Why Wairuakohu?

Perrottetinene Discovery

In 1994 Japanese researcher Yoshinoiu Asakawa and co-workers reported the discovery of a bibenzyl monoterpene, which they named perrottetinen (later called perrottetinene, referred to as PET here, structure 1 below) (Toyota et al. 1994). This discovery came from a Japanese collection of the liverwort Radula perrottetii. The Japanese paper pointed out the structural similarity of PET to tetrahydrocannabinol (THC), the psychoactive substance found in Cannabis sativa.

The confirmation that PET is indeed a psychoactive cannabinoid did not come until 2018. A paper from a group of Swiss researchers (who we are now working with) demonstrated that chemically synthesised PET readily penetrated the brain and induced hypothermia, catalepsy, hypolocomotion, and analgesia in a CB1 receptor–dependent manner in mice (Chicca et al. 2018).

“Cullmann and Becker (1999) identified PET in Radula laxiramea from Costa Rica.” Another study published in 2020 reports PET in two other species collected in Japan (Asakawa et al. 2020). We have not found any other reports of PET from natural sources.

Wairuakohu Research

“The Asakawa group’s report of PET in Radula marginata collected from the Waitakere Ranges (Toyota et al. 2002) sparked interest in Aotearoa New Zealand.” “Researchers collected Radula marginata (Herbarium specimen No. YM2; dry wt. 4g) in May 2001 at Waitakere Range, Auckland, New Zealand. They deposited voucher specimens at the Faculty of Pharmaceutical Sciences, Tokushima Bunri University, and Plant Systematics, School of Biological Sciences, University of Auckland. The record does not indicate permission to collect or consultation with Māori. Dr. Matt Renner and Dr. John Braggins, both affiliated with the School of Biological Sciences, University of Auckland at the time, contributed as co-authors.”

Introduction to Perrottetinenic Acid (PETA)

Toyota et al. (1994) reported Perrottetinenic acid (referred to as PETA here, structure 2), a potential biosynthetic precursor of PET, from this collection. “Researchers reported higher amounts of related bibenzyl derivatives, especially compound 4.” We have not found any other reports of PETA from natural sources (Chemical Abstracts search, 18 February 2021).
The Asakawa group has since reported on an unidentified New Zealand Radula species (from South Westland, Te Wai Pounamu) which yielded monoprenyl bibenzyl (compound 4), but not PET (Nagashima et al. 2006).

Māori Consultation

In 2016 a German group, led by Prof Oliver Kayser at Dortmund Technical University, reported on “Biocontrol potential of endophytes harbored in Radula marginata (liverwort) from the New Zealand ecosystem” (Kusari et al. 2014). “We did not record any Māori consultation. Additionally, we are very thankful to the Auckland Council and the New Zealand Government for allowing us to bioprospect Radula plants. No analysis of PET content was reported.”

Research Team and Collaboration

In 2018 Oliver Kayser and his PhD student, together with researchers from Plant & Food Research (PFR), Blue Plunkett and Richard Espley, reported on “Identification of Putative Precursor Genes for the Biosynthesis of Cannabinoid-Like Compound in Radula marginata” (Hussain et al. 2018). For this study, the researchers collected samples for research purposes beside the Mount Donald McLean track, Waitakere Ranges, in February 2016, after obtaining permission from Auckland Regional Council (ARC) in December 2015. Senior Ranger Conservation at ARC, Van Haresnape, confirmed via email to PFR that: ‘I have had a reply from local iwi and they are happy for you to proceed’ (18th December 2015).

Absence of PET Detection in the Study

‘The paper reported on the tentative identification of a number of genes that might lead to the production of PET, although not the final steps in the pathway. “Researchers did not identify PET in this collection. However, they reported geranyl bibenzyl acid (compound 3), a potential biosynthetic precursor of PET. They identified this compound using gas chromatography-mass spectrometry (GC-MS) rather than isolating it and performing detailed nuclear magnetic resonance spectroscopy (NMR), so we consider this identification tentative. Previous studies have reported compound 3 from the higher plant Helichrysum umbraculigerum (Asteraceae), a prolific producer of phytocannabinoids (Pollastro et al. 2017).”