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Evidence-Based Complementary and Alternative Medicine
Volume 2014, Article ID 682014, 9 pages
Research Article

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

1Lawson Health Research Institute, Lab FB125, 268 Grosvenor Street, London, ON, Canada N6A 4V2
2Department of Psychiatry, University of Western Ontario, London, ON, Canada N6A 3K7
3Medical and Scientific of HG & H Pharmaceuticals (Pty) Ltd., 193 Bryanston Drive, Bryanston 2192, South Africa
4Department of Psychiatry, School of Medicine, University of Puerto Rico, San Juan, PR 00936-5067, USA
5Medical and Scientific Affairs, P L Thomas & Co., Inc., Morristown, NJ 07960, USA
6Department of Psychiatry, Island Medical Program, University of Victoria, University British Columbia Extended Medical Campus, Victoria, BC, Canada V8W 2Y2
7Department of Psychiatry, Northern Ontario School of Medicine, Thunder Bay, ON, Canada P7B 5E1

Received 21 May 2014; Revised 16 August 2014; Accepted 2 September 2014; Published 19 October 2014

Academic Editor: Kuzhuvelil B. Harikumar

Copyright © 2014 Simon Chiu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Introduction. 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 ) to receive either 25 mg 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 25 mg daily dosage significantly improved cognitive set flexibility () and executive function (), 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 NCT01805518.