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Meta-Analysis
, 64 (2), e78-e94

Systematic Review of Systematic Reviews for Medical Cannabinoids: Pain, Nausea and Vomiting, Spasticity, and Harms

Affiliations
Meta-Analysis

Systematic Review of Systematic Reviews for Medical Cannabinoids: Pain, Nausea and Vomiting, Spasticity, and Harms

G Michael Allan et al. Can Fam Physician.

Abstract

Objective: To determine the effects of medical cannabinoids on pain, spasticity, and nausea and vomiting, and to identify adverse events.

Data sources: MEDLINE, the Cochrane Database, and the references of included studies were searched.

Study selection: Systematic reviews with 2 or more randomized controlled trials (RCTs) that focused on medical cannabinoids for pain, spasticity, or nausea and vomiting were included. For adverse events, any meta-analysis for the conditions listed or of adverse events of cannabinoids was included.

Synthesis: From 1085 articles, 31 relevant systematic reviews were identified including 23 for pain, 5 for spasticity, 6 for nausea and vomiting, and 12 for adverse events. Meta-analysis of 15 RCTs found more patients taking cannabinoids attained at least a 30% pain reduction: risk ratio (RR) of 1.37 (95% CI 1.14 to 1.64), number needed to treat (NNT) of 11. Sensitivity analysis found study size and duration affected findings (subgroup differences, P ≤ .03), with larger and longer RCTs finding no benefit. Meta-analysis of 4 RCTs found a positive global impression of change in spasticity (RR = 1.45, 95% CI 1.08 to 1.95, NNT = 7). Other results were not consistently statistically significant, but when positive, a 30% or more improvement in spasticity had an NNT of 10. Meta-analysis of 7 RCTs for control of nausea and vomiting after chemotherapy found an RR of 3.60 (95% CI 2.55 to 5.09) with an NNT of 3. Adverse effects caused more patients to stop treatment (number needed to harm [NNH] of 8 to 22). Individual adverse events were very common, including dizziness (NNH = 5), sedation (NNH = 5), confusion (NNH = 15), and dissociation (NNH = 20). "Feeling high" was reported in 35% to 70% of users. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) evaluation reduced evidence ratings of benefit to low or very low.

Conclusion: There is reasonable evidence that cannabinoids improve nausea and vomiting after chemotherapy. They might improve spasticity (primarily in multiple sclerosis). There is some uncertainty about whether cannabinoids improve pain, but if they do, it is neuropathic pain and the benefit is likely small. Adverse effects are very common, meaning benefits would need to be considerable to warrant trials of therapy.

Figures

Figure 1.
Figure 1.
Responder meta-analysis of patients attaining ≥30% reduction in pain with medical cannabinoids compared with placebo *Mantel-Haenszel method, random-effects meta-analysis. Meta-analysis of studies from Whiting et al (GW Pharmaceuticals, 2005, Johnson, 2010, Portenoy, 2012), Andreae et al (Abrams, 2007, Ellis, 2009, Ware, 2010, Wilsey, 2008, Wilsey, 2013), and Petzke et al (Berman, 2004, Langford, 2013, Lynch, 2014, Nurmikko, 2007, Rog, 2005, Selvarajah, 2010, Serpell, 2014).
Figure 2.
Figure 2.
Responder meta-analysis of patients having control of their nausea and vomiting resulting from chemotherapy: A) Medical cannabinoid compared with placebo; B) medical cannabinoid compared with another antiemetic (neuroleptics). *Mantel-Haenszel method, fixed-effects meta-analysis. Mantel-Haenszel method, random-effects meta-analysis. Meta-analysis of studies for Figure 2A from Whiting et al (Meiri, 2007, Duran, 2010, Melham-Bertrandt, 2014), Smith et al (Sallan, 1975, Wada, 1982), and Machado Rocha et al (Frytak, 1979, Orr, 1980). Meta-analysis of studies for Figure 2B from Smith et al (Frytak, 1979, Herman, 1979, Lane, 1991, McCabe, 1988) and Machado Rocha et al (Ahmedzai, 1983, Chan, 1987, Dalzell, 1986, Hutcheon, 1983, Johansson, 1982, Niederle, 1986, Niiranen, 1985, Orr, 1980, Sallan, 1980, Sheidler, 1984).
Figure 3.
Figure 3.
Responder meta-analysis of patients with a positive global impression of change for spasticity with medical cannabinoids compared with placebo *Mantel-Haenszel method, random-effects meta-analysis. Meta-analysis of studies from Whiting et al (Berman, 2007, Collin, 2007, Wade, 2004) and Wade et al (Collin, 2010).

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