Differential impact of extracts from distinct Sceletium tortuosum chemotypes on central neurotransmitter concentrations in C57BL/6 mice

Sceletium tortuosum, also known as kanna, or kougoed, has long been an integral part of the traditional medicinal practices of the San and Khoikhoi peoples of Southern Africa. Among the various Sceletium species, S. tortuosum is used for its mood-enhancing properties, attributed to the structurally related mesembrine-type alkaloids found therein. While significant research has focused on mesembrine and mesembrenone, the therapeutic potential of extracts from plants that produce more of the so-called "minor alkaloids", remains unexplored.

To assess the CNS modulatory effects of two chemotypes of S. tortuosum, wild-collected from two different geographic locations in South Africa (Touwsrivier and De Rust), each featuring different alkaloid profiles and with elevated minor alkaloid concentrations.

Extracts from these chemotypes, as well as a vehicle control and a commercial extract, were administered to four groups of mice for 35 days. Mice were then euthanised, and their frontal cortices, striata and hippocampi dissected. Serotonin, dopamine, noradrenaline, glutamate, and gamma-aminobutyric acid (GABA) concentrations were analysed using LC-MS.

Both chemotypes, compared to both control and commercial extract exposure, robustly increased noradrenaline and decreased GABA concentrations in all regions of the mouse brain analysed.

This finding may support a mood-enhancing effect of S. tortuosum and indicates its potential to modulate anxiety and stress processing, attention, and alertness. Alkaloid profiling further suggests that the mesembrine alcohols and sceletium A4 may be important contributors in driving these neurochemical changes.