Cannabis for Rheumatoid Arthritis?
More research is needed on the benefits and barriers of this alternative treatment
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by Julie Maurer
Contributing Writer, MedPage Today
This Reading Room is a collaboration between MedPage Today® and:
As Illinois has recently become the 11th state to legalize marijuana, we all know that it is just a matter of time before it will take by storm the marketing-sensitive healthcare world. So, aside from heated media debates about the healthcare benefits/faults of marijuana, what do we know about the cannabinoids effects on the human body?
The endocannabinoid system consists of the endogenous cannabinoids (endocannabinoids), cannabinoid receptors, and the enzymes that synthesize and degrade endocannabinoids. The effects of cannabinoids and endocannabinoids are mediated by two G protein‐coupled receptors (GPCRs), CB1 and CB2; these cannabinoid receptors are the most abundant GPCRs. CB1 receptors are present in very high levels in several brain regions and in lower amounts in a more widespread fashion (adipocytes, liver, pancreas, and skeletal muscle), and they mediate many of the psychoactive effects of cannabinoids. CB2 receptors have a similarly ubiquitous but more restricted distribution, being found in a number of immune cells (particularly those derived from macrophages, such as microglia, osteoclasts, and osteoblasts) and neurons. In short, CB1 is more THC-like, and mediates psychogenic and pain effects, while CB2, more like CBD, is playing a role in the immune system.
A large body of science set out to explore the widespread benefits of playing with the CB2 receptor in vivo and mice models, and everything that plagues the human race is the target: cancer, dementia, pain and, of course, auto-immunity. Hundreds of small molecules are being developed in large or small pharmaceutical companies targeting the endocannabinoid receptor, and the stock market is stirring as the laws around marijuana products versus synthetic receptor agonists are rapidly changing.
We, rheumatologists, had already seen a lot of media excitement about drugs with tons of benefits and no side effects, but we now know better. We expect the cannabinoids to deliver immune modulatory benefits, perhaps some pain reduction and improved quality of life, but we are cautious about addictive and other side effects, and we pray that the media’s eagerness to sensationalize does not replace common sense and good science. Which (good science), is slowly, but surely, developing.
With the growing use of cannabis as an alternative treatment for medical conditions, some researchers are curious as to its effect on rheumatoid arthritis (RA) and other rheumatoid diseases.
“The pain associated with rheumatic diseases is considered a prevalent indication for medicinal cannabis in various countries. Thus far, preliminary clinical trials have explored the effects of cannabis on RA, osteoarthritis and fibromyalgia,” wrote Daphna Katz-Talmor, et al. in a review published in Nature Reviews Rheumatology.
Those reviewers determined, however, that more research was needed before any clinical recommendations could be made regarding the use of cannabis.
In 2016, another review appeared in the German publication Der Schmerz, which set out to determine if there was evidence to recommend cannabis for pain management in rheumatology patients.
The researchers, Mary-Ann Fitzcharles and coworkers, combed through the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, www.cannabis-med.org, and clinicaltrials.gov for randomized controlled trials. Their criteria included those that were at least two weeks long and had ten patients or more per treatment arm with herbal cannabis or pharmaceutical cannabinoid products in fibromyalgia syndrome, osteoarthritis, chronic spinal pain, and RA pain. “Outcomes were reduction of pain, sleep problems, fatigue and limitations of quality of life for efficacy, dropout rates due to adverse events for tolerability, and serious adverse events for safety,” Fitzcharles and colleagues wrote.
They only found three studies that fit the bill, and the authors noted the risk of bias was high with all three.
“The findings of a superiority of cannabinoids over controls (placebo, amitriptyline) were not consistent. Cannabinoids were generally well tolerated despite some troublesome side effects and safe during the study duration,” Fitzcharles and the other researchers wrote. “Currently, there is insufficient evidence for recommendation for any cannabinoid preparations for symptom management in patients with chronic pain associated with rheumatic diseases.”
Which is why authors of a May 2019 review published in Current Opinion in Rheumatology believe that studying why cannabinoids might be useful to patients will give physicians a clearer direction.
“Due to their anti-inflammatory effects, (endo-) cannabinoids have been considered as a potential therapy for the treatment of rheumatic diseases. However, at the moment there is no significant evidence for the efficacy of cannabinoid-based drugs in the treatment of RA, although it is included in the list of conditions eligible for receiving medical cannabis in Canada and several US states and the majority of patients with arthritis reported beneficial effects of the drug, for example less pain and an opioid-sparing effect,” Torsten Lowin and colleagues wrote.
The authors noted that many RA therapies can interfere with cytokine production or signaling but can have side effects, including infection and immune disturbances.
“Therefore, reduction of proinflammatory cytokine production and signaling without an overt risk of infection would be a preferable treatment of RA,” Lowin and colleagues wrote. “In vitro data and results from animal experiments suggest that cannabinoids might help with just that.”
The researchers noted that the use of cannabis might not only reduce inflammation and pain, but may also help RA patients with comorbidities, such as depression, hypertension, and osteoporosis.
“Significantly, the consumption of cannabis is also associated with lower risk of metabolic syndrome and diabetes and might therefore prevent the RA-induced changes in metabolism,” Lowin and colleagues wrote.
And, it could help patients respond to their treatment, they found.
“Furthermore, CBD might boost the effect of antirheumatic drugs as it has been shown that it increases the uptake of chemotherapeutic compounds into cancer cells,” the authors wrote.
Marni Groves, MSN, NP-C, an assistant in rheumatology at Vanderbilt Department of Medicine in Nashville, Tenn., said that she does feel cannabinoids can be beneficial to patients with RA to reduce joint pain — especially creams and rubs that contain CBD oil. However, she advises patients to use caution when using these products.
“I have had patients who have utilized CBD and hemp creams, rubs, oils, and candies and they do tell me that they feel like their joint and muscle pains are less and more tolerable,” Groves told MedPage Today in an e-mail.
She noted one barrier for patients is the expense, which may not be affordable for everyone. Groves recommends patients also be careful about the product they are purchasing.
“The true content of the oils, creams, rubs, and candies is not verified because these are not FDA regulated,” she added. “Lastly, these products are not advertised (to say) that using these products might cause a positive drug screen.”
While there are many benefits and barriers to the use of cannabis for RA patients, the common theme in the published reviews is that more research is needed. Regardless, this is not likely a topic that will diminish soon.
The Canadian Rheumatology Association even published a position statement in The Journal of Rheumatology this year on the topic.
“Despite lack of evidence for use of medical cannabis in rheumatology patients, we acknowledge the need to provide empathetic and pragmatic guidance for patient care. This position statement aims to facilitate the dialogue between patients and healthcare professionals in a mutually respectful manner to ensure harm reduction for patients and society,” the association concluded.
More research is needed on the benefits and barriers of this alternative treatment