Improving Treatment Efficacy for Rheumatoid Arthritis (RA)
This is a huge topic, and the chances are this one probably hits home, affecting either you or a loved one. This is because Rheumatoid Arthritis (RA) affects 18 million people worldwide, so many of us are very familiar with it (1). (RA) is an immune mediated inflammatory disease characterized by systemic inflammation that primarily affects joints (pain & swelling) initially, but this autoimmune disease eventually progresses to damage our heart, kidneys, eyes, skin, lungs, and nervous system (1, 2). RA involves many kinds of cells including osteoclasts, B-cells, T-cells, macrophages, and fibroblastlike synoviocytes (7). RA also involves molecules such as interleukin-1β, tumor necrosis factor-α, interleukin-6, matrix metalloproteinases [MMPs], and chemokines and here is where it gets interesting (7)! To halt the progression of this disease process (RA), we would need to modulate or interact with these cells and molecules directly… This information should hit the front-page news because ALL of these cells and molecules that I just mentioned above have CBD receptors (CB1 and/or CB2) to which we can use this to our advantage to control their activity (7)!
This means that we can use these CB1 and CB2 receptors that are present intracellularly and extracellularly to control the disease progression of RA and in this study, they stated that they are exploring cannabinoid medicine as a potential target for treatment for RA, which they should. We are talking about addressing the root cause of this disease at a cellular level, what an absolute breakthrough in medicine! Scientists wish they could patent a medication that could do the things the endocannabinoid system (ECS) is capable of when interacting with cannabinoids (both exogenous and endogenous). One amazing receptor system created by The Most High. Praise God!
Now here is where I have a problem. There is currently no cure for this autoimmune disease, we are just managing the symptoms of pain, inflammation, swelling, and trying to minimize the body’s own immune system from attacking itself and causing organ damage. Yet there is information like this out since 2015. If our medical system can’t stay up to date with recent research and implement it as a standard more rapidly (almost 10 years after this study, yet they still state no cure), then they need to go back to the drawing board.
While conventional medicine tells us there is no cure for RA and that we must continuously take their medications to mitigate the side effects of RA, I am here to tell you that current research suggests otherwise. On top of conventional medicine being behind on research, they have another fault when addressing RA that I would like to point out. It’s gut health!
You’ve probably heard me say this before (if not, follow us on Instagram HERE), conventional medicine has no understanding of the importance of gut health and this topic of RA is a prime example. Current research correlates a direct link between RA and a damaged mucosal membrane that lines the intestines, leading to what is known as increased intestinal permeability (aka leaky gut).
Current treatment is aimed towards controlling immune response and decreasing inflammation, but this is a faulty approach, especially if there is no regard for gut integrity. To keep it simple, if "leaky gut" has a direct correlation to RA and we are trying to address RA at the root cause, looking at the gut may give us more insight and improve our effectiveness of treatment. Especially when combined with cannabinoid medicine. Simply stating there is no cure for RA is not acceptable and we should never stop there (2). Every thing in the universe has a cause and effect relationship. Instead of saying there is no cure, a better explanation would be they don't know enough about the body or disease process. Regardless, we should never stop looking for answers.
Is there no cure for RA or are they ignoring research to continue to profit off our ill will? Let’s dive deeper into gut health, since it plays an enormous role in the development and progression of RA.
According to Rheumatology, a peer-reviewed open access medical journal, RA patients have altered gut barrier integrity, increasing serum markers of gut permeability, which gives a positive indication that these are associated with RA disease progression (3).
Basically, these proteins called zonulin keep these openings in the intestinal barrier pulled close, kind of like a gatekeeper. When they are not doing their job, they become slack (don’t we all? LoL) and start to let these foreign pathogens through, which then wreaks havoc on our immune system by increasing serum zonulin levels, which is directly correlated with leaky intestinal barrier, gut bacteria imbalance, and inflammation (3).
Current treatment for RA involves disease-modifying antirheumatic drugs (DMARDs) as a treatment for RA. The goal here is to slow down and stop the progression of the disease and prevent joint damage. They use a combination of drugs, a few including (5):
-Methotrexate- slows down the disease progression by interfering with DNA synthesis (what could possibly go wrong here? LoL). Side effects include nausea, fatigue, and raised liver enzymes, which indicates liver damage.
-Leflunomide- inhibits white blood cell migration that contributes to inflammation (what could possibly go wrong here? LoL). Side effects include potential liver damage, GI tract issues (which we may already have a problem here), and hair loss.
-Sulfasalazine- anti-inflammatory effects thought to help modulate immune response. Side effects include rash, liver function abnormality, and GI issues.
-Janus Kinase Inhibitors- interfere with JAK-STAT signaling pathway involved in the inflammatory process. Side effects include risk of infections, elevated liver enzymes indicating liver damage, and blood clots.
