Acute effects of Sceletium tortuosum (Zembrin), a dual 5-HT reuptake and PDE4 inhibitor, in the human amygdala and its connection to the hypothalamus.

Journal: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

Volume: 38

Issue: 13

Year of Publication: 2014

Affiliated Institutions:  ] Department of Psychology, Utrecht University, Utrecht, The Netherlands [] Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa.

Abstract summary 

The South African endemic plant Sceletium tortuosum has a long history of traditional use as a masticatory and medicine by San and Khoikhoi people and subsequently by European colonial farmers as a psychotropic in tincture form. Over the past decade, the plant has attracted increasing attention for its possible applications in promoting a sense of wellbeing and relieving stress in healthy individuals and for treating clinical anxiety and depression. The pharmacological actions of a standardized extract of the plant (Zembrin) have been reported to be dual PDE4 inhibition and 5-HT reuptake inhibition, a combination that has been argued to offer potential therapeutic advantages. Here we tested the acute effects of Zembrin administration in a pharmaco-fMRI study focused on anxiety-related activity in the amygdala and its connected neurocircuitry. In a double-blind, placebo-controlled, cross-over design, 16 healthy participants were scanned during performance in a perceptual-load and an emotion-matching task. Amygdala reactivity to fearful faces under low perceptual load conditions was attenuated after a single 25 mg dose of Zembrin. Follow-up connectivity analysis on the emotion-matching task showed that amygdala-hypothalamus coupling was also reduced. These results demonstrate, for the first time, the attenuating effects of S. tortuosum on the threat circuitry of the human brain and provide supporting evidence that the dual 5-HT reuptake inhibition and PDE4 inhibition of this extract might have anxiolytic potential by attenuating subcortical threat responsivity.

Authors & Co-authors:  Terburg David D Syal Supriya S Rosenberger Lisa A LA Heany Sarah S Phillips Nicole N Gericke Nigel N Stein Dan J DJ van Honk Jack J

Study Outcome 

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Statistics
Citations :  Anderson IM, McKie S, Elliott R, Williams SR, Deakin JF. Assessing human 5-HT function in vivo with pharmacoMRI. Neuropharmacology. 2008;55:1029–1037.
Authors :  8
Identifiers
Doi : 10.1038/npp.2013.183
SSN : 1740-634X
Study Population
Male,Female
Mesh Terms
Adolescent
Other Terms
Study Design
Cross Sectional Study
Study Approach
Country of Study
South Africa
Publication Country
England