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Approximately 300 million people around the globe suffer from major depressive disorder (MDD) (World Health Organization, 2018; Willner et al., 2013). Due to the complex neurobiology of MDD, only 30–40% of patients respond to current antidepressants, emphasizing a pressing need for improved novel and alternative treatments (Trivedi et al., 2006; Willner et al., 2013).

Due to their selective actions to bolster monoamine levels, currently prescribed antidepressants appear insufficient to engender full and sustained remission of the illness (Akil et al., 2018; World Health Organization, 2018). Furthermore, side effects and a delayed onset of action (Bet et al., 2013; Carhart-Harris and Nutt, 2017) compromises patient compliance.

Many herbal substances have demonstrated antidepressant effects in preclinical and clinical studies, often with similar mechanisms to that of standard antidepressants (Fajemiroye et al., 2016; Sarris, 2018). Additionally, these preparations may exhibit multi-target mechanisms of action on many different neurobiological processes implicated in MDD (Fajemiroye et al., 2016; Sarris, 2018). While most of these natural substances show potential as monotherapy, others indicate more favourable results when combined with traditional antidepressants (Akhondzadeh et al., 2003). Consequently, the World Health Organization initiated a traditional medicine strategy for 2014–2023 stating that evidence-based research be utilized to evaluate the safety and efficacy of complementary medicines (World Health Organization, 2013). Furthermore, in resource constricted countries, up to 80% of the population depends on herbal medicines for primary healthcare, albeit with a lack of supporting scientific data (Oyebode et al., 2016). It is with this motivation that a standardized extract of the indigenous South African plant, Sceletium tortuosum (ST), has attracted a great deal of interest (Olatunji et al., 2021; Brendler et al., 2021).

For generations, the indigenous Khoisan people have used ST as a mood-elevator, analgesic, hypnotic, anxiolytic, thirst and hunger suppressant, and for its intoxicating/euphoric effects (Gericke and Viljoen, 2008; Brendler et al., 2021).

The characteristic alkaloid profile of Sceletium tortuosum, including mesembrine, mesembrenone, mesembrenol, and mesembranol (Krstenansky, 2017), presents with subtly different neuro-psycho-pharmacological actions (Olatunji et al., 2021) that may underlie the above-mentioned therapeutic properties. These actions include up-regulating vesicular monoamine transporter 2 (VMAT-2), serotonin transporter (SERT) inhibition, inhibition of phosphodiesterase 4 (PDE4) activity, anti-inflammatory properties, inhibition of monoamine oxidase A (MAO-A) and inhibition of the noradrenaline (NA) and dopamine (DA) transporters (NAT, DAT) (Olatunji et al., 2021).

Clinically, Sceletium Tortuosum also shows a relatively low side effect profile (Krstenansky, 2017; Murbach et al., 2014)

Clearly, further exploration of the potential antidepressant actions of Sceletium Tortuosum could prove invaluable due to its multi-modal mechanisms of action that align well with the pathophysiological mechanisms of MDD (Brand et al., 2015).

#serobrine #MDD #depression #neuro-psycho-pharmacological #Scletium Tortuosum

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