In countries that have legalised medical Cannabis, a significant percentage of patients are thought to use the medication in order to ease pain and sleep loss caused by musculoskeletal and rheumatic diseases. For example, a US survey showed that 37% of 1,059 patients of such disorders reported medical Cannabis use.
There are striking rates of Cannabis use among patients with rheumatic conditions such as rheumatoid arthritis; soft tissue rheumatism; osteoarthritis; or fibromyalgia. However, there have been few clinical studies assessing its efficacy. The number of trials considered to be reliable is even smaller.
This point was highlighted in a 2016 review by Fitzcharles et al from the American College of Rheumatology. The reviewers initially identified 1663 studies that were relevant to the area of study. However, following further screening, only four of these studies were assessed in detail.
Pain Relief and Improved Sleep in Rheumatic Conditions
All four of the studies aimed to compare the pain-relieving ability of cannabinoid preparations, in comparison to either placebo or an active comparator. Two of the studies assessed their ability to improve sleep.
The fourth study, which aimed to examine the efficacy of a FAAH inhibitor, was stopped at the interim analysis for futility.
Nabiximols
The first of the studies assessed the use of Nabiximols for the treatment of Rheumatoid Arthritis. Nabiximols is a preparation of cannabinoids extracted from the Cannabis plant. The double-blind, randomised trial monitored 58 patients over a five-week period. Over this time, improvements in pain and sleep quality were observed in the treatment group.
Nabiximols was well-tolerated among the patients, with only one patient withdrawing from the group due to an unrelated surgery. However, adverse effects were more commonly reported among those given the drug, rather than the placebo.
These included dizziness (26%); dry mouth (13%); light-headedness (11%); and nausea and falls (6%). Furthermore, this study only assessed the efficacy of Nabiximols on symptoms of Rheumatoid Arthritis.
No studies were identified by this review that assessed Nabiximols for any other inflammatory rheumatic conditions.
Nabilone
Two of the four trials assessed the efficacy of Nabilone, a synthetic preparation of the cannabinoid THC. A total of 71 Fibromyalgia patients were recruited in the two trials and were given Nabilone. The effects of the active treatment were observed alongside either a placebo, or Amitriptyline (a drug widely used as a pain killer, and an antidepressant at higher doses).
The first study observed 40 fibromyalgia patients given either Nabilone or a placebo over a four-week treatment period. The study showed that Nabilone was associated with a statistical improvement in pain at the fourth week of treatment. This study did not measure differences in sleep quality experienced by participants.
The drug was also shown to be reasonably well-tolerated, with five withdrawing from the treatment group: two gave no reason for their withdrawal; two complained of dizziness/disorientation, nausea, and headache; and one of drowsiness.
The second study observed the effects of Nabilone, in comparison to Amitriptyline, in 31 fibromyalgia patients. This was a crossover trial in which all patients were given both Nabilone and Amitriptyline for a two-week period, with a two-week ‘wash-out’ period. No significant differences were detected between the two treatments for pain relief.
For sleep quality measures, it was observed that Nabilone was noninferior to Amitriptyline. Nabilone did show a marginal advantage to Amitriptyline when sleep quality was measured by the Insomnia Severity Index. However, it did not perform better according to the Leeds Sleep Evaluation Questionnaire.
However, adverse side effects, such as dizziness, drowsiness, nausea, and dry mouth were more commonly reported in the Nabilone treatment group.
Medical Cannabis for the Treatment of Rheumatic Diseases
Although some of these findings demonstrate promising precedent for the consideration of cannabinoids in the treatment of rheumatic conditions, current evidence is lacking and at high risk of bias.
Each of the four studies was identified to be at High Risk of bias when measured against the ‘Risk of Bias’ tool in the Cochrane Handbook for Systematic Reviews of Interventions. All of the studies had significantly low patient numbers – one of the qualifications for ‘High Risk of bias’. This means that the results from the studies, though promising in some cases, could reasonably be considered to be completely random.
In their review of available studies, Fitzcharles et al also highlight this:
“Extremely small sample sizes, short study duration, heterogeneity of rheumatic conditions and products, and absence of studies of herbal cannabis [whole flower/full-plant extract] allow for only limited conclusions for the effects of cannabinoids in rheumatic conditions.”
The medical research of Cannabis is subject to strict supply guidelines, which has limited the number of high-quality studies. The need for randomised controlled trials may also dispel the findings of other forms of research which may more accurately demonstrate the potential benefits and shortcomings of medical Cannabis.
Pharmaceutical Cannabis products (such as Nabilone and Sativex) are currently favoured for clinical trials. This is because it is easier to guarantee a constant quality in these preparations – particularly in the legislative climate that currently exists in much of the world. In contrast, many patients, both official and non-official, use medical Cannabis in herbal, or flower, form.
This is true of both patients in jurisdictions with legalised Cannabis and those without. For example, the Centre for Medicinal Cannabis reported that up to 1.4 million people in the UK use illegal Cannabis to treat diagnosed health conditions.
However, as patients and medical professionals become more open to the potential of medical Cannabis, calls for research are increasing. This data is needed to improve our understanding of the potential of medical Cannabis to treat many conditions, including rheumatic diseases.
