Cannabis and Cannabinoids for the Treatment of People With Chronic Noncancer Pain Conditions

A Systematic Review and Meta-analysis of Controlled and Observational Studies

Emily Stockings; Gabrielle Campbell; Wayne D. Hall; Suzanne Nielsen; Dino Zagic; Rakin Rahman; Bridin Murnion; Michael Farrell; Megan Weier; Louisa Degenhardt

Disclosures

Pain. 2018;159(10):1932-1954. 

In This Article

Abstract and Introduction

Abstract

This review examines evidence for the effectiveness of cannabinoids in chronic noncancer pain (CNCP) and addresses gaps in the literature by: considering differences in outcomes based on cannabinoid type and specific CNCP condition; including all study designs; and following IMMPACT guidelines. MEDLINE, Embase, PsycINFO, CENTRAL, and clinicaltrials.gov were searched in July 2017. Analyses were conducted using Revman 5.3 and Stata 15.0. A total of 91 publications containing 104 studies were eligible (n = 9958 participants), including 47 randomised controlled trials (RCTs) and 57 observational studies. Forty-eight studies examined neuropathic pain, 7 studies examined fibromyalgia, 1 rheumatoid arthritis, and 48 other CNCP (13 multiple sclerosis–related pain, 6 visceral pain, and 29 samples with mixed or undefined CNCP). Across RCTs, pooled event rates (PERs) for 30% reduction in pain were 29.0% (cannabinoids) vs 25.9% (placebo); significant effect for cannabinoids was found; number needed to treat to benefit was 24 (95% confidence interval [CI] 15–61); for 50% reduction in pain, PERs were 18.2% vs 14.4%; no significant difference was observed. Pooled change in pain intensity (standardised mean difference: −0.14, 95% CI −0.20 to −0.08) was equivalent to a 3 mm reduction on a 100 mm visual analogue scale greater than placebo groups. In RCTs, PERs for all-cause adverse events were 81.2% vs 66.2%; number needed to treat to harm: 6 (95% CI 5–8). There were no significant impacts on physical or emotional functioning, and low-quality evidence of improved sleep and patient global impression of change. Evidence for effectiveness of cannabinoids in CNCP is limited. Effects suggest that number needed to treat to benefit is high, and number needed to treat to harm is low, with limited impact on other domains. It seems unlikely that cannabinoids are highly effective medicines for CNCP.

Introduction

There has been increasing attention to the use of cannabis and cannabinoids in the treatment of chronic noncancer pain (CNCP). Changes in legislation and use globally mean that it is likely that there will be an increase in the coming years in the availability and use of cannabis and cannabinoid products for CNCP. In the United States, these products are most commonly cited for use in CNCP.[48] Chronic noncancer pain conditions are prevalent and rank among the most significant causes of disability globally.[30]

Recent reviews of cannabis and cannabinoids for medicinal purposes have increased our knowledge in the understanding of their effectiveness on pain,[55,88,93] although they are limited in the case of CNCP management and conclusions have been conflicting, with some reviews reporting moderate to large effects,[48,93] whereas others have reported minimal[60] or no benefit.[3] Existing reviews have been limited in their searching for CNCP studies (eg, with a focus on specific types of cannabinoids[2] or study designs[60]), and no single review has considered the following: all types of evidence; different CNCP conditions individually; potential differential effects of different cannabinoids; and the safety of cannabis for patients with CNCP. Each of these limitations reduces our understanding of the evidence for the use of cannabinoids for CNCP.

Chronic noncancer pain conditions are varied, and many people with CNCP live with complex physical and mental health comorbidities.[9,70] Pain is considered by leading clinicians and researchers to be only one of a range of core outcomes that must be considered evaluating interventions for CNCP.[82] The current review addresses the limitations of previous reviews and is the first to examine the evidence for the effectiveness of cannabinoids for CNCP for all study designs, all CNCP types, all types of cannabis and cannabinoids, and using the outcomes specified in the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT).[82]

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