Plants of the genus Sceletium are among the most commercially promising plants
indigenous to South Africa, with potential for use in dietary supplements,
natural medicines, and veterinary and pharmacologic products. Since the first
ethnopharmacological review of this genus by Smith et al. in 1966, several
advances in Sceletium research have
been made, and an increasing number of products containing Sceletium are becoming available. Commercial plantations have been
established to produce a more consistent-quality crop for use in manufacturing
such products. The purpose of this review was to provide a historical overview
of the clinical applications of Sceletium
and recent developments concerning the chemistry and pharmacology of this genus.
The genus name, Sceletium, is derived from the word sceletus, which means skeleton. This designation refers to the
prominent lignified veins visible on the leaves of this plant. Sceletium species are distributed
throughout the southwestern portion of South Africa in arid environments and
are distinguishable on the basis of different vegetative, flower, fruit, and
seed characteristics. The fruit capsule contains several kidney-shaped seeds
that range in color from brown to black, and the flowers of this genus can be
white, yellow, or pale pink.
Vernacular names for this genus include kanna (Khoi) and kougoed (Afrikaans). The earliest unambiguous illustration of a Sceletium plant was found in the journal
of Cape of Good Hope Governor Simon van der Stel's from his expedition to
Namaqualund in 1685. In 1738, Kolben noted that kanna was the "greatest Chearer [sic] of the Spirits, and the
noblest Restorative in the World." Lewin noted in 1924 that Kolben, under
the name kanna or channa, had been referring to the plant
root used by the Hottentots as a means of enjoyment, which they "chewed,
kept in their mouths for some time, thus becoming excited and
intoxicated." The name channa
refers to certain species of Sceletium,
including S. expansum and S. tortuosum, both of which were
illustrated in the 18th century. The Afrikaans vernacular kougoed was first recorded for S. tortuosum in approximately 1830.
According to Meiring (1898), S. tortuosum
was widely used for its soporific effect on young children; one or two drops of
fresh juice from the plant would be given to children, "who would enjoy a
deep quiet rest for a few hours." It has also been reported that the
leaves of S. tortuosum were chewed to
relieve toothaches and abdominal pain. More recently (20th century),
extracts from the plant have been used to treat colic in infants.
Sceletium contains several alkaloids, which were
categorized by Jeffs et al. (1982) into 4 categories: 1) 3a-aryl-cis-octahydroindoles (e.g., mesembrine),
2) C-secomesembrine alkaloids (e.g., joubertiamine), 3) alkaloids containing a
2,3-disubstituted pyridine moiety and two nitrogen atoms (e.g., Sceletium alkaloid A4), and
4) a ring C-seco Sceletium alkaloid
A4 group (e.g., tortuosamine). In 1966, Gerbaulet documented the existence of eight
species of the genus Sceletium. S. strictum, S. subvelutinum (= S. varians),
S. tortuosum, S. joubertii, and S. namaquense
are the most well-studied. S. joubertii
and S. namaquense are now considered
to be synonymous with S. tortuosum. Most
of the research on Sceletium
alkaloids has involved isolation and structural elucidation. Little is known
about the distribution and chemotaxonomic patterns. Furthermore, comparative
analytical results between species are scarce. A concise summary of Sceletium alkaloids was recently
compiled by Gaffney (2006).
Mesembrine and
related compounds have potential use in pharmaceuticals for the management of
psychiatric and psychological conditions, such as anxiety, depression, drug
dependence, bulimia, and obsessive-compulsive disorder. This alkaloid has been
confirmed to be a serotonin-uptake inhibitor. The inhibition of serotonin
uptake is one of the possible mechanisms whereby intake of adequate doses of Sceletium can affect mood and the sleep state. Mesembrenone
has also been shown to have cytotoxic activity against a murine non-tumoral
fibroblast cell line and a human tumoral cell line.
Of the known Sceletium species, S.
tortuosum has been researched the most and has been used most frequently commercially.
Products containing S. tortuosum are
increasingly becoming more available in the marketplace as natural supplements
to combat stress, anxiety, and depression. The usual recommended dose of these
supplements ranges from 50 to 200 mg, and no severe adverse effects have been
reported at these doses. The authors note that the "pharmacologic study of
Sceletium is in its infancy" and
that "a great deal of work remains to be done." The focus of research
for more than 100 years has been on the alkaloid constituents of this genus. However,
the non-alkaloid constituents may provide a new avenue of research in the
future. The authors suggest that placebo-controlled clinical trials be
conducted to establish safety and efficacy parameters so that the health
potential of this plant can be maximized.