A new study published in Nature sought to explore the mechanism through which CBD can ameliorate symptoms of conditions that cause inflammation, namely arthritis.
The anti-inflammatory effects of CBD have previously been documented in the scientific literature. As a result, CBD has begun to be used in medical settings to manage symptoms caused by inflammation. However, the exact mechanism through which CBD exerts its therapeutic effects has remained a mystery until now.
Researchers in this study examined the effects of inflammation at a cellular level. This was achieved by mimicking the human inflammatory response within a laboratory setting. Honing in on this response allowed them to discover how CBD exerts its anti-inflammatory effects.
To simulate the effects of inflammation, researchers activated a protein ion channel involved in the pain response. This protein, “transient receptor potential ankyrin (TRPA1),” is of clinical significance because of the targeting of its receptors by acetaminophen, a common over the counter pain-reliever. Mutations in TRPA1 have been linked to pain syndromes and disorders of increased sensitivity. Previous studies have demonstrated the binding of CBD to TRPA1 and its variants.
To learn about the unique inflammatory process of rheumatoid arthritis, inflammatory cells specific to this condition were targeted, called “rheumatoid arthritis synovial fibroblasts (RASF).”
Other mediators important in the inflammatory process were identified, allowing authors to observe how CBD acted upon these players.
Researchers found that CBD reduces both the proliferation of RASF and the overall ability of these cells to survive within their environment, i.e., “cell viability.” It did this, in part, through the activation of TRPA1. This activation diminished the ability for interleukins and matrix metalloproteinases, cells involved in the inflammatory response, to produce RASF.
CBD was also found to reduce cell viability by altering the balance of calcium within the cell’s mitochondria. The increase in mitochondrial calcium allowed for the opening of the mitochondrial permeability transition pore (mPTP), a protein located inside the mitochondria, that when activated, can trigger cell death.
In further exploring the relationship between CBD and RASF, authors noted that the anti-inflammatory effect was emphasized even more when dealing with samples of tissue that had been pre-treated with tumor necrosis factor, or “TNF.”
TNF, a type of inflammatory cell integral to the development of rheumatoid arthritis, is currently targeted in the long-term treatment of the disease. The heightened anti-inflammatory effect seen in the presence of pre-treated TNF is of particular significance. Based on this observation, the authors suggested that CBD may preferentially target RASF in a proinflammatory state.
The researchers proposed a mechanism of action by which CBD exerts its anti-inflammatory effects from the data gathered. They suggested that TNF, with its inflammatory effects, enhances TRPA1, thereby allowing RASF to become vulnerable to CBD’s actions.
CBD binds to TRPA1 and several mitochondrial proteins to alter the calcium balance, which consequently triggers activation of mPTP, leading to cell death.
This study’s implications include the possibility for CBD to be included as a treatment option alongside current, clinically prescribed drugs for rheumatoid arthritis. It is important to understand CBD’s mechanism of action to determine all of its potential applications. Notably, the ability for CBD to not only act as an adjunctive drug but as one that could enhance the effects of existing drugs used for chronic inflammatory diseases like rheumatoid arthritis.
This article was edited and reviewed for medical accuracy by Emma Green, PhD.