericke 2008, Harvey 2011b)

Clinical data

The acute effects of S. tortuosum extract (Zembrin 25 mg) on the human brain were examined in a double-blind, placebo-controlled, single-dose, crossover study of 16 healthy subjects using functional magnetic resonance imaging (MRI). Treatment reduced amygdala reactivity to fearful stimulus and amygdala-hypothalamus coupling, thus supporting the possibility of anxiolytic and antidepressant activities of S. tortuosum.(Terburg 2013) Results from 2 small, double-blind, randomized, placebo-controlled behavioral studies (N=20 each) were equivocal regarding the effect of S. tortuosum (Zembrin 25 mg) on induced anxiety. No effect was found on feelings of stress or memory performance during multitask tests; however, stress responses before simulated public speaking were significantly reduced.(Reay 2020)

Cognitive function

Animal and in vitro data

An electropharmacogram of Zembrin showed dose-dependent cognitive function enhancement in adult Fischer rats.(Dimpfel 2016) Studies also showed beneficial effects of S. tortuosum in dogs with clinically diagnosed dementia.(Gericke 2008, Harvey 2011b) A high-mesembrine extract of S. tortuosum demonstrated dose-dependent full neuroprotection in astrocytes via apparent anti-inflammatory actions. In contrast, a high–delta7-mesembrenone extract decreased astrocyte cell viability that appeared to be due to pro-oxidant effects observed at high doses. Both extracts exhibited mild inhibitory action on 2 neural enzymes associated with neurodegeneration, acetylcholinesterase, and tyrosinase.(Bennett 2018)

Clinical data

A 9-week pilot, randomized, placebo-controlled, crossover study evaluated the neurocognitive effects of S. tortuosum extract (Zembrin 25 mg) administered once daily for 3 weeks in 21 healthy subjects. The primary measure, CNS Vital Signs test, demonstrated improvement in 2 of 10 domains (cognitive set flexibility and executive function) with S. tortuosum compared with placebo. Both groups showed negative change in the domain of visual memory. Compared with placebo, there were no improvements in other domains for memory (verbal or composite memory) or for reaction speed and composite attention. According to the Hamilton Depression Rating Scale (HAM-D), positive changes were observed for mood and sleep. Vital signs were stable throughout the study. Adverse events occurring at a greater than 5% incidence in subjects treated with S. tortuosum extract that were not reported with placebo included weight gain (14%), increased appetite (10%), increased thirst (10%), and tiredness/fatigue (10%).(Chiu 2014)

Drug dependence

S. tortuosum has been investigated for a potential role in reducing drug dependence(Gericke 2008, Lubbe 2010, Shikanga 2011, Shikanga 2012); limited clinical data are available.

Epilepsy

Animal and in vitro data

In vivo and ex vivo animal studies suggest S. tortuosum (as the commercial product Zembrin) may have antiepileptic effects by attenuating excitability of intrahippocampal neurons in a dose-dependent manner.(Dimpfel 2018)

Quality of sleep

Clinical data

In a small randomized, double-blind, placebo-controlled, crossover study in healthy subjects (N=21), those taking S. tortuosum extract 25 mg (Zembrin) once daily for 9 weeks reported improvement in subjective quality of sleep on the sleep subscale of the HAM-D. While no subjects had a history of insomnia, data showed Zembrin had a positive effect on onset of sleep compared with placebo (P=0.049).(Chiu 2014)

Sexual performance/libido

The dual inhibitory effect of S. tortuosum alkaloids on serotonin reuptake and PDE4A has been suggested as a mechanism for potential sexual performance and libido enhancement.

Dosing

Published clinical evidence is lacking to provide dosing recommendations. Clinical studies evaluating potential CNS effects have used 25 mg (either as a single dose or once daily [treatment durations ranged from 8 days to 9 weeks]) of a proprietary extract of S. tortuosum (standardized to a total alkaloid content for the 4 main Sceletium alkaloids [mesembrenone, mesembrenol, mesembrine, and mesembranol] of 0.4%).(Chiu 2014, Reay 2020, Terburg 2013)

S. tortuosum is typically available as a tincture, tablet, or capsule in unit doses of 50 to 200 mg of the dried, milled herbal material.(Gericke 2008)

In traditional use, a "plug" of dried, fermented S. tortuosum has been chewed to release its constituents. Alternatively, a fresh leaf applied directly to a tooth, or a drop of fresh leaf juice placed on the tongue has been used. A decoction or infusion may also be prepared.(SANBI 2021)

Ginkgo Biloba, turmeric, saw palmetto

Pregnancy / Lactation

Avoid use. Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

Information is lacking regarding interactions of S. tortuosum with drugs, foods, dietary supplements, or herbs. Because of reported psychoactive activity with S. tortuosum, caution should be used in individuals taking psychoactive drugs such as anxiolytics, sedatives, hypnotics, or antidepressants.

Adverse Reactions

Data are limited regarding adverse reactions associated with S. tortuosum use. In a proof-of-concept randomized controlled study, treatment-emergent adverse effects reported with S. tortuosum (Zembrin) that did not occur with placebo were weight gain (14%), increased appetite (10%), increased thirst (10%), and tiredness/fatigue (10%), as well as headache, chest pain, nausea, vomiting, constipation, genital discomfort, muscle rigidity, drowsiness, difficulty concentrating, confusion, and depression (5% for all).(Chiu 2014) Euphoric effects with intoxicating doses can be followed by sedation; however, the plant is not hallucinogenic and does not cause motor impairment. Chronic use does not appear to result in withdrawal upon discontinuation.(Gericke 2008)

Toxicology

Information regarding toxicity in humans is lacking. In animal studies, milled S. tortuosum added to feed in doses of 10 mg/kg once a day in healthy dogs and 100 mg/kg once a day in healthy cats had no toxic effects, and all body systems functioned within normal ranges.(Gericke 2008, Harvey 2011b)

In a study of Wistar rats, oral administration of a proprietary extract of S. tortuosum (Zembrin) at doses of 17.85, 35.7, and 71.4 mg/kg of body weight over 90 days showed no toxic effects, indicating a no-observed-effect level of 71.4 mg/kg.(Harvey 2011a) The same proprietary extract was administered to Wistar rats in a 14-day, repeated oral toxicity study at doses of 250, 750, 2,500, and 5,000 mg/kg daily; as well as in a 90-day, subchronic, repeated oral dose study at dosages of 100, 300, 450, and 600 mg/kg daily. No mortality or toxicity was observed in rats in the 14- or 90-day studies.(Murbach 2014)

References

Disclaimer

This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.

This product may adversely interact with certain health and medical conditions, other prescription and over-the-counter drugs, foods, or other dietary supplements. This product may be unsafe when used before surgery or other medical procedures. It is important to fully inform your doctor about the herbal, vitamins, mineral or any other supplements you are taking before any kind of surgery or medical procedure. With the exception of certain products that are generally recognized as safe in normal quantities, including use of folic acid and prenatal vitamins during pregnancy, this product has not been sufficiently studied to determine whether it is safe to use during pregnancy or nursing or by persons younger than 2 years of age.

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