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dc.contributor.author
Chicca, Andrea
dc.contributor.author
Schafroth, Michael A.
dc.contributor.author
Reynoso-Moreno, Inés
dc.contributor.author
Erni, Reto
dc.contributor.author
Petrucci, Vanessa
dc.contributor.author
Carreira, Erick M.
dc.contributor.author
Gertsch, Jürg
dc.date.accessioned
2018-12-05T10:05:28Z
dc.date.available
2018-11-09T05:51:22Z
dc.date.available
2018-12-05T10:05:28Z
dc.date.issued
2018-10-03
dc.identifier.issn
2375-2548
dc.identifier.other
10.1126/sciadv.aat2166
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/302458
dc.identifier.doi
10.3929/ethz-b-000302458
dc.description.abstract
Phytochemical studies on the liverwort Radula genus have previously identified the bibenzyl (−)-cis-perrottetinene (cis-PET), which structurally resembles (−)-Δ9-trans-tetrahydrocannabinol (Δ9-trans-THC) from Cannabis sativa L. Radula preparations are sold as cannabinoid-like legal high on the internet, even though pharmacological data are lacking. Herein, we describe a versatile total synthesis of (−)-cis-PET and its (−)-trans diastereoisomer and demonstrate that both molecules readily penetrate the brain and induce hypothermia, catalepsy, hypolocomotion, and analgesia in a CB1 receptor–dependent manner in mice. The natural product (−)-cis-PET was profiled on major brain receptors, showing a selective cannabinoid pharmacology. This study also uncovers pharmacological differences between Δ9-THC and PET diastereoisomers. Most notably, (−)-cis-PET and (−)-trans-PET significantly reduced basal brain prostaglandin levels associated with Δ9-trans-THC side effects in a CB1 receptor–dependent manner, thus mimicking the action of the endocannabinoid 2-arachidonoyl glycerol. Therefore, the natural product (−)-cis-PET is a psychoactive cannabinoid from bryophytes, illustrating the existence of convergent evolution of bioactive cannabinoids in the plant kingdom. Our findings may have implications for bioprospecting and drug discovery and provide a molecular rationale for the reported effects upon consumption of certain Radula preparations as moderately active legal highs.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
AAAS
en_US
dc.rights.uri
http://creativecommons.org/licenses/by-nc/4.0/
dc.title
Uncovering the psychoactivity of a cannabinoid from liverworts associated with a legal high
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution-NonCommercial 4.0 International
dc.date.published
2018-10-24
ethz.journal.title
Science Advances
ethz.journal.volume
4
en_US
ethz.journal.issue
10
en_US
ethz.journal.abbreviated
Sci Adv
ethz.pages.start
eaat2166
en_US
ethz.size
11 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
Washington, DC
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02020 - Dep. Chemie und Angewandte Biowiss. / Dep. of Chemistry and Applied Biosc.::02514 - Laboratorium für Organische Chemie / Laboratory of Organic Chemistry::03511 - Carreira, Erick M. / Carreira, Erick M.
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02020 - Dep. Chemie und Angewandte Biowiss. / Dep. of Chemistry and Applied Biosc.::02514 - Laboratorium für Organische Chemie / Laboratory of Organic Chemistry::03511 - Carreira, Erick M. / Carreira, Erick M.
ethz.date.deposited
2018-11-09T05:51:24Z
ethz.source
SCOPUS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2019-01-03T12:47:33Z
ethz.rosetta.lastUpdated
2021-02-15T02:58:10Z
ethz.rosetta.versionExported
true
ethz.COinS
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