Efficacy and safety of cannabinoid treatments in the rheumatic diseases: A systematic review of randomized controlled trials

OBJECTIVES: The endocannabinoid system functions to maintain homeostasis in the human body and thereby has effects on modulation of pain and inflammation. Cannabinoid preparations are available as synthetic or plant derived products and may be effective for the management of musculoskeletal pain. We have conducted a systematic review to examine the evidence for efficacy and side effects of cannabinoids (phyto- and syntheto-) in rheumatology care. METHODS: A literature search was conducted of MEDLINE; Embase Classic + Embase; BIOSIS Previews; Scopus; CENTRAL; DARE; CINAHL; PsycINFO; AMED, with additional searches in ClinicalTrials.gov, International Clinical Trials Registry Platform, Current Controlled Trials, Natural Standard, various Drug and Device Regulatory Approval Sites, Web of Science and Scopus. Included were RCT’s in rheumatology patients with pain and sleep disturbance outcomes. Study quality was assessed using the JADAD scale (out of 5). RESULTS: Of the 1407 articles screened, 12 underwent full text examination. Excluded were survey reports, observational studies, case series, case reports and commentaries, with 7 remaining articles. Of these, 3 were excluded: two included patients with non-rheumatic diseases, 1 was an open-label study of effect of THC on experimentally induced pain. The remaining 4 studies comprised 201 patients (58 RA, 72 FM, and 74 OA). One study examined the effect of nabiximols in RA, two studies examined nabilone in FM (one a non-inferiority study with amitriptyline as comparator), and one examined effect of a fatty acid amide hydrolase-1 (FAAH1) inhibitor in OA. The quality of the trials was good, with a mean 3.75 JADAD score. The study of FAAH1 inhibitor was stopped at interim analysis for futility. For the remaining 3 trials, duration was from 5-8 weeks, with significant analgesic effect in two, significant sleep effect in two, and one in FM reporting improved quality of life. No serious adverse events were reported, with dizziness and drowsiness the most common adverse effects for about a quarter of patients. There were no studies of inhaled herbal cannabis identified. CONCLUSION: Small sample sizes, heterogeneity of rheumatic conditions and products, only a single comparative trial and absence of any study of herbal cannabis allow for only limited conclusions. The results suggest that pain relief and positive effect on sleep may have some potential for therapeutic benefit for rheumatic patients, but in view of this small body of current evidence, cannabinoid treatments cannot be recommended for management of rheumatic complaints.