Phytocannabinoids: a unified critical inventory

Abstract

Covering up to January 2016Cannabis sativa L. is a prolific, but not exclusive, producer of a diverse group of isoprenylated resorcinyl polyketides collectively known as phytocannabinoids. The modular nature of the pathways that merge into the phytocannabinoid chemotype translates in differences in the nature of the resorcinyl side-chain and the degree of oligomerization of the isoprenyl residue, making the definition of phytocannabinoid elusive from a structural standpoint. A biogenetic definition is therefore proposed, splitting the phytocannabinoid chemotype into an alkyl- and a β-aralklyl version, and discussing the relationships between phytocannabinoids from different sources (higher plants, liverworts, fungi). The startling diversity of cannabis phytocannabinoids might be, at least in part, the result of non-enzymatic transformations induced by heat, light, and atmospheric oxygen on a limited set of major constituents (CBG, CBD, Δ-THC and CBC and their corresponding acidic versions), whose degradation is detailed to emphasize this possibility. The diversity of metabotropic (cannabinoid receptors), ionotropic (thermos-TRPs), and transcription factors (PPARs) targeted by phytocannabinoids is discussed. The integrated inventory of these compounds and their biological macromolecular end-points highlights the opportunities that phytocannabinoids offer to access desirable drug-like space beyond the one associated to the narcotic target CB.

Individual and combined effects of acute delta-9-tetrahydrocannabinol and cannabidiol on psychotomimetic symptoms and memory function

“…Several factors predict vulnerability, including the rs2494732 locus of the AKT1 genotype 3–5 , adolescent exposure 6,7 , frequency of use 8–10 , schizotypy or schizophrenia 11–15 and the type of cannabis used 2,16 . Although it is typically classified as a single drug, the cannabis plant can contains over 100 unique ‘cannabinoids’, with diverse and sometimes opposing pharmacological actions 17 .…”

Developing Robust Standardised Analytical Procedures for Cannabinoid Quantification: Laying the Foundations for an Emerging Cannabis-Based Pharmaceutical Industry

“…Plants of this genus produce a group of isoprenylated resorcinyl polyketides, also known as cannabinoids [5]. Cannabinoids vary structurally in terms of their isoprenyl residue as well as their resorcinyl alkyl side chain and moiety (Fig.…”

“…1). Nine primary isoprenyl topological arrangements or “types” of cannabinoids occur in planta [5]. The resorcinyl alkyl residue can also vary by carbon number [6].…”

“…More than 100 cannabinoids have been identified from Cannabis [1, 8]. While impressive, this catalogue does not necessarily reflect the metabolic capacity of this genus but may be a consequence of oxidative instability of plant-derived cannabinoids, causing a range of degradation products to occur after synthesis [5]. …”

Medical cannabis in the treatment of cancer pain and spastic conditions and options of drug delivery in clinical practice

“…Naturally occurring phytochemicals of the species Cannabis sativa, Cannabis indica and Cannabis ruderalis comprise nearly 1,300 chemical entities. Of these, more than 140 are classified as phytocannabinoids 11 substances able to bind to cannabinoid receptors. These compounds are present in the highest amounts in the viscous resin produced by the glandules of female cannabis inflorescence 12 .…”