Clinical Research

Proof-of-Concept Randomized Controlled Study of Cognition Effects of the Proprietary Extract Sceletium tortuosum (Zembrin®)

Proof-of-Concept Randomized Controlled Study of Cognition Effects of the Proprietary Extract Sceletium tortuosum (Zembrin) Targeting Phosphodiesterase-4 in Cognitively Healthy Subjects: Implications for Alzheimer’s Dementia

Chiu, Simon & Gericke, Nigel & Woodbury, Michel & Badmaev, Vladimir & Raheb, Hana & Terpstra, Kristen & Antongiorgi, Joalex & Bureau, Yves & Cernovsky, Zack & Hou, Jirui & Sanchez, Veronica & Williams, Marissa & Copen, John & Husni, Mariwan & Goble, Liz



Converging evidence suggests that PDE-4 (phosphodiesterase subtype 4) plays a crucial role in regulating cognition
via the PDE-4-cAMP cascade signaling involving phosphorylated cAMP response element binding protein (CREB). Objective.The
primary endpoint was to examine the neurocognitive effects of extract Sceletium tortuosum (Zembrin) and to assess the safety and
tolerability of Zembrin in cognitively healthy control subjects. Method. We chose the randomized double-blind placebo-controlled
cross-over design in our study. We randomized normal healthy subjects (total 𝑛 = 21) to receive either 25mg capsule Zembrin
or placebo capsule once daily for 3 weeks, in a randomized placebo-controlled 3-week cross-over design.We administered battery
of neuropsychological tests: CNS Vital Signs and Hamilton depression rating scale (HAM-D) at baseline and regular intervals and
monitored side effects with treatment emergent adverse events scale. Results. 21 subjects (mean age: 54.6 years ± 6.0 yrs; male/female ratio: 9/12) entered the study. Zembrin at 25mg daily dosage significantly improved cognitive set flexibility (𝑃 < 0.032) and executive function (𝑃 < 0.022), compared with the placebo group. Positive changes in mood and sleep were found. Zembrin
was well tolerated. Conclusion. The promising cognitive enhancing effects of Zembrin likely implicate the PDE-4-cAMP-CREB
cascade, a novel drug target in the potential treatment of early Alzheimer’s dementia. This trial is registered with

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