Efficacy, tolerability and safety of cannabis-based medicines for cancer pain A systematic review with meta-analysis of randomised controlled trials

Background. The importance of medical cannabis and cannabis-basedmedicines for cancer pain management needs to be determined. Methods. A systematic literature search until December 2018 included CENTRAL, PubMed, SCOPUS and trial registers. Randomised controlled trials (RCTs) investigating medical cannabis and/or pharmaceutical cannabinoids for pain control in cancer patients with a study duration of at least 2 weeks and a sample size of at least 20 participants per study arm were included. Clinical outcomes comprised efficacy (pain intensity, patient impression of improvement, combined responder, sleep problems, psychological distress, opioid maintenance and breakthrough dosage), tolerability (dropout rate due to adverse events) and safety (nervous system, psychiatric and gastrointestinal side effects; serious adverse events). The quality of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE). Results. Five RCTs with oromucosal nabiximols or tetrahydrocannabinol (THC) including 1534 participants with moderate and severe pain despite opioid therapy were identified. Double blind period of the RCTs ranged between 2 and 5 weeks. Four studies with a parallel design and 1333 patients were available for meta-analysis. The quality of evidence was very low for all comparisons. Oromucosal nabiximols and THC did not differ from placebo in reducing pain, sleep problems, opioid dosages and in the frequency of combined responder, serious adverse events and psychiatric disorders side effects. The number of patients who reported to be much or very much improved was higher with oromucosal nabiximols and THC than with placebo (number needed to treat for an additional benefit 16; 95% confidence interval [CI] 8 to infinite). The dropout rates due to adverse events (number needed to treat for an additional harm [NNTH]: 20; 95% CI 11-100), the frequency of nervous system(NNTH: 10; 95% CI 7-25) and of gastrointestinal side effects (NNTH: 11; 95% CI 7-33) was higher with oromucosal nabiximols and THC than with placebo. Conclusions. Very low quality evidence suggests that oromucosal nabiximols and THC have no effect on pain, sleep problems and opioid consumption in patients with cancer pain with insufficient pain relief from opioids. The completemanuscript is written in English.