Gertsch Group

Institute of Biochemistry and Molecular Medicine, University of Bern, Switzerland

Amazing Liverworts - the true link to cannabinoid research

Amazing Liverworts - the true link to cannabinoid research
Jurg Gertsch - Mon Oct 29, 2018 @ 09:45AM
Comments: 4

Some years ago, we became interested in the evolution of endogenous cannabinoids, the lipids that our body produce from arachidonic acid to make cannabinoids that activate cannabinoid receptors in our brain and other tissues in the body. Surprisingly, we found that already lower organisms, starting with algae and lower plants, make both 2-AG and anandamide and contain high amounts of free arachidonic acid.  However, higher plants, the seedplants (angiosperms), do not contain these lipids anymore. The reason for this is unclear at this point. This work was published last year in Scientific Reports ( Based on the pioneering work of Prof. Asakawa and coworkers and other phytochemists working on mosses and liverworts in combination the "science informed drug community", we found another quite unexpected link to liverworts. There is a THC similar compound (cis-perrottetinene) which is produced by these bryophytes, a convergent evolution which is quite amazing. Few Radula species generate this diastereoisomer of THC that is not generally found in Cannabis. Moreover, the alkyl chain of perrottetinene is benzylated. Interestingly, several years ago, Radula marginata suddenly started to be sold on the internet as a legal high with rather obscure reports from some users. This prompted us to scientifically investigate this interesting matter in order to provide a scientific basis. This was also interesting as cis-THC was said to be inavtive (though the early work in the 1970s in the lab of Prof. Mechoulam only relied on animal data as the receptors were not cloned yet. Few days ago, our study was published in Science Advances ( The popular conclusion from our work is that the natural product cis-perrottetinene (cis-PET) is a bioactive cannabinoid because it activates cannabinoid receptors very specifically, similar to THC. However it is less potent and shows an interesting difference that makes it potentially interesting. Cis-PET modulates the generation of prostaglandins differently from THC and overall shows the benefits of low THC. Therefore, we believe that the "Radula high" is absolutely not the intersting aspect of this natural product but rather the potential medical application of both the pure compound or potentially even the moss. In collaboration with Prof. Carreiras group, the natural product and its non-natural trans-variant trans-PET were generated synthetically, employing an elegantg stereoselective approach. In light of the Convention on Biological Diversity (CBD) signed by Switzerland in the 1990s, we did not bioprospect this cannabinoid by collecting the material in situ. The biogenetic resources belong to the countries they are generated in (evolved). In fact, all three Radula species that have been shown to contain this molecule grow quite locally and in ecologic niches in Japan, New Zealand and Costa Rica and thus are not very widesperad. We also tested our local Radula complanata species that grows quite abundantly but did not find cis-PET in this plant. A pity! I am very interested to find out whther the claims about ethnobotanical or ethnopharmacological uses of the Radula marginata by the Maori communities in New Zealand are substantial as I did not find any scientitic data on this topic. The Maori did not discover the psychoactivity of Radula marginata, or am I mistaken?

Comments: 4


1. Chen   |   Mon Oct 29, 2018 @ 10:51AM

Thanks for sharing this extremely interesting work - so liverworts make both endocannabinoids and THC-like compounds? Any idea what they use them for?

2. Maoriforce   |   Tue Nov 06, 2018 @ 08:30AM

Hi - the Maori did discover the psychoactivity of this moss, this you can believe me. Only because science shows this now does not mean that Maori people are stupid.

3. Jurg Gertsch   |   Tue Nov 20, 2018 @ 05:05PM

I am not so sure whether the Maori actually discovered this. To me it seems more that the finding was inspired by phytochemistry. In the comprehensive Maori ethnobotanical literature few liverworts are mentioned, but not the Radula species.

4.  |  my website   |   Thu Jul 11, 2019 @ 08:37AM

Hey I read your post its very very good best post keep up this work thanks.

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