Cannabinoids versus placebo or no intervention for pain: protocol for a systematic review with meta-analysis and trial sequential analysis.

INTRODUCTION: Pain is a frequent clinical symptom with significant impact on the patient's well-being. Therefore, adequate pain management is of utmost importance. While cannabinoids have become a more popular alternative to traditional types of pain medication among patients, the quality of evidence supporting the use of cannabinoids has been questioned. The beneficial and harmful effects of cannabinoids in patients with pain is unknown. Accordingly, we aim to assess the efficacy, tolerability and safety of cannabinoids (herbal, plant-derived extracts and synthetic) compared with placebo or no intervention for any type of pain. METHODS AND ANALYSES: We will conduct a systematic review of randomised clinical trials with meta-analysis and Trial Sequential Analysis to assess the beneficial and harmful effects of cannabinoids in any dose, formulation and duration. We will accept placebo or no treatment as control interventions. We will include participants with any type of pain (acute and chronic pain, cancer-related pain, headache, neuropathic pain or any other types of pain). We will systematically search The Cochrane Library, MEDLINE, Embase, Science Citation Index and BIOSIS for relevant literature. We will follow the recommendations by Cochrane and the Preferred Reporting Items for Systematic Review and Meta-Analysis statement. The risk of systematic errors (bias) and random errors (play of chance) will be assessed. The overall certainty of evidence will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation approach. ETHICS AND DISSEMINATION: Ethical approval is not a requirement since no primary data will be collected. The findings of this systematic review will be submitted for peer-reviewed publication and disseminated in national and international conferences. DISCUSSION: Although cannabinoids are now being used to manage different pain conditions, the evidence for the clinical effects are unclear. The present review will systematically assess the current evidence for the benefits and harms of cannabinoids to inform practice and future research.