Rheumatoid Arthritis: A Target for Cannabinoids
By Stacey Marie Kerr MD, Hawaiian Ethos Medical Director
The body turning on itself
Rheumatoid Arthritis (RA) can be painful, disfiguring, and difficult to manage. In rheumatoid arthritis, the immune system, which usually protects the body by attacking viruses and bacteria, instead attacks the patient’s own joints. The attack creates inflammation that leads to swelling, pain, and destruction.
the immune system gone awry
About 1.5 million people in the US have rheumatoid arthritis (RA), three-fourths of them women.  It most commonly attacks the hands, feet, wrists, elbows, knees and ankles. The resulting inflammation affects other parts of the body as well, including the heart and the lungs, so it is considered a systemic (whole body) disease.
First, the immune system attacks by sending inflammatory cells into the lining of the joints, and these cells form a layer of abnormal tissue that is thick and fibrous. The joint lining in healthy joints is usually very thin and full of lubricants, so this replacement made of non-lubricated fiber is painful. Inflammation brings in new blood vessels as well, feeding the whole inflammatory process like a tumor that invades and erodes the surrounding cartilage and bone. This painful invasion of inflammatory tissue destroys healthy joints and replaces it with inflamed scar tissue.
We do not know why the immune system goes awry like this, but there is probably a combination of genetic, hormonal, and environmental factors involved.
Joint damage from RA is permanent, so early diagnosis and management are crucial. Symptoms that may alert a patient or physician to the diagnosis are sometimes surprising since many assume the disease will simply show up as localized joint pain.
diagnosis and symptoms
To diagnose RA, a physician will take a medical history, do a physical exam, and then may request imaging studies and blood work. The blood work will test for inflammatory markers that provide clues to the final diagnosis.
Symptoms of Rheumatoid Arthritis 
Symptoms come and go, flaring for days or months then disappearing again.
- Joint pain, tenderness, swelling or stiffness for six weeks or longer
- Morning stiffness for 30 minutes or longer
- More than one joint is affected
- Small joints (wrists, certain joints of the hands and feet) are affected
- The same joints on both sides of the body are affected
- Loss of appetite
- Low-grade fever
If RA is allowed to continue without treatment, the unchecked inflammation leads to other symptoms that can affect the rest of the body.
Symptoms of Untreated Chronic Inflammation 
- Eyes: Dryness, pain, redness, sensitivity to light and impaired vision
- Mouth: Dryness and gum irritation or infection
- Skin: Rheumatoid nodules – small lumps under the skin over bony areas
- Lungs: Inflammation and scarring that can lead to shortness of breath
- Blood Vessels: Inflammation of blood vessels that can lead to damage in the nerves, skin and other organs
- Blood: Anemia, a lower than normal number of red blood cells
The earlier RA is diagnosed, and the earlier treatment is started, the better it is for the patient. Currently, there are drugs used to treat symptoms, and drugs to slow the progression of disease that causes destruction of joints.
conventional treatments: efficacy and side effects
A wide range of pharmaceutical drugs has been developed for the treatment of rheumatoid arthritis. Options include:
Anti-inflammatory medications (NSAIDs) like ibuprofen and Voltaren Gel can ease pain when taken orally or applied topically to affected joints.
Oral steroids are potent and rapid-acting anti-inflammatories and can be used for rapid relief while waiting for NSAIDs to take effect.
Disease Modifying Anti-Rheumatic Drugs (DMARDs) can slow disease progression. These drugs can affect both the inflammatory damage and the immune system’s inappropriate activity. Medications in this class include pills, injectables, and infusions, like Plaquenil, methotrexate and others. All can have significant side effects.
The list of possible side effects for RA drugs is long and somewhat serious, but patients usually tolerate their medications well and get great benefit. Still, patients taking DMARDs must be watchful and monitored to manage therapy safely.
