Researchers Suggest Cons of Cannabinoids in Rheumatology Outweigh Pros

When evaluating whether cannabinoids used to treat chronic pain are a “friend” or “foe” of rheumatology, researchers suggested that their adverse events (AEs) and drug interactions outweigh the benefits and make it a “foe.”

Their review, which was focused on the United Kingdom, was published in Musculoskeletal Care.

Cannabinoids are natural compounds found in the cannabis plant and are currently licensed to treat specific medical conditions in the United Kingdom. Although guidelines from the National Institute for Health and Care Excellence advise against using cannabinoids for chronic pain, most UK rheumatologists reported having patients who use them or have considered using them.

The authors said positive patient-reported outcomes and current research still suggest cannabinoids may be a “friend.”

“We were unable to arrive at a definite answer for our question posed, however on the balance of probabilities we can conclude cannabinoids to be a ‘foe’,” the review authors wrote. “Under these circumstances, a disease and drug focussed research is need of the hour to answer the unresolved question.”

In some conditions such as fibromyalgia and osteoarthritis, the authors said cannabinoids can even act as a “bystander” and require further evaluation.

The authors conducted a review of 613 research articles regarding cannabinoids’ mechanism of action, AEs, and drug interactions in rheumatological conditions.

Regarding the mechanism of action, the authors found that inhalation through a vaporizer had a more rapid effect, compared with oral ingestion which had a slower and more sustained effect. Regardless of how the drug is taken, it acts through cannabinoid receptors 1 and 2, which are primary stress response modulators in the brain.

Supporting the idea of them being a “foe,” a systematic review of medical cannabinoids demonstrated that their most consistent effects are their AEs. Some of the most common AEs were dizziness, nausea, dry mouth, tachycardia, and agitation, and cannabinoids were also tied to dependence and addiction.

When reviewing their use specifically to treat pain, spasticity, and vomiting, the authors also found that the drug’s AEs—dizziness, confusion, sedation, and dissociation—led to more patients stopping treatment. Additionally, between 35% and 70% of patients using cannabinoids reported “feeling high” during treatment.

There are also concerns of how cannabinoids may interact with other drugs, and the authors found that in vitro and human data in this area are insufficient.

“However, pending further data, cannabis are presumed to act as substrate of CYP3A4, CYP2C9 and CYP2C19,” they noted. “Therefore, they have potential interactions with many commonly used drugs.”

A few drugs have not shown any predictable interactions with cannabinoids, including adalimumab, methotrexate, hydroxychloroquine, sulfasalazine, mycophenolate mofetil, mesalazine, etanercept, abatacept, infliximab or rituximab. There were also no significant interactions predicted between cannabinoids and either interleukin (IL)‐1 or IL‐6 receptor antagonists.

As noted throughout the review, available data is limited, and the effects of medical cannabinoids in patients with rheumatoid arthritis need to be further researched.

“Inadequate knowledge and insufficient evidence often results in lack of confidence among treating physicians,” the authors wrote. “With available information on significant interaction with CYP450, it is imperative treating physicians should be aware of various aspects of cannabinoid usage in clinical practice.”

Reference

Jain N, Moorthy A. Cannabinoids in rheumatology: friend, foe or a bystander? Musculoskeletal Care. Published online April 27, 2022. doi:10.1002/msc.1636