Could it be that the side effects of DMARDs outweigh the benefits, especially if there are other treatment options that are backed by science shown to be more safe AND effective? I believe in informed consent and full disclosure of a medication package insert before opting for a treatment plan. That only makes sense, right? After all, we are here to improve humans’ quality of life through proper prevention, diagnoses, and treatment of disease. We want to live healthier, longer lives and feel our best, not trade in our health for a drug that may or may not work (which the study stated their stance on their effectiveness to treat RA by stating there is no cure for RA). Could it be that the side effects from these medications may be potentially worse than the disease itself? Personally, I think proper disclosure of medications, their mechanism of action, and side effects will help us weigh the pros and cons so we can choose a proper treatment option that fits everyone needs and after the full disclosure of DMARDs side effects, I'd say that may not be the answer medical researchers are looking for.
After understanding the role of the endocannabinoid system (ECS) and the importance of gut health on immune system modulation, I am a firm believer that we can use these tools to improve how we address RA in medicine and the studies back that statement.
Recently, cannabinoid medicine has been gaining the spotlight when it comes to autoimmune disease. We already know that CBD and THC combines can offer some amazing pain and inflammation relief for conditions like arthritis, but I want to take this a step further and put some emphasis on these cannabinoids' ability to modulate or control our immune response (6). After all, the goal stays the same when it comes to facing disease, regardless of the medical model. The goal for RA treatment is to slow down and stop the progression of the disease, minimize joint pain/damage, and control an overactive immune system.
Research suggests that cannabinoid medicine shows a promising future when discussing RA. This is mainly due to the effects produced when cannabinoids interact with the ECS and its receptors (CB1 and CB2).
CB2 receptors play an important role in the development of RA and studies show we can use these receptors to mitigate the disease process associated with RA. Activation of CB2 receptors was shown to inhibit the production of antibodies, proinflammatory cytokines, help to inhibit synovial inflammation (what lines the tissues in joint space, causing joint pain), helps to reduce bone erosion (bone cells have CB2 receptors) and strengthen cartilage to protect joints from destruction, hyperplasia (overproduction of cells), and helping to mediate immune response damage caused from T cells (what autoimmune diseases do) (7). When discussing the destructive effects that RA has on the body and immune system, cannabinoid therapy is currently being sought out as a treatment option against inflammatory and autoimmune diseases like RA (6).
One study from 2009 concluded that the ECS is involved in immunoregulation and neuroprotection, controlling immune response on various cells, including the cytokine network (6). We already know that several cytokines are involved in the formation (pathogenesis) of RA, so the ability to modulate or downregulate the cytokine network, in addition to the induction of apoptosis in immune cells, and downregulation of the innate and adaptive immune response gives cannabinoids therapy medical researchers much hope when it comes to RA. (6).
In fact, cannabinoids were also shown to express protective properties for our healthy cells. One study concluded that cannabinoids were able to offer protection for organs from damage from a heightened immune response that is seen with autoimmune diseases. The study stated that cannabinoids helped the liver recover from damage caused from the immune system itself (immune mediated damage), offering liver protecting properties, which is the exact opposite of what DMARDs were shown to do. As stated above, almost every medication on the DMARDs list was shown to induce liver injury. (6).
I have one goal in mind, to improve the treatment options that we have available to patients around the world so we can improve our quality of life, lessen the burden disease causes, and to improve treatment options that we have available. I believe that cannabinoid medicine can do just that. The studies are there showing the potential, it’s just that there is disconnect between these studies and our medical model. I will say that I am glad to see how much medicine has changed in the last 5 years. We now have physicians recommending our canna products to their patients! This is a huge win for the people!
As more studies come out, we can learn more about the true potential of cannabinoid medicine and how we can use it to improve how we face disease and I am excited to play a part in this movement.
One plant with seemingly endless uses, now that’s what I call medicine!
Bee Well,
Brandon Farless
*This information is for educational purposes only and we are simply sharing information pertaining to these studies. No medical advice or claims are being made on my behalf.
References
1. World Health Organization. (2023, June). Rheumatoid arthritis. World Health Organization. https://www.who.
2. Bullock, J., Rizvi, S. A. A., Saleh, A. M., Ahmed, S. S., Do, D. P., Ansari, R. A., & Ahmed, J. (2018). Rheumatoid Arthritis: A Brief Overview of the Treatment. Medical principles and practice : international journal of the Kuwait University, Health Science Centre, 27(6), 501–507. https://doi.org/10.
3. Audo, R., Sanchez, P., Rivière, B., Mielle, J., Tan, J., Lukas, C., Macia, L., Morel, J., & Immediato Daien, C. (2022, August 10). Rheumatoid arthritis is associated with increased gut permeability and bacterial translocation that are reversed by inflammation control. OUP Academic. https://academic.
4. BDMARDs in the management of rheumatoid arthritis. Physiopedia. (n.d.). https://www.physio-
5. Benjamin, O. (2023, July 3). Disease-modifying antirheumatic drugs (DMARD). StatPearls [Internet]. https://www.ncbi.
6. Pandey, R., Mousawy, K., Nagarkatti, M., & Nagarkatti, P. (2009). Endocannabinoids and immune regulation. Pharmacological research, 60(2), 85–92. https://doi.org/10.
7. Gui, H., Tong, Q., Qu, W., Mao, C. M., & Dai, S. M. (2015). The endocannabinoid system and its therapeutic implications in rheumatoid arthritis. International immunopharmacology, 26(1), 86–91. https://doi.org/10.
