The Non-psychotropic Phytocannabinoids Cannabigerol and Tetrahydrocannabinolic Acid Inhibit Rheumatoid Arthritis Synovial Fibroblast Function by Targeting the Wasabi Receptor TRPA1

Torsten Lowin¹, Matthias Schneider² and Georg Pongratz³, ¹Department of Rheumatology and Hiller Research Unit Rheumatology, Heinrich Heine University, Duesseldorf, Germany, Düsseldorf, Germany, ²Department of Rheumatology and Hiller Research Unit Rheumatology, Heinrich Heine University, Duesseldorf, Germany, Duesseldorf, Germany, ³Department of Rheumatology and Hiller Research Unit Rheumatology, Heinrich Heine University, Duesseldorf, Germany, D�sseldorf, Germany

Meeting: ACR Convergence 2020

Keywords: Cell Death, cytokines, Fibroblasts, Synovial, immunology, rheumatoid arthritis

Session Information

Date: Monday, November 9, 2020

Title: Cytokines & Cell Trafficking Poster

Session Type: Poster Session D

Session Time: 9:00AM-11:00AM

Background/Purpose: While medical cannabis is available for german patients since 2017, its use to alleviate symptoms of rheumatic diseases is not recommended due to a lack of clinical studies. While cannabis might be beneficial to treat neuropathic pain, the impact on inflammation has not been assessed adequately. In this study, we investigated the effects of the two non-psychotropic plant cannabinoids, cannabigerol (CBG) and tetrahydrocannabinolic acid (THCA) on the function of rheumatoid arthritis synovial fibroblasts (RASF).

Methods: RASF were treated with THCA and CBG together with TNF or vehicle. After three days, proliferation and cytokine production (IL-6, IL-8 and MMP-3) were assessed. Furthermore, intracellular calcium mobilization and cell death were investigated.

Results: CBG and THCA decreased the proliferation of RASF in vitro (p< 0.001), which was dependent on concentration of cannabinoids and fetal calf serum content of the culture medium. This was accompanied by reduced production of IL-6, IL-8 and MMP-3 (p< 0.001). CBG and THCA increased intracellular calcium (p< 0.001) levels and the uptake of the viability dye PoPo3 (p< 0.001), which was inhibited by antagonizing the wasabi receptor TRPA1 (transient receptor potential type ankyrin). In addition, we observed significant cell death in response to THCA and CBG, which was inhibited by the mitochondrial transition pore inhibitor cyclosporin A. In contrast to TNF pre-stimulated RASF, the effects of CBG and THCA on cytokine production, proliferation, cell death and calcium mobilization were absent or less pronounced in unstimulated RASF.

Conclusion: CBG and THCA showed robust anti-inflammatory effects preferentially in TNF-activated RASF by targeting the wasabi receptor TRPA1. This ion channel might be a novel therapeutic target since it exerts a crucial influence on the function of RASF, which, in vivo contribute to the pro-inflammatory environment in the rheumatoid joint.

Disclosure: T. Lowin, None; M. Schneider, GSK, UCB, Abbvie, 2, Abbvie, Alexion, Astra Zeneca, BMS, Boehringer Ingelheim, Gilead, Lilly, Sanofi, UCB, 5, Abbvie, Astra Zeneca, BMS, Chugai, GSK, Lilly, Pfizer, Sanofi, 8; G. Pongratz, None.

To cite this abstract in AMA style:

Lowin T, Schneider M, Pongratz G. The Non-psychotropic Phytocannabinoids Cannabigerol and Tetrahydrocannabinolic Acid Inhibit Rheumatoid Arthritis Synovial Fibroblast Function by Targeting the Wasabi Receptor TRPA1 [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/the-non-psychotropic-phytocannabinoids-cannabigerol-and-tetrahydrocannabinolic-acid-inhibit-rheumatoid-arthritis-synovial-fibroblast-function-by-targeting-the-wasabi-receptor-trpa1/. Accessed .

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