Abstracts:

The South African endemic plant Sceletium tortuosum has long been used traditionally by the San and Khoikhoi people, and later by European colonial farmers, as a psychotropic agent in tincture form as a chewing and medicinal agent. In the last decade, the plant has attracted increasing attention for its potential applications in promoting well-being and alleviating stress in healthy individuals, as well as treating clinical anxiety and depression. The pharmacological effects of a standardized extract of the plant (zembrin) have been reported to be dual PDE4 inhibition and 5-HT reuptake inhibition, a combination reported to offer potential therapeutic benefits. Here, we tested the acute effects of zembrin administration in a Pharmaco-fMRI study that focused on anxiety-related activity in the amygdala and associated neurocircuitry. In a double-blind, placebo-controlled cross-over design, 16 healthy participants were scanned during performance in a perceptual load and an emotion-matched task. Amygdala reactivity to fearful faces under low perceptual load conditions was attenuated after a single 25-mg dose of zembrin. Subsequent connectivity analysis of the emotion matching task showed that amygdala-hypothalamus coupling was also reduced. These results demonstrate for the first time the attenuating effect of Sceletium tortuosum on the human brain threat circuit and provide supportive evidence that the dual 5-HT reuptake inhibition and PDE4 inhibition of this extract may have anxiolytic potential by attenuating the subcortical threat response. Neuropsychopharmacology Online Advance Publication, August 21, 2013; doi:10.1038/npp.2013.183