Sceletium: Tapping a web of alkaloids

Kanna is an incredibly diverse plant- this blog will discuss and analyze the spectrum of alkaloids present in sceletium- as of my writing this article there are over 25 know / identified alkaloid compounds in the sceletium species that span across 4 main classes:

-Mesembrine (3a‐aryl‐cis‐octahydroindole skeleton group, roughly 15 known alkaloids have been identified thus far)

-Sceletium A4 (newely discovered, structural relation to another alkaloid, tortuosamine, lone member of this subgroup)

-Joubertiamine (biogenetically closely related to mesembrane)

-Tortuosamine

 For consistency we'll initially stick to discussing these three alkaloids as they're what most extract descriptions on the market discuss:

-Mesembrine

-Mesembrenone

-Delta 7 Mesembrenone

 First let's discuss Mesembrine and the various research- often the highest alkaloid % comparatively by weight.

Based on the available research it's my understanding this alkaloid, and the alkaloids similar are likely dominantly responsible for the potential uplifting effect- a serotonin reuptake inhibitor. 

As well studies suggest mesembrine as a weak PDE4 inhibitor- potentially relating to positive cognitive effects such as wakefulness or memory.

A mentionable component as of recently is the suggestion by researchers that mesembine is a monoamine releasing agent (MRA)- this could be another action relating mesembrine to potential anti-depressant effects. (1)

Mesembrine was the most active alkaloid against the 5-HT transporter (3) -contributes to the regulation of serotonergic neurotransmission through the reuptake of 5-HT in the synaptic clef

Let's discuss Mesembrenone 

Mesembrenone shares similarities with contemporary synthetic antidepressants, displaying strong potency with an IC50 value below 1 μM. It acts as a selective inhibitor of the serotonin transporter (SERT), essentially functioning as a selective serotonin reuptake inhibitor (Ki = 27 nM). Additionally, it also serves as an inhibitor of phosphodiesterase 4 (PDE4). (2)

Mesembrenone is active against the 5-HT transporter (3)

Delta 7 Mesembrenone

"Another alkaloid found in S. tortuosum is delta 7 mesembrenone, D7 is a potent antioxidant, and a powerful inhibitor of tyrosinase activity, kojic acid at high doses had an almost identical effect on this enzyme" (4)

 To summarize these actions into effects isn't exactly easy, especially since users will experience different things. 

Based on the research cited, and the specific mechanisms targeted- it appears mesembrine would act more stimulating, while mesembrenone would be more relaxing. The psychoactive activity if any at all of delta 7 is still to be determined- although it does exhibit anti-inflammatory effects I could see this playing a role in how the other alkaloids interact.

  Examples of more alkaloids 

4'-O-demethylmesembrenol

Mesembrine 

Mesembrenone

Mesembrane

N‐formyltortuosamine

4′‐O‐demethylmesembrenone

Sceletenone (5)

Joubertiamine (similar to mesembrane) Arndt and Kruger in 1970

Dihydrojoubertiamine  (similar to mesembrane) Arndt and Kruger in 1970

Dehydrojoubertiamine  (similar to mesembrane) Arndt and Kruger in 1970

This is a non-exhaustive list, check back for an update.

This blog is not written by a health professional- FDA does not approve kanna or any alkaloids present to treat, cure or help any condition. Contact your health provider if trying any new herbal supplement- and as always consuming kanna or kanna extracts of any kind are at your own risk.

 Citations: 

https://en.wikipedia.org/wiki/Mesembrine (1)

https://en.wikipedia.org/wiki/Mesembrenone (2)

https://www.sciencedirect.com/science/article/abs/pii/S0378874111005113?via%3Dihub (3)

https://www.sciencedirect.com/science/article/pii/S2405844020323227 (4)

https://www.intechopen.com/chapters/53426 (5)