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- Sceletium (Sceletium tortuosum)
- Zembrin®
- Safety
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Date:
06-14-2013 | HC# 051331-474
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Re: Zembrin® (Sceletium Extract) Is Safe and Well Tolerated in a Trial in Healthy Adults
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. February 26, 2013; [epub ahead of print]. doi:
10.1089/acm.2012.0185.
Sceletium
(Sceletium tortuosum) has a long
history of use as a medicinal plant in South Africa, home to these authors. In
1728, it was proclaimed "the greatest cheerer of the spirits, and the
noblest restorative in the world."1 According to the authors,
sceletium is used to relieve thirst, hunger, and fatigue, and for its
restorative, mood-elevating, and sedative effects, including its therapeutic
use for anxiety and depression. Intoxication and euphoria are also reported
with its use.2 In case studies, anxiolytic and antidepressant
activities have been observed with consumption of sceletium tablets and
capsules.3 These authors conducted a randomized, double-blind,
parallel-group, placebo-controlled trial to evaluate the safety and tolerability
of two different doses of Zembrin® (extract manufactured by Gehrlicher
GmbH; Eurasburg, Germany; capsules manufactured by Pharmaceutical Contractors [Pty]
Ltd.; Isando, South Africa), a proprietary commercial dry extract of sceletium,
in healthy adults.
The
active ingredient of Zembrin is a 2:1 dry aqueous-ethanolic extract of the
entire aboveground portions of naturally occurring sceletium, with an alkaloid
content not less than 0.38% by weight. Safe daily doses of sceletium raw
material are reported to range from 50 mg to 5,000 mg. The authors selected low
doses of 8 mg and 25 mg of Zembrin (equivalent to 16 mg and 50 mg, respectively,
of sceletium), considering the doses to be safe and to have potential for
inclusion in functional food and dietary supplement products. The Zembrin used
in this study was standardized to 0.4% W/W total for the 4 alkaloids
mesembrenol, mesembrenone, mesembrine, and mesembranol. Each gelatin capsule
contained 0 mg, 8 mg, or 25 mg of sceletium dry extract, as well as various
excipients.
A
screening visit was followed by a 2-week placebo run-in period during which 37
subjects recorded their daily use of placebo medication to assess compliance.
At visit 3, the subjects were randomly assigned to 1 of the following 3 treatment
groups for 3 months: 12 subjects were allocated to the 8 mg Zembrin group, 12
to the 25 mg Zembrin group, and 13 to the placebo group. All but 1 subject completed
the trial. The 37 healthy men and nonpregnant women (no gender differentiation
provided) were aged between 18 and 55 years, weighed >50 kg (>110.2 lb),
and had a body mass index ranging from 18.5 to 29.9 kg/m2.
Visits
3, 4, 5, and 6 were scheduled monthly. Safety assessments performed at the
screening visit and at visits 4, 5, and 6 included vital signs, physical
examination, laboratory test, 12-lead electrocardiogram (ECG), and the recording
of adverse events (AEs). At visits 2, 3, 4, and 5, the subjects were given a
diary and asked to record the occurrence of AEs, their daily use of the study
product, and the intake of other medications.
The
authors report that the greatest incidence of AEs occurred in the placebo
group, followed by the 25 mg and 8 mg Zembrin groups. Twenty-two of the 37 total
assigned subjects (59%) experienced at least 1 AE. Four of the 12 subjects (33.3%)
in the 8 mg group reported 6 AEs. Seven of the 12 subjects (58.3%) in the 25 mg
group reported 14 AEs, and 11 of the 13 subjects (84.6%) in the placebo group
reported 22 AEs.
Headache
was the most common AE, with 8 incidences reported by 7 of the 37 subjects
(18.9%). Of those, 4 occurred in 4 subjects in the placebo group, 3 in 2
subjects in the 25 mg Zembrin group, and 1 in 1 subject in the 8 mg Zembrin group.
Other AEs included abdominal pain (5 incidences in 3 of the 13 subjects in the
placebo group), upper respiratory tract infection (4 incidences in 4 of the 13
subjects who received placebo), and influenza (3 incidences in 3 subjects; 1
from each group).
All
but 2 AEs were mild or moderate and were considered unrelated to the study
medication. The 2 severe AEs were reported in the placebo group. One subject
reported abdominal pain, which was considered as possibly related to the study
product; and 1 subject who complained of headache, which was considered as probably
related to the study product, withdrew from the trial.
The
authors reported no marked, clinically relevant differences in the changes in
vital signs among the 3 treatments, except for a difference in diastolic blood
pressure (DBP) between the placebo and the 8 mg Zembrin groups. In those in the
8 mg group, a mean increase in DBP of 1.92 mmHg occurred from the screening visit
to visit 6; the subjects in the placebo group experienced a mean decrease in
DBP of 6.17 mmHg. This resulted in a mean difference of 8.08 mmHg (95% confidence
interval: 1.51-14.65) between those 2 treatments (P=0.02). No such significant
difference in DBP was seen between the 25 mg Zembrin group and the placebo
group.
Other
safety results showed no differences among the 3 treatments in ECG or physical
examination findings during the 3 months, and no significant changes were
observed in laboratory parameters or in body weight.
Five
subjects offered positive comments about changes in their health. These
comments from 1 subject (8.3%) in the 8 mg Zembrin group, 3 subjects (25%) in
the 25 mg Zembrin group, and 1 subject (7.7%) in the placebo group included sleeping
better at night, coping better with stressful situations, and feeling better in
general.
According
to the authors, the spectrum of sceletium uses suggests a dose response. The
lowest doses are ingested at the food side of the spectrum, higher doses at the
botanical medicine side, and the highest doses at the intoxicating end of the
spectrum. "In addition to dose-response for total alkaloid content, the
alkaloid composition is likely to be a key factor that determines effects and
adverse effects," write the authors.
The
results of this trial show that both treatments of Zembrin at doses of 8 mg and
25 mg once daily for 3 months were well tolerated and safe.
One
of the authors (Nigel Gericke) discloses that he is the Director of Medical and
Scientific Affairs of HG&H Pharmaceuticals (Pty) Ltd, the company that
developed Zembrin.
―Shari
Henson
References
1Kolben P. Medley G,
trans. The Present State of the Cape of
Good-Hope. Vol. 1, 2nd ed. London, UK: Printed for W. Innys and
R. Manby; 1738.
2Gericke N, Viljoen AM.
Sceletium—a review update. J
Ethnopharmacol. 2008;119(3):653-663.
3Gericke N. Clinical
application of selected South African medicinal plants. Australian Journal of Medical Herbalism. 2001;13(1):3-7, 9-11,
13-15.
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