The tradition of human use of the Sceletium plant goes back centuries if not millennia, but only in the past 15 years Sceletium, in its standardized form as the brand Zembrin®, was systematically tested in vitro and in vivo studies for its nutritional properties that might be relevant to the ethnopharmacological uses.
In 2014 a peer-reviewed published clinical study evaluated the cognitive effects of Zembrin®, as well as its safety and tolerability in healthy subjects. Zembrin® has been used in the form of hydroethanolic extract of a select variety of Sceletium tortuosum plant standardized to contain 0.35-0.45% total alkaloids (mesembrenone and mesembrenol ≥60%, and mesembrine <20%). Healthy subjects received either 25 mg capsules of Zembrin® or matching placebo once daily for three weeks. The average age of test subjects was 54.6 years old, with nine male and 12 female participants. Zembrin® statistically significantly improved cognitive and executive functions (performance of daily tasks) compared with the placebo group. In addition, the improvements in mood and sleep patterns were found in the course of the study. Zembrin® was well tolerated and no subjective or objective side effects were reported during the three weeks of study. The study authors suggested that positive effects of Zembrin® were due to preserving neurohormones involved in maintaining communication between brain cells, facilitating effective flow of information in the neural system.
Another interesting study evaluated effects of Zembrin® on anxiety-related activity of the brain in healthy human subjects. In this placebo-controlled study, 16 healthy participants were screened with a non-invasive neuroimaging technique during the performance of an assigned emotional task, to record their reactions to pictures of fearful faces. The natural reaction to fear was attenuated after a single 25 mg dose of Zembrin® as compared to matching placebo. These results demonstrated, for the first time, the attenuating or “sheltering” effects of Sceletium versus reaction to threat and fear of the human brain, providing supporting evidence that standardized extract of this plant may have potential to prevent excess anxiety by alleviating our atavistic response to threat.
Clinical trials show Zembrin® does not cause dependency even with long-term use.
Previously to the aforementioned studies, Zembrin® was evaluated for safety and tolerability of two doses (8 mg and 25 mg once daily) and matching placebo in healthy adult volunteers of both sexes for three months. There were no apparent differences between the three treatments with regard to vital signs, 12-lead ECG, body weight, and physical examination from screening to the end of the three-month treatment period. No significant changes were observed in blood testing parameters between initial screening and the end of the study. Both doses of Sceletium tortuosum extract were well-tolerated. The most commonly reported adverse effect was headache, followed by abdominal pain and upper respiratory tract infections, all with greater incidence in the placebo group than in the treatment groups. Unsolicited positive effects on well-being were noted in patient diaries by some participants taking Zembrin®, including improved coping ability with stress and sleep. Both doses of Sceletium tortuosum extract (Zembrin®) (8 mg and 25 mg) were well tolerated when used by healthy human subjects once daily for three months.
In an in vitro published peer-review study a standardized extract of Zembrin® and its three main alkaloids— mesembrine, mesembrenone and mesembrenol—were tested for their biological properties that might be relevant to the formula’s ethnopharmacological uses. The extract and its main components increased bioavailability of neurohormones responsible for neural conductivity and communication, and did not have toxic effects on cultured cells. Mesembrine and mesembrenone were the most biologically active alkaloids. This in vitro activity of Sceletium tortuosum extract may explain the positive clinical effects of Zembrin® in healthy human volunteers.