S. tortuosum has been traditionally used to manage anxiety and depression, as well as to enhance mood, cognitive activity, and memory.
Scientific Family
Mesembryanthemoideae (subfamily)
S. tortuosum is a perennial decumbent or climbing succulent plant indigenous to South Africa.Gericke 2008, Harvey 2011 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

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. Kanna should not be confused with the ganna plant (Salsola dealata Botsch.).Smith 1996

S. tortuosum has a long history of use in South Africa and is one of the region's most coveted botanical assets. It is traditionally prepared by 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 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, regulate sleep, and quench thirst and hunger, as well as for its masticatory, analgesic, narcotic, sedative, antispasmodic, and GI effects. A small amount of S. tortuosum has sometimes been added to a teaspoon of breast milk or mixed with a small amount of sheep tail fat to treat colic in infants. It has also been used for spiritual and social purposes.Gericke 2008, Mannetti 2011, Mitchell 2004, Nielsen 2004, Setshedi 2012, Smith 2011, Stafford 2009

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 substantiated that sunlight and aqueous conditions are required to facilitate this transformation and 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. tortuosumNielsen 2004 and is a potent selective serotonin (5-HT) reuptake inhibitor (SSRI).Gericke 2008, Harvey 2011, 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 S. tortuosum's acetylcholinesterase-inhibiting ability.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 cytochrome P17A1 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 2011, Harvey 2011, Mitchell 2004, Setshedi 2012, Shikanga 2011, Stafford 2009 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.

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 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, which 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 2011

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

Other limited case reports are available.

Cognitive function
Animal data
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 2011

Clinical data
A pilot randomized, placebo-controlled, crossover study evaluated the neurocognitive effects of S. tortuosum extract (Zembrin 25 mg) administered once daily for 3 weeks (total study duration of 9 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, composite memory) or for reaction speed and composite attention. According to the Hamilton Depression Rating Scale, positive changes were observed for mood and sleep. Vital signs were stable throughout the study. Subjects treated with S. tortuosum extract reported transient GI discomfort.Chiu 2014

Other uses
Drug dependence
S. tortuosum has been used to reduce drug dependenceGericke 2008, Lubbe 2010, Shikanga 2011, Shikanga 2012; limited case reports are available.

Quality of sleep
Limited case reports are available.

S. tortuosum has been used as a sedative in the form of a tea, decoction, or tincture. It has been traditionally used as a local anesthetic and analgesic for extracting teeth from the lower jaw.Gericke 2008, Smith 1996 When the S. tortuosum fraction mesembrine was administered to male Sprague-Dawley rats, analgesic properties were observed without abuse liabilities or ataxia.Loria 2014

One study suggests that mesembrenone has cytotoxic activity against a murine nontumoral fibroblast cell line and a human tumoral cell line (Molt4).Gericke 2008, Harvey 2011 Mesembrenone was moderately effective and less toxic than other amaryllidaceous alkaloids.Smith 1996 Further studies are necessary.

Compounds of S. tortuosum are being evaluated for their antimalarial activity.Setshedi 2012

In traditional use, a plug of dried fermented S. tortuosum was chewed to release its constituents. Alternatively, a fresh leaf was applied directly to a tooth, or a drop of fresh leaf juice placed on the tongue. A decoction or infusion may also be prepared.South African Biodiversity Institute 2016

S. tortuosum is available as a tincture, tablet, or capsule (in unit doses of 50 to 200 mg of the dried milled herbal material).Gericke 2008 Animal models suggest an S. tortuosum extract dose of 2 g/kg body weight.Harvey 2011 In Wistar rats, an extract of unfermented S. tortuosum 5 to 20 mg/kg/day reduced psychological stress; however, inflammatory responses suggestive of intolerance and varying degrees of Th1 immune suppression were also observed. Further studies are needed to determine an appropriate dosage.Smith 2011