patrick.net

Amid growing cannabis access, data for rheumatology benefit still 'fraught with bias'

There is no doubt that patients with rheumatic and autoimmune diseases are taking full advantage of relaxed laws in the United States surrounding recreational cannabis use.

The question, however, is whether or not the improvements in pain, inflammation or sleep they are experiencing are attributable to true medicinal effects.

In their recent study in Arthritis Care & Research, Wipfler and colleagues conducted a trial of 11,006 patients with various arthritic conditions in the U.S. Results showed an increase in cannabis use from 6.3% in 2014 to 18.4% in 2019. The steepest increases were seen in states where recreational marijuana use is legalized.

Similarly, Mary-Ann Fitzcharles, MD, senior physician in the division of rheumatology at the Louise and Alan Edwards Pain Management Center at McGill University Health Center, Montreal, and colleagues, conducted an online survey of 1,047 rheumatology patients in Canada after recreational legalization of marijuana. Results published in ACR Open Rheumatology showed that cannabis use tripled in this group after legalization.

Despite this uptick, Fitzcharles explained why there are still far more questions than answers surrounding cannabis use in the rheumatology space. “The preclinical models of pain and inflammation, even joint inflammation, have shown excellent effect of cannabinoids,” she said. “But a preclinical study does not directly translate into the clinical setting.”

While a true analgesic effect is indeed possible with cannabis use, Fitzcharles suggested that an “expectation of a positive effect” could also be influencing how patients feel. “There may also be a true placebo effect for some patients,” she added.

But the issue, in fact, is actually much more complicated than that, according to Donald Abrams, MD, professor in the department of medicine and integrative oncologist at the University of California, San Francisco. “It is an impossible effort to try to study anything about cannabis because of the laws in this country,” he said.

But prohibitive regulations are just one factor, according to Abrams, who talked at length about the various forms of tetrahydrocannabinol (THC) and cannabidiol (CBD) available both legally and illegally in the U.S.

“There is CBD, THC, Delta-9 THC, Delta-8 THC; there are various concentrations of THC and CBD in different products; patients may take it orally and there are creams and vapors,” Abrams said. “There is too much variety in the products available, which makes any attempt to understand their impact fraught with bias.”

That said, Abrams noted that some form of cannabis has been used therapeutically for “thousands of years.” He believes that this potentially “useful botanical” is almost certainly safer than tobacco and alcohol and should be studied rigorously to answer the questions of whether it has benefit, and what those benefits are. “Stop demonizing it,” he said.

The first step in this process may be to further understand why cannabis products may or may not have a positive impact on rheumatology patients in the first place.

Understanding the Mechanism
For Ronald J. Rapoport, MD, FACR, chief of the division of rheumatology at Southcoast Health in Massachusetts, the fact that there is an endocannabinoid system in the human body is the obvious place to start. “The cannabinoids that are made in our body’s endocannabinoid system are involved in the normal functioning of such things as the nervous system,” he said, noting that the endocannabinoid system may be involved in everything from Alzheimer’s disease to multiple sclerosis.

“There are two confirmed receptor subtypes for cannabis in humans,” Rapoport continued. “The cannabinoid (CB)-1 receptor agonists may act on nociceptors in the dorsal horn of the spinal cord and may reduce pain because of this. The CB-2 receptor may have a positive effect on reducing inflammation and autoimmunity.”

CB-2 is not as ubiquitous as CB-1, according to Rapoport. However, there is some evidence that CB-2 binds to immune cells. “The CB-2 receptor has a high density on immune modulating cells and may influence such things as immune cell migration and cytokine release,” he said.

There is another component of the cannabinoid system that may be of particular interest to rheumatologists. “CB-2 also seems to be involved in maintaining skeletal integrity as it is noted to be found in osteocytes, osteoclasts and osteoblasts,” Rapoport said.

Rapoport also described the mechanism by which the endocannabinoid system may impact pain. “We have to emphasize that the CB-2 selective agonist may be helpful not only in reducing inflammation but also potentially in reducing established hypersensitivity in such things as skin disorders and peripheral pain,” he said.

https://www.healio.com/news/rheumatology/20210824/amid-growing-cannabis-access-data-for-rheumatology-benefit-still-fraught-with-bias