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With the chronic pain and other health issues that many rheumatology patients face every day, it’s natural for rheumatologists and their patients to wonder if cannabinoid treatments are of any help. At this point, there is insufficient evidence to recommend cannabinoid treatments to manage rheumatic diseases, according to a review article published in the May issue of Arthritis Care & Research.1
Lead author Mary-Ann Fitzcharles, MBChB, a rheumatologist at McGill University Health Centre, Montreal, Quebec, and colleagues used Medline, Embase and CENTRAL database searches to pinpoint studies that focused on cannabinoid use for pain, sleep, quality of life, tolerability and safety. Although they found 22 potential articles, the final number of studies was narrowed down to only four; the other articles were excluded because they were reviews, they were not randomized controlled trials or they studied other pain conditions.
The Studies
The four studies included a total of 203 patients—58 with rheumatoid arthritis (RA), 71 with fibromyalgia and 74 with osteoarthritis (OA). One study, from Blake et al in 2006, included 58 patients with RA who received nabiximols or placebo for five weeks.2 Nabiximols are phytocannabinoids extracted from cannabis. The study’s main outcome measures were morning pain on movement and at rest, stiffness and sleep quality. Those in the study had improvement in those areas, as well as in their responses to the short form McGill Pain Questionnaire and Disease Activity Score at 28 joints. The only serious adverse events occurred in two patients in the placebo group; otherwise, side effects included dizziness, dry mouth, lightheadedness, nausea and falls.
A second study focused on the use of nabilone 0.5 to 1 mg twice a day or placebo for four weeks of active treatment (followed by four weeks of observation) in 40 patients with fibromyalgia.3 Investigators measured pain improvement as the primary outcome and tender points and Fibromyalgia Impact Questionnaire (FIQ) responses as secondary outcomes. Although there were improved pain and improved responses to the FIQ anxiety and total score, seven patients withdrew from the study, five of whom were in the treatment group. Two patients withdrew for unreported reasons, two for dizziness and disorientation, and one for drowsiness and headache. Common side effects in the study included drowsiness (reported by almost 50% in the active treatment group), dry mouth, vertigo, ataxia and other effects.
A third study also involved fibromyalgia patients (n=31) and nabilone, but this study compared nabilone with amitriptyline over a six-week period.4 Patients received each drug for two weeks, followed by a two-week washout period. The primary outcome was sleep quality. Patients reported improvement with the Insomnia Severity Index but not with other sleep questionnaire measurements. Dizziness, nausea, drowsiness and dry mouth were commonly reported in the nabilone group. There are no studies yet of nabilone in patients with inflammatory rheumatic conditions, OA or soft-tissue rheumatism, Dr. Fitzcharles and fellow authors wrote.
The final study reviewed included 74 patients with knee OA who received a fatty acid amide hydrolase-1 (FAAH-1) inhibitor called PF-04457845, which was compared with naproxen.5 However, the study stopped because of futility. “While naproxen showed reduction in pain compared to placebo, the FAAH-1 inhibitor did not demonstrate difference from placebo, although the agent was well tolerated, with a safety profile similar to placebo,” the authors wrote.
The use of an FAAH-1 inhibitor has not yet been studied in inflammatory rheumatic conditions or fibromyalgia, the authors reported. They also did not find any studies of dronabinol or herbal cannabis in patients with rheumatic disease.
Significance
With the results of the four studies so varied, the review authors had a hard time making any solid conclusions. “This systematic review has revealed a dearth of studies examining the effects of cannabinoids in a small number of patients with rheumatic disease,” the authors wrote. “No comment can be made regarding effects for herbal cannabis preparations in patients with rheumatic diseases.”
Although the studies did find some statistical improvements in pain and sleep, the side effects of altered perception, dizziness, drowsiness and some gastrointestinal issues are still troublesome, the authors wrote. In fact, for the three completed studies, 25–50% of patients experienced side effects, such as dizziness, drowsiness and cognitive effects; many also reported dry mouth, nausea and constipation. However, there were no serious adverse events in the active treatment groups.
