Pharmacological Properties, Therapeutic Potential and Molecular Mechanisms of JWH133, a CB2 Receptor-Selective Agonist

Abstract

The endocannabinoid system has attracted attention as a pharmacological target for several pathological conditions. Cannabinoid (CB2)-selective agonists have been the focus of pharmacological studies because modulation of the CB2 receptor (CB2R) can be useful in the treatment of pain, inflammation, arthritis, addiction, and cancer among other possible therapeutic applications while circumventing CNS-related adverse effects. Increasing number of evidences from different independent preclinical studies have suggested new perspectives on the involvement of CB2R signaling in inflammation, infection and immunity, thus play important role in cancer, cardiovascular, renal, hepatic and metabolic diseases. JWH133 is a synthetic agonist with high CB2R selectivity and showed to exert CB2R mediated antioxidant, anti-inflammatory, anticancer, cardioprotective, hepatoprotective, gastroprotective, nephroprotective, and immunomodulatory activities. Cumulative evidences suggest that JWH133 protects against hepatic injury, renal injury, cardiotoxicity, fibrosis, rheumatoid arthritis, and cancer as well as against oxidative damage and inflammation, inhibits fibrosis and apoptosis, and acts as an immunosuppressant. This review provides a comprehensive overview of the polypharmacological properties and therapeutic potential of JWH133. This review also presents molecular mechanism and signaling pathways of JWH133 under various pathological conditions except neurological diseases. Based on the available data, this review proposes the possibilities of developing JWH133 as a promising therapeutic agent; however, further safety and toxicity studies in preclinical studies and clinical trials in humans are warranted.

Cannabinoid receptor activation potential of the next generation, generic ban evading OXIZID synthetic cannabinoid receptor agonists

“…21,22 As CB 2 -selective agonists are believed to be devoid of the undesirable side effects correlated with CB 1 activation and, importantly, are not believed to be psychoactive, they are considered to be potentially interesting therapeutic tools. [23][24][25][26] It is in this context that the CB 2 agonist MDA-19 (BZO-HEXOXIZID) was developed in 2008 and was later pharmacologically characterized at the University of Texas M.D. Anderson Cancer Center.…”

Effect of Delta-9-tetrahydrocannabinol and cannabidiol on milk proteins and lipid levels in HC11 cells

“…Next, we assessed whether co-treatment of HC11 cells with THC AM630, a synthetic antagonist of CB2 [ 44 ], would reverse the impact of THC on mRNA levels of CSN2 , HK2 and FABP4 in HC11 cells ( Fig 7A–7C ). In addition, we investigated whether co-treatment of HC11 cells with CBD and JWH133, a potent selective CB2 agonist [ 45 ], will reverse the impact of CBD on mRNA levels of CSN2 , HK2 and FABP4 ( Fig 7D–7F ). As DMSO is the vehicle for AM630 and JWH133, a set of HC11 cells were differentiated with 0.1% DMSO, as an additional vehicle control.…”

The Role of Cannabinoid Type 2 Receptors in Parkinson’s Disease

“…One of the major obstacles is that, since CB2 receptors are largely expressed in peripheral organs, in particular in the immune system, CB2 receptor ligands could have some side effects, including immunosuppression [ 34 , 48 ]. In addition, a significant obstacle to the translation from animal models to humans could be that the regulation of CB2 receptors could be different across different species [ 88 , 89 ]. Furthermore, inadequate attention to the nuances of CB2 receptor pharmacology could be another potential reason [ 89 ].…”