Trying to control the inflammatory and immune system can cause significant problems with other body systems, and so researchers continue to work on safer drugs. Some researchers are looking towards cannabinoids as allies in the fight against RA.
endocannabinoids and phytocannabinoids
Endocannabinoids, made naturally within the human body, modulate inflammation and the immune system as part of maintaining a healthy and balanced homeostasis.  They also act as anti-inflammatories without the NSAID risk of stomach pain and heartburn.
Now that we know about the endocannabinoids’ helpful functions in regards to the immune system and managing inflammation, scientists are investigating phytocannabinoids (compounds found in the cannabis plant) in ongoing efforts to treat RA. 
Like endocannabinoids, phytocannabinoids can be effective anti-inflammatories, acting through a different mechanism than NSAIDs.  They also help modulate a dysfunctional immune system.  Both pre-clinical and human studies are being done to learn about how cannabis helps, and about specific cannabinoids that can be used in RA. [3, 5]
Success in a human trial
Cannabis has been used throughout history to treat the pain that comes with rheumatoid arthritis.  Recent studies show that THC has pain reducing qualities, and both THC and CBD have anti-inflammatory effects. [4, 6] In many animal models, CBD has been found to block progression of RA. 
A human trial on cannabis that included 58 individuals with RA compared the use of a 1:1 ratio of CBD:THC and a placebo. This ratio of phytocannabinoids was chosen to reflect cannabis historically used as medicine and to take full advantage of the synergy between THC and CBD. 
There were some minor cannabinoids present in the medicine as well – all of which have been found to have anti-inflammatory properties. Consideration was given to the 'entourage effect' whereby the whole plant is more effective than isolated parts. [3, 7]
Researchers found that the patients using cannabis-based medicine had statistically significant improvements in pain on movement, pain at rest, quality of sleep, inflammation and intensity of pain. 
They also concluded that, "The element that can cause the 'high' in cannabis, THC, has valuable pharmacological activity. It is thought to be an essential therapeutic component and therefore it can't be removed from the medicine.” Balanced with the other cannabinoids, THC was tolerated well because despite including THC in the mix, there were no adverse-effect withdrawals or serious side effects among the participants. 
from the plant to the lab, then back to the plant?
Work is being done in labs on synthetic cannabinoids to treat rheumatoid arthritis, and there is encouraging progress being made.
Working with synthetics provides a better understanding of the mechanisms of action and the sites of activity, which is encouraging more research in this field. But the benefits of medicine made from the whole plant should not be denied – the entourage effect noted in cannabis keeps proving that the sum is more effective than any of the individual parts. 
Those who wish to use cannabis to help manage their rheumatoid arthritis should work with their rheumatologist to find the best, and the safest, medicine available to manage the destructive effects and progression of disease.
Using cannabis together with pharmaceuticals may provide the best of both worlds. A balanced blend of THC and CBD used regularly along with disease specific prescriptions could provide more comfort and less destruction of joints and other tissues.
2. Tanasescu R and Constantinescu CS. Cannabinoids and the Immune System: An Overview, Immunobiology 215(2010)588–597
3. Blake, et al, Preliminary assessment of the efficacy, tolerability and safety of a cannabis-based medicine (Sativex) in the treatment of pain caused by rheumatoid arthritis, Rheumatology 2006;45:50–52. doi:10.1093/rheumatology/kei183
4. Nagarkatti P et al. Cannabinoids as novel anti-inflammatory drugs. Future Med Chem. 2009 October; 1(7): 1333–1349. doi:10.4155/fmc.09.93.
5. Richardson D et al. Characterisation of the cannabinoid receptor system in synovial tissue and fluid in patients with osteoarthritis and rheumatoid arthritis, Arthritis Research & Therapy 2008, 10:R43 (doi:10.1186/ar2401)
6. Hill, et al. Cannabis and Pain: A Clinical Review Cannabis and Cannabinoid Research 2017, 2.1, http://online.liebertpub.com/doi/10.1089/can.2017.0017
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