TY - JOUR
T1 - Cannabinoids versus placebo for pain
T2 - A systematic review with meta-analysis and Trial Sequential Analysis
AU - Barakji, Jehad
AU - Korang, Steven Kwasi
AU - Feinberg, Joshua
AU - Maagaard, Mathias
AU - Mathiesen, Ole
AU - Gluud, Christian
AU - Jakobsen, Janus Christian
N1 - Copyright: © 2023 Barakji et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2023
Y1 - 2023
N2 - OBJECTIVES: To assess the benefits and harms of cannabinoids in participants with pain.DESIGN: Systematic review of randomised clinical trials with meta-analysis, Trial Sequential Analysis, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.DATA SOURCES: The Cochrane Library, MEDLINE, Embase, Science Citation Index, and BIOSIS.ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Published and unpublished randomised clinical trials comparing cannabinoids versus placebo in participants with any type of pain.MAIN OUTCOME MEASURES: All-cause mortality, pain, adverse events, quality of life, cannabinoid dependence, psychosis, and quality of sleep.RESULTS: We included 65 randomised placebo-controlled clinical trials enrolling 7017 participants. Fifty-nine of the trials and all outcome results were at high risk of bias. Meta-analysis and Trial Sequential Analysis showed no evidence of a difference between cannabinoids versus placebo on all-cause mortality (RR 1.20; 98% CI 0.85 to 1.67; P = 0.22). Meta-analyses and Trial Sequential Analysis showed that cannabinoids neither reduced acute pain (mean difference numerical rating scale (NRS) 0.52; 98% CI -0.40 to 1.43; P = 0.19) or cancer pain (mean difference NRS -0.13; 98% CI -0.33 to 0.06; P = 0.1) nor improved quality of life (mean difference -1.38; 98% CI -11.81 to 9.04; P = 0.33). Meta-analyses and Trial Sequential Analysis showed that cannabinoids reduced chronic pain (mean difference NRS -0.43; 98% CI -0.72 to -0.15; P = 0.0004) and improved quality of sleep (mean difference -0.42; 95% CI -0.65 to -0.20; P = 0.0003). However, both effect sizes were below our predefined minimal important differences. Meta-analysis and Trial Sequential Analysis indicated that cannabinoids increased the risk of non-serious adverse events (RR 1.20; 95% CI 1.15 to 1.25; P < 0.001) but not serious adverse events (RR 1.18; 98% CI 0.95 to 1.45; P = 0.07). None of the included trials reported on cannabinoid dependence or psychosis.CONCLUSIONS: Cannabinoids reduced chronic pain and improved quality of sleep, but the effect sizes are of questionable importance. Cannabinoids had no effects on acute pain or cancer pain and increased the risks of non-serious adverse events. The harmful effects of cannabinoids for pain seem to outweigh the potential benefits.
AB - OBJECTIVES: To assess the benefits and harms of cannabinoids in participants with pain.DESIGN: Systematic review of randomised clinical trials with meta-analysis, Trial Sequential Analysis, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.DATA SOURCES: The Cochrane Library, MEDLINE, Embase, Science Citation Index, and BIOSIS.ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Published and unpublished randomised clinical trials comparing cannabinoids versus placebo in participants with any type of pain.MAIN OUTCOME MEASURES: All-cause mortality, pain, adverse events, quality of life, cannabinoid dependence, psychosis, and quality of sleep.RESULTS: We included 65 randomised placebo-controlled clinical trials enrolling 7017 participants. Fifty-nine of the trials and all outcome results were at high risk of bias. Meta-analysis and Trial Sequential Analysis showed no evidence of a difference between cannabinoids versus placebo on all-cause mortality (RR 1.20; 98% CI 0.85 to 1.67; P = 0.22). Meta-analyses and Trial Sequential Analysis showed that cannabinoids neither reduced acute pain (mean difference numerical rating scale (NRS) 0.52; 98% CI -0.40 to 1.43; P = 0.19) or cancer pain (mean difference NRS -0.13; 98% CI -0.33 to 0.06; P = 0.1) nor improved quality of life (mean difference -1.38; 98% CI -11.81 to 9.04; P = 0.33). Meta-analyses and Trial Sequential Analysis showed that cannabinoids reduced chronic pain (mean difference NRS -0.43; 98% CI -0.72 to -0.15; P = 0.0004) and improved quality of sleep (mean difference -0.42; 95% CI -0.65 to -0.20; P = 0.0003). However, both effect sizes were below our predefined minimal important differences. Meta-analysis and Trial Sequential Analysis indicated that cannabinoids increased the risk of non-serious adverse events (RR 1.20; 95% CI 1.15 to 1.25; P < 0.001) but not serious adverse events (RR 1.18; 98% CI 0.95 to 1.45; P = 0.07). None of the included trials reported on cannabinoid dependence or psychosis.CONCLUSIONS: Cannabinoids reduced chronic pain and improved quality of sleep, but the effect sizes are of questionable importance. Cannabinoids had no effects on acute pain or cancer pain and increased the risks of non-serious adverse events. The harmful effects of cannabinoids for pain seem to outweigh the potential benefits.
KW - Humans
KW - Chronic Pain/drug therapy
KW - Acute Pain
KW - Cancer Pain
KW - Quality of Life
KW - Cause of Death
UR - http://www.scopus.com/inward/record.url?scp=85147152548&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0267420
DO - 10.1371/journal.pone.0267420
M3 - Review
C2 - 36716312
SN - 1932-6203
VL - 18
JO - PLoS One
JF - PLoS One
IS - 1
M1 - e0267420
ER -