Major Phytocannabinoids and Their Related Compounds: Should We Only Search for Drugs That Act on Cannabinoid Receptors?

Abstract

The most important discoveries in pharmacology, such as certain classes of analgesics or chemotherapeutics, started from natural extracts which have been found to have effects in traditional medicine. Cannabis, traditionally used in Asia for the treatment of pain, nausea, spasms, sleep, depression, and low appetite, is still a good candidate for the development of new compounds. If initially all attention was directed to the endocannabinoid system, recent studies suggest that many of the clinically proven effects are based on an intrinsic chain of mechanisms that do not necessarily involve only cannabinoid receptors. Recent research has shown that major phytocannabinoids and their derivatives also interact with non-cannabinoid receptors such as vanilloid receptor 1, transient receptor ankyrin 1 potential, peroxisome proliferator-activated receptor-gamma or glitazone receptor, G55 protein-coupled receptor, and nuclear receptor, producing pharmacological effects in diseases such as Alzheimer’s, epilepsy, depression, neuropathic pain, cancer, and diabetes. Nonetheless, further studies are needed to elucidate the precise mechanisms of these compounds. Structure modulation of phytocannabinoids, in order to improve pharmacological effects, should not be limited to the exploration of cannabinoid receptors, and it should target other courses of action discovered through recent research.

In Vitro and Clinical Evaluation of Cannabigerol (CBG) Produced via Yeast Biosynthesis: A Cannabinoid with a Broad Range of Anti-Inflammatory and Skin Health-Boosting Properties

“…Dermal fibroblasts treated with CBD activate PPARγ and decrease nuclear factor kappa B (NF-kB) levels [53]. In silico studies identified CBG as a PPARα/γ dual agonist [54], and a quinone derivative of CBG has also been suggested to modulate PPARγ [55]. Future research could examine if CBG activates PPARγ and PPARα in dermal cells given their key function in epidermal biology.…”

Role of Cannabidiol and Tetrahydrocannabivarin on Paclitaxel-induced neuropathic pain in rodents

“…Several studies have demonstrated that cannabinoids effectively alleviate neuropathic, in ammatory and cancer-related pain [9]. CBD and THCV are major phytocannabinoids that have received signi cant attention as therapeutic agents in various applications (e.g., anxiety, aging, obesity, cancer, pain, and other CNS diseases) [10]. Unlike THC, which is psychoactive and acts as an agonist at both the CB1 and CB2 receptors, THCV is a non-psychoactive, neutral CB1 antagonist/reverse agonist that can behave as a partial agonist or antagonist at the CB2 receptors depending on the dose.…”

Is It Time to Test the Antiseizure Potential of Palmitoylethanolamide in Human Studies? A Systematic Review of Preclinical Evidence

“…Research studies on its therapeutic properties indicate that CBD is a negative allosteric modulator of cannabinoid (CB) receptors [ 26 ] and may modulate endogenous endocannabinoid (eCB) levels by indirect mechanisms involving the nuclear receptor peroxisome proliferator-activated receptor-α (PPAR-α) and PPAR-α-independent pathways, such as Transient Receptor Potential Vanilloid 1 (TRPV1) and G55 protein-coupled receptor (GPR55) [ 27 ]. Consistent with this, recent research highlighted the importance of widening the investigation to cannabinoid-related compounds whose actions depend on the interaction with non-CB receptors [ 28 ]. Overall, this review demonstrated that PEA, a naturally occurring N-acylethanolamine whose biological effects are related to indirect activation of CB1 receptors as well as PPAR-α and TRPV1 modulation [ 8 , 19 ], may be involved in seizures and epilepsy.…”