By CBD Study on Inflammation
Cannabis sativa contains a phytocannabinoid called cannabidiol (CBD), which is non-intoxicating and has anti-inflammatory benefits in several inflammatory conditions, including arthritis. The exact mechanism by which CBD works is uncertain because it binds to numerous receptors and enzymes.
This study found that CBD suppresses IL-6/IL-8/MMP-3 generation, lowers cell viability, and raises intracellular calcium levels in rheumatoid arthritis synovial fibroblasts (RASF). Transient receptor potential ankyrin (TRPA1) was activated in inflammatory circumstances, amplifying these effects, and the mitochondrial permeability transition pore was opened.
Changes in intracellular calcium levels and cell viability were measured using the fluorescent dyes Cal-520/PoPo3 in conjunction with cell titer blue and the luminescent dye RealTime-glo.
The TRPA1 protein was identified using flow cytometry, and the cell-based impedance was measured using the XCELLigence technology. The measurement of cytokine production involved ELISA. CBD reduced the viability, growth, and IL-6/IL-8 production of RASF cells.
Additionally, pretreatment with TNF increased the absorption of the cationic viability dye PoPo3 and intracellular calcium in RASF, which were also augmented by CBD. When coupled with the TRPA1 antagonist A967079, but not with the TRPV1 antagonist capsazepine, CBD’s effects on calcium and PoPo3 absorption were lessened.
Furthermore, the effects of CBD on cell viability and IL-8 production were decreased by the mitochondrial permeability transition pore inhibitor cyclosporin A. Both Decynium-22, an inhibitor of all organic cation transporter isoforms, and DIDS, a voltage-dependent anion-selective channel inhibitor, reduced PoPo3 uptake.
By activating TRPA1 and mitochondrial targets, CBD lowers intracellular calcium levels, reduces cell viability, and prevents RASF IL-6/IL-8/MMP-3 synthesis. This effect was made worse by pretreatment with TNF, proving that CBD selectively targets activated, pro-inflammatory RASF. Due to its ability to target synovial fibroblasts in inflammatory conditions, CBD has an anti-arthritic impact and may reduce the symptoms of arthritis.
Introduction
Cannabidiol (CBD), a non-intoxicating cannabinoid, is present in Cannabis sativa. Tetrahydrocannabinol (THC), the psychoactive component of cannabis, acts directly on cannabinoid receptors 1 and 2 (CB1 and CB2), whereas CBD controls the effects of agonists, suggesting an allosteric function2. Additionally, CBD interacts with the mitochondrial proteins PPAR, GPR3/6/12/18/55, TRPV1/2, TRPA1, 5-hydroxytryptamine receptor, and others. Even at high doses, CBD is well tolerated despite its promiscuous pharmacology.
Humans are susceptible to diarrhea and exhaustion from CBD, and it interacts with other drugs since it slows down the liver’s CYP enzymes’ ability to break down other therapeutic substances. Although infantile epilepsy has been successfully treated with CBD, its effects on inflammation have only been examined in animal models. Animals with osteoarthritis or arthritis brought on by collagen respond favorably to CBD’s anti-inflammatory and analgesic effects, but the mechanism of action is unknown.
In this investigation, we examine how CBD impacts synovial fibroblasts from patients with rheumatoid arthritis in terms of intracellular calcium, cell survival, and cytokine production (RASF). RASFs have a crucial role in joint degeneration in RA20 because they emit pro-inflammatory cytokines and matrix-degrading enzymes. In fact, subsets of RASF preferentially mediate inflammatory response or joint degradation, underlining their significance in the genesis of RA21.
