Exploration of the lesser-known cannabinoids of Cannabis sativa

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The endocannabinoid system is broadly composed of endogenous cannabinoids; type 1 cannabinoid receptor (CB1R), type 2 cannabinoid receptor (CB2R), GPR18, GPR55, GPR119, and transient receptor potential cation channel subfamily V 1 (TRPV1), and multiple enzymes. The endocannabinoid system can be altered by plant-derived cannabinoids from Cannabis (marijuana) (a.k.a phytocannabinoids). The most well-known phytocannabinoids are d9-terahydrocannabinol (THC) and cannabidiol (CBD). Both THC and CBD are being intensively studied for their potential to treat chronic and acute pain, epilepsy, anxiety, and modulating appetite, among other effects. The pharmacology of THC is relatively well-established: THC is a CB1R and CB2R partial agonist and a GPR18 and GPR55 full agonist. The pharmacology of CBD is far-less clear. CBD has been described as a CB1R negative allosteric modulator, CB2R partial agonist, GPR18 agonist, and GPR55 antagonist, among other effects. Beyond THC and CBD there are at least 90 other phytocannabinoids found in marijuana. Examples of these lesser-known phytocannabinoids include tetrahydrocannabidiolic acid, tetrahydrocannabivarin (THCV), cannabigerol, cannabichromene, and cannabivarin (CBDV). Although some studies have already been conducted to demonstrate the potential medical value of a subset of these compounds - such as THCV and CBDV - in treating conditions such as epilepsy, the biology and receptor-mediated mechanism of action for most of these phytocannabinoids is unknown. The goal of this grant is to work in collaboration with CanniMed Therapeutics Inc. to isolate these lesser-known phytocannabinoids and discover their mechanism(s) of action. At a time when research is increasingly focused on the medicinal capabilities of Cannabis, this research offers a critical means of determining how the lesser-known cannabinoids, that is other than THC and CBD, affect cellular biology. This work will contribute to our understanding of how Cannabis affects the body in order to inform policy, harms reduction, and health choices.