Adding cannabinoids to opioids does not appear to improve control of cancer-related pain in adults with late-stage disease, authors of a systematic review and meta-analysis contend.
Among 1,442 participants in five randomized controlled trials of cannabinoids compared with placebo, there was no significant difference in the primary outcome of pain intensity scores, reported Elaine G. Boland, MD, PhD, of Hull University Teaching Hospitals NHS Trust in Cottingham, England, and colleagues.
“For a medication to be useful, there needs to be a net overall benefit, with the positive effects (analgesia) outweighing adverse effects. None of the included phase III studies show benefit of cannabinoids,” they wrote. Their report is in BMJ Supportive & Palliative Care.
According to NORML, the National Organization for the Reform of Marijuana Laws, 33 U.S. states currently have legalized medical use of marijuana or cannabinoids, and Dr. Boland and coauthors report that medical marijuana is legal in some 40 nations worldwide.
Survey data and a randomized sample of urine tests from a cancer center in Washington State, were marijuana is legal, show that cannabis or cannabinoid use is common among cancer patients. Despite its widespread use, good quality evidence of the efficacy of cannabis for control of cancer pain is sparse, the investigators said.-
They designed a systematic review and meta-analysis to identify randomized controlled trials with a low risk for bias, eventually settling on five with a total of 1,442 patients. Four of the studies evaluated nabiximols (Sativex), an oromucosal formulation of delta-9-tetrahydrocannabinol:cannabidiol (THC:CBD), and one tested THC:CBD or THC abstract vs. placebo.
To bolster confidence in their results, the investigators contacted the authors of the included studies to obtain additional findings and information about each study’s design.
They found that in the pooled data there was no significant difference between cannabinoids and placebo for the difference in average pain on a Numeric Rating Scale (NRS). The mean difference was –0.21 (P = .14) and did not reach significance when the analysis was restricted to phase 3 trials (mean difference –.02, P = .80).
For the secondary outcomes of adverse events and dropouts, they found that cannabinoids were associated with significantly higher risk for somnolence (odds ratio [OR] 2.69, P less than .001) and dizziness (OR 1.58, P = .05), and that dropouts due to adverse events were more frequent in the cannabinoid arms.
The investigators acknowledged that the study was limited by its reliance on the NRS pain score “as this simple instrument does not capture the complexity of pain especially when it has been [a] long-standing problem,” and by the possibility that vagaries in the use of the oromucosal spray might affect the absorption and efficacy of the cannabinoids.
The authors did not report a funding source. No conflicts of interest were reported.
SOURCE: Boland EG et al. BMJ Supportive & Palliative Care 2020 Jan 20. doi: 10.1136/bmjspcare-2019-002032.