Lack of Cannabis Research is Hampering Arthritis Treatments, Review Finds

Many patients with rheumatic disease pain are aware of the benefits of cannabis-based treatments, but research is lagging behind them.

That is the view of a new review from CreakyJoints, published in Current Rheumatology Reports. This slow progress is largely down to a lack of standardization in clinical research, restrictive state laws, and a significant skew in recent scientific literature towards reviews rather than primary research. CreakyJoints is an international digital community for arthritis patients and caregivers and is a part of the Global Healthy Living Foundation (GHLF).

The authors of this new review from the GHLF and the UCLA Cannabis Research Initiative also include several recommendations and tools for rheumatologists and healthcare providers, so that they can be more able to discuss the benefits and risks of medical cannabis treatment with their patients.

Lack of research is limiting the potential of medical cannabis

In this review, the researchers identified literature on cannabis and rheumatic disease, fibromyalgia, rheumatoid arthritis, and other common rheumatic diseases published between the years 2015 to 2020.

The review considered both pre-clinical and clinical evidence relating to the most common rheumatic conditions and their symptoms. It found that while there was strong preclinical evidence to support the use of medicinal cannabis products in treating the pain and inflammation associated with these conditions, the overall clinical evidence base is still lacking. This is largely down to the “nuanced legal complexities of state vs federal law”, the authors wrote, which have presented significant challenges for American cannabis researchers.

For rheumatoid arthritis (RA), there were numerous strong examples of good quality pre-clinical evidence supporting the use of cannabis-based medicines to treat arthritic inflammation. Endocannabinoid receptors have been found on the synovial fibroblasts (SFs) that are activated in RA and are responsible for much of the inflammation and cartilage destruction associated with the condition. Various mouse models of RA also showed that treatment with synthetic or plant-derived cannabinoids could halt the progression of RA-like joint deformation and inflammation.

But despite this strong pre-clinical evidence, the researchers could only find one small randomized clinical trial studying a cannabis-based treatment for RA. In this trial, treatment with an oromucosal spray containing both THC and CBD resulted in significant improvements in pain during movement and joint function, with only mild adverse events reported compared to the placebo group.

The findings were similar for osteoarthritis; there was strong preclinical evidence but insufficient clinical data to adequately draw any conclusions on medical cannabis treatment for patients. It was also noted that most of the clinical studies done on patients with osteoarthritis were done retrospectively, and so cannot strictly determine causation. The single randomized controlled trial identified in the review was also terminated early for futility.

Based on the current state of the scientific literature, the review authors concluded that more pre-clinical and clinical studies are still needed to fully characterize the effects of cannabis on fibromyalgia and systemic lupus erythematosus.

Interest in cannabis medicines for rheumatism is increasing

Another finding of this review was that, despite such slow research progress, patient interest in using cannabis to treat rheumatic disease pain has continued to increase significantly in recent years. For example, in one survey of rheumatic disease patients highlighted by the review, it was observed that 6.3 percent of respondents in 2014 reported using cannabis. When the same survey was sent out in 2019, the proportion of cannabis-using respondents had almost tripled to 18.4 percent.

CreakyJoints’ own analysis from its patient research registry would also support this conclusion, the review authors added.

“In 2019, CreakyJoints presented data from our ArthritisPower Research Registry study showing more than half of arthritis patients reported wanting information on or actually had tried marijuana and/or cannabidiol products for a purpose they perceived as medical (often for pain relief and help sleeping) and yet, three years later, there’s been virtually no advancement in the research necessary to provide clinical evidence that rheumatologists and patients need to make decisions about cannabis use for symptom relief in combination with approved treatments” study author W. Benjamin Nowell, PhD, said in a statement.

Nowell is the director of patient-centered research at CreakyJoints and principal investigator of the ArthritisPower Research Registry.

“Without this research, it is impossible to develop clinical guidelines for medicinal cannabis in the U. S., which is vital for patients seeking the full range of treatment options to explore in partnership with their physicians,” Nowell continued. “The best way to treat rheumatic conditions is through the use of U.S. Food and Drug Administration approved medications, which are backed by evidence demonstrating their effectiveness and safety profile.”

As the experts point out in their review, there are currently only three cannabis-related drugs (formulations of cannabidiol, dronabinol, and nabilone) that have been approved by the FDA, and none of these medications are currently approved for treating pain or other symptoms relating to rheumatic disease.

Recommendations for clinicians

The review concludes by discussing several tips for rheumatologists and clinicians when discussing medical cannabis with rheumatic disease patients. The recommendations for clinicians include:

Ensure patients understand that medical cannabis is not an alternative to other guideline-based treatments, which should be continued.

Consider the most common reasons why patients may have interest in medicinal cannabis (pain relief, sleep) and offer alternative treatments where appropriate, but also acknowledge that some individuals may prefer a trial of medical cannabis over other options, including opioids.

Educate patients about the lack of clinical research but recognize that some individuals may still have symptomatic relief with medicinal cannabis.

Ensure understanding of short-term adverse events (including immediate psychomotor effects, dizziness, appetite changes, effect on mood) and warn of the unknown long-term risks of medical cannabis.

Discourage medicinal cannabis use in patients with rheumatic disease who are under age 25.

Such recommendations are important, they say, as due to its contradictory legal status there are currently no official clinical guidelines for medicinal cannabis treatments in the United States.

“Although the clinical evidence about cannabis for rheumatic disease pain is lacking, it is nevertheless important to educate patients about the known benefits and risks of alternative treatments, including medical cannabis,” study author Dr Stuart Silverman, a clinical professor of medicine at University of California, Los Angeles, said in a statement.

“As a rheumatologist who treats patients with pain, I am aware that some of my patients have found cannabis to be an effective option when traditional medications fail to reduce their pain.”

“I am open to discussing medical cannabis when patients express an interest in its use,” Silverman added. “Then, if they choose to use it, I follow them closely to monitor efficacy and any side effects and to ensure that they do not consider it as a replacement for FDA-approved disease-modifying drugs.”