It’s also particularly surprising that with the prevalent use of medical herbal marijuana in the U.S. and Canada, not a single study has been conducted on the effects of marijuana in those with musculoskeletal complaints, Dr. Fitzcharles said.
The Implications
Despite the lack of conclusive evidence from the review, rheumatologists must still be prepared to give patients some guidance on the use of marijuana for their condition. “Rheumatologists will be caring for patients who will be using marijuana, often by self-medication, with or without the knowledge of the treatment physician,” Dr. Fitzcharles said. “This is a current reality and will likely be an increasing practice in the future.”
Rheumatologists need to be educated about the effectiveness of cannabinoids to properly advise patients, she said. “It will be important to maintain a level-headed approach, bolstered by critical appraisal of the literature, and not be swept away by public opinion and advocacy. In the absence of evidence in the rheumatology patient population, we must take note of the current knowledge of both the immediate and long-term risks of marijuana use, mostly derived from studies of recreational users,” she added.
Dr. Fitzcharles perceives a similar interest in medical marijuana by patients and physicians both in her home country of Canada—where medicinal marijuana has been legal since 2001—as well as in the U.S., where its use is increasing each year. One issue that she sees cannabinoid treatments trying to address is pain—always a concern of patients. “Although pain is the most common reason why patients seek care from a rheumatologist, specific pain management has not been featured prominently in rheumatology care in the past. We have been so focused on achieving the best outcome for patients with inflammatory disease that attention to the suffering of patients has often taken second place,” she said. With the concern in North America now on overuse of opioids, Dr. Fitzcharles speculated that there may be a flip to a greater use of cannabis for patients with rheumatic pain—yet another reason why rheumatologists need to be up to speed about its realistic effectiveness.
Further Research Areas
Researchers have work to do in several areas related to rheumatology and cannabinoid treatment, Dr. Fitzcharles said. That includes studies focused on the effects of the whole cannabis plant, which has hundreds of molecules and may interact in unknown ways or on individual molecules; which specific molecules have a therapeutic effect; symptoms that can be best addressed with the use of cannabinoids (e.g., pain or sleep disturbance); how cannabinoids interact with other medications used to treat rheumatic diseases; and short- and long-term adverse effects in patients with rheumatic disease.
“We have no idea at this time about the ideal molecule, dosage, pharmacokinetics, efficacy, or safety of various cannabinoid preparations in the management of rheumatic complaints. Unfortunately, medicinal herbal cannabis use is currently driven by political/financial agendas, and advocacy has outrun science. The health community must maintain a strong voice to demand competent study, and we must maintain a strong voice to demand competent study and protect both patients and society,” Dr. Fitzcharles said.
Dr. Fitzcharles and fellow researchers are working on a study about ingested marijuana in the form of an extracted oil for painful conditions, such as fibromyalgia.
Vanessa Caceres is a medical writer in Bradenton, Fla.
References
- Fitzcharles MA, Ste-Marie PA, Hauser W, et al. Efficacy, tolerability, and safety of cannabinoid treatments in the rheumatic diseases: A systematic review of randomized controlled trials. Arthritis Care Res (Hoboken). 2016 May;68(5):681–688.
- Blake DR, Robson P, Ho M, et al. Preliminary assessment of the efficacy, tolerability, and safety of a cannabis-based medicine (Sativex) in the treatment of pain caused by rheumatoid arthritis. Rheumatology (Oxford). 2006 Jan;45(1):50–52.
- Skrabek RQ, Galimova L, Ethans K, Perry D. Nabilone for the treatment of pain in fibromyalgia. J Pain. 2008 Feb;9(2):164–173.
- Ware MA, Fitzcharles MA, Joseph L, Sheir Y. The effects of nabilone on sleep in fibromyalgia: Results of a randomized controlled trial. Anesth Analg. 2010 Feb 1;110:604–610.
- Huggins JP, Smart TS, Langman S, et al. An efficient randomized, placebo-controlled clinical trial with the irreversible fatty acid amide hydrolase-1 inhibitor PF-04457845, which modulates endocannabinoids but fails to induce effective analgesia in patients with pain due to osteoarthritis of the knee. Pain. 2012 Sep;153(9):1837–1846.
