ABSTRACT: Background:For patients with chronic, non-cancer pain, traditional pain-relieving medications include opioids, which have shown benefits but are associated with increased risks of addiction and adverse effects. Medical cannabis has emerged as a treatment alternative for managing these patients and there has been a rise in the number of randomized clinical trials in recent years; therefore, a systematic review of the evidence was warranted. Objective:To analyze the evidence surrounding the benefits and harms of medical cannabinoids in the treatment of chronic, non-cancer-related pain. Design:Systematic review with meta-analysis. Data sources:Medline, Embase, CINAHL, SCOPUS, Google Scholar, and Cochrane Databases. Eligibility criteria:English language randomized clinical trials of cannabinoids for the treatment of chronic, non-cancer-related pain. Data extraction and synthesis:Study quality was assessed using the Cochrane risk of bias tool. All stages were conducted independently by a team of 6 reviewers. Data were pooled through meta-analysis with different durations of treatment (2?weeks, 2?months, 6?months) and stratified by route of administration (smoked, oromucosal, oral), conditions, and type of cannabinoids. Main outcomes and measures:Patient-reported pain and adverse events (AEs). Results:Thirty-six trials (4006 participants) were included, examining smoked cannabis (4 trials), oromucosal cannabis sprays (14 trials), and oral cannabinoids (18 trials). Compared with placebo, cannabinoids showed a significant reduction in pain which was greatest with treatment duration of 2 to 8?weeks (weighted mean difference on a 0-10 pain visual analogue scale -0.68, 95% confidence interval [CI], -0.96 to -0.40, I 2?=?8%, P??.05 in all the 3 durations of treatment); cannabinoids had a smaller reduction in pain due to multiple sclerosis compared with placebo relative to other neuropathic pain (P[interaction]?=?.05) within 2?weeks and the difference was not significant relative to pain due to rheumatic arthritis; nabilone had a greater reduction in pain compared with placebo relative to other types of cannabinoids longer than 2?weeks of treatment but the difference was not significant (P[interaction]?>?.05). Serious AEs were rare, and similar across the cannabinoid (74 out of 2176, 3.4%) and placebo groups (53 out of 1640, 3.2%). There was an increased risk of non-serious AEs with cannabinoids compared with placebo. Conclusions:There was moderate evidence to support cannabinoids in treating chronic, non-cancer pain at 2?weeks. Similar results were observed at later time points, but the confidence in effect is low. There is little evidence that cannabinoids increase the risk of experiencing serious AEs, although non-serious AEs may be common in the short-term period following use.
