Only four short-term, randomized trials have addressed the safety, efficacy, and tolerability of cannabinoids for treating rheumatic diseases, and all have methodologic weaknesses and a high risk of bias, according to a qualitative review of data published since 1946.
“There is low-quality evidence suggesting that cannabinoids may be associated with improvements in pain and sleep quality in rheumatoid arthritis and fibromyalgia. Clinical positive effects for the studies assessed in this review must be balanced by the reported adverse events,” wrote Dr. Mary-Ann Fitzcharles of McGill University, Montreal, and her colleagues (Arthritis Care Res. 2015 Nov 9. doi: 10.1002/acr.22727).
The four randomized clinical trials, ranging in duration from 2 to 8 weeks, included one with 58 rheumatoid arthritis patients, two with a total of 71 fibromyalgia patients, and one with 74 osteoarthritis patients. Three trials met their respective primary endpoints and found a statistically significant effect of cannabinoids on pain (in two studies), sleep (in two studies), and improved quality of life (in one study). The investigators noted a high incidence (generally observed in 25%-50% of subjects) of mild to moderate side effects (dizziness, drowsiness, nausea, dry mouth) and many methodologic weaknesses in the evaluated data. The study that tested a fatty acid amide hydrolase inhibitor in osteoarthritis patients was stopped early due to futility. The other three completed studies were associated with an overall high risk of bias.
One of the two fibromyalgia studies was a randomized, double-blind, placebo-controlled trial conducted in 2008 that assessed nabilone in 40 fibromyalgia patients. Nabilone treatment led to significant decreases in the visual analog scale for pain (–2.04, P less than .02) at 4 weeks. A second fibromyalgia trial from 2010 compared amitriptyline to nabilone in 31 subjects and found the latter agent to be superior on the primary endpoint of difference in score on the Insomnia Severity Index (difference = 3.2; 95% confidence interval, 1.2-5.3). A 2006 rheumatoid arthritis trial found that cannabis-based Sativex demonstrated a clinically meaningful advantage over placebo for the primary endpoint of morning pain on movement (difference of –0.95, 95% CI, –1.83 to –0.02; P = .044). No trials assessed herbal cannabis.
“It is not currently possible to recommend this category of treatments as therapy for patients with rheumatic diseases. Any conclusions based on these studies remain tenuous and call for larger, well controlled clinical trials to better understand potential benefits and risks as pertaining to rheumatic conditions,” Dr. Fitzcharles and her coauthors wrote.
No relevant financial disclosures were reported.