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Pea
Published in Sahar Swidan, Matthew Bennett, Advanced Therapeutics in Pain Medicine, 2020
Many of the receptors, channels, and cytokines that PEA interacts with are involved in inflammatory pain signaling (e.g., PPAR-α), immune systems (e.g., GPR55), and endocrine systems (e.g., GPR119). As discussed by Skaper et al.,1 inflammation is a protective response in the human body that is initiated during the cellular healing process. However, when inflammation is prolonged it can cause damage and lead to pain, neurologic diseases, and other inflammatory disorders. Palmitoylethanolamide accomplishes its anti-inflammatory and anti-nociceptive effects by binding to and modulating PPAR-α, which is a regulator of the gene networks controlling pain and inflammation. This gene network switches NF-κB off, which is involved in the pathology of peripheral neuropathies, carpal tunnel syndrome, sciatic pain, osteoarthritis, low-back pain, dental pain, multiple sclerosis, chronic pelvic pain, postherpetic neuralgia, and vaginal pain.5 The cannabinoid-like receptors GPR55 and GPR119 have been linked to inflammation in the gut related to immune system modulation and GLP-1 secretion from entero-endocrine cells, respectively.6 Additionally, PEA influences potassium channels involved in pain perception and desensitizes the TRPV1 channel on sensory neurons. These pharmacodynamic relationships are what gives PEA its anti-inflammatory, immune-modulatory, and anti-nociceptive properties.
Hemp Oil in the Management of Pain, Inflammation, & Stress *
Published in Betty Wedman-St Louis, Cannabis as Medicine, 2019
Research is beginning to look beyond the classical CB1 and CB2 receptors as potential mediators of some of the beneficial effects of phytocannabinoids. Other receptors targeted by phytocannabinoids include G-protein coupled receptors (GP—CRs: GPR18, GPR55, and GPR119). Both GPR18 and GPR55 may recognize the phytocannabinoid CBD. Evidence indicates this phytocannabinoid serves as a GPR55 antagonist, as well as a weak partial agonist.1 GPR18 is expressed primarily in immune cells, while GPR55 is expressed in several brain regions as well as in the dorsal root ganglia in neurons with larger diameters, the hippocampus, frontal cortex, cerebellum, striatum, and hypothalamus. GPR55 may also be expressed in the immune system as well as in the microglia and bone.1
Clinical rationale for CBD in cardiovascular, brain, and liver function and optimal aging
Published in Betty Wedman-St. Louis, Cannabis, 2018
Studies have shown that cannabidiol directly activates 5-HT1A and TRPV, while other research indicates CBD functions as an antagonist by blocking/deactivating G-protein receptor GPR 55 found in the brain cerebellum. GPR 55 modulates blood pressure, bone density, and cancer cell proliferation [17,18].
Emerging drugs for the treatment of bladder storage dysfunction
Published in Expert Opinion on Emerging Drugs, 2022
The cannabinoid (CB) receptors, their endogenous ligands and related enzymes for biosynthesis and degradation constitutes the endocannabinoid system [22,83,84]. From the cannabis plant cannabinoids (phytocannabinoids) can be extracted. The main compounds in such extracts are THC, cannabidiol, and cannabinol. Two G-protein-coupled CB receptors have been defined: type 1 (CB1) and type 2 (CB2). The G-protein-coupled receptor 55 (GPR55), has been described as a third CB receptor, but its pharmacology is incompletely known. Endocannabinoids and ‘exocannabinoids,’ such as phyto-cannabinoids and synthetic cannabinoids, interact with these receptors and some associated endogenous fatty acid amides (FAA). Within the endocannabinoid system at least two major arachidonate-derived ligands, anandamide, and 2-arachidonoylglycerol (2-AG), mediate their effects by binding to CB1 and CB2 receptors. Both anandamide and 2-AG act extensively in the central and peripheral nervous system. They affect not only LUT function but may influence pain, mood, feeding behavior, motivation, and inflammation [85–87].
The potential role of cannabinoids in dermatology
Published in Journal of Dermatological Treatment, 2020
Tabrez Sheriff, Matthew J. Lin, Danielle Dubin, Hooman Khorasani
Beyond the endocannabinoid system, exist novel cannabinoid receptors known collectively as the non-CB1/CB2 receptors or orphan receptors (11,12). Their definitive nomenclature and exact role in skin disease is yet to be classified however they have been identified as targets for cannabinoids. Novel cannabinoids are also G-protein coupled receptors (GPCR) and over the last few years two important receptors have been identified—GPR55 and GPR18. Expression of GPR18 is concentrated in the testis, spleen, peripheral blood leucocytes, and lymph nodes (11,12). Activation of GPR18 by N-arachidonoylglycine (a metabolite of the endocannabinoid anandamide) leads to apoptosis of inflammatory leucocytes thereby dampening local inflammation (13). GPR55 is expressed in the central nervous system and is activated by plant cannabinoids delta-THC and endocannabinoids (anandamide and 2-AG) (12). It has been identified as a possible target for the treatment of inflammation, pain, and Parkinson’s disease (12).
Cannabinoids and bone regeneration
Published in Drug Metabolism Reviews, 2019
Dragos Apostu, Ondine Lucaciu, Alexandru Mester, Horea Benea, Daniel Oltean-Dan, Florin Onisor, Mihaela Baciut, Simion Bran
GPR55 receptor, considered to be the third cannabinoid receptor, is found in central nervous system, intestines, pancreas, liver, prostate, spleen and bone (Idris 2012). At bone level, it is found in human osteoblast and osteoclasts (Whyte et al. 2009; Idris 2012). Most current data are related to its action on osteoclasts, where it regulates differentiation and activity (Whyte et al. 2009). Activation of GPR55 decreases osteoclasts formation but increase their function (Whyte et al. 2009). Animal studies showed a reduced bone resorption process, with no influence on osteoblasts (Whyte et al. 2009; Idris 2010; Sophocleous et al. 2011). GPR55-deficient animal model did not show any significant modification in bone tissue. But GPR55 receptor’s importance in bone metabolism is still under research.