Evid Based Complement Alternat Med. 2014;2014:682014. doi: 10.1155/2014/682014. Epub 2014 Oct 19.

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 S¹, Gericke N², Farina-Woodbury M³, Badmaev V⁴, Raheb H⁵, Terpstra K⁵, Antongiorgi J³, Bureau Y⁵, Cernovsky Z¹, Hou J⁵, Sanchez V⁵, Williams M⁵, Copen J⁶, Husni M⁷, Goble L⁵.

Author information

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

Abstract

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 n = 21) 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 (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 ClinicalTrials.gov NCT01805518.