Demystifying the liverwort Radula marginata, a critical review on its taxonomy, genetics, cannabinoid phytochemistry and pharmacology

Radula marginata Taylor is a subtropical liverwort, endemic to the Northern island of New Zealand in the Pacific region. Despite its significant potential as an alternative source of a THC-like phytocannabinoid, the biosynthesis of this compound remains elusive. Following the discovery of a bibenzyl cis-tetrahydrocannabinol (perrottetinene) in R. marginata, research has focused on genetic fingerprinting and transcriptomic analysis for the genes involved in its biosynthesis. More recently, its pharmacological activity with the endocannabinoid receptors (CB1 and CB2) has been demonstrated, paving the way to more extensive research on this liverwort. Here, we provide an in-depth review of the current research. Firstly, we describe the taxonomy and phytogeography of R. marginata, followed by the symbiosis and evolutionary aspects of bryophytes in general, with a specific focus on liverworts. We then review the physiology and anatomy from scanning electron microscopy data. The presence of the oil bodies and their functional insights for the storage of secondary metabolites, such as perrottetinene, are illustrated. We review the available genetic and transcriptomic resources for R. marginata. We discuss pharmacological aspects of the natural bi-benzyl cis-perrottetinene as compared to THC. The reported partial agonistic activity of this compound at CB1 and CB2 receptors, and the need for further study for the treatment of inflammatory conditions, is considered. Moreover, given that THC has beneficial effects topically, we discuss the potential use of R. marginata for dermatological conditions. Finally, we elaborate on the ethnobotanical aspects and the legal and ethical position of plant collection in New Zealand. Overall, this review gives the first detailed overview of R. marginata. We include the morphology, taxonomy, anatomy, physiology, evolution as well as the genetic basis linking it with electron microscopic studies and its biological effects.