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Meta-Analysis
. 2017 Aug;42(9):1752-1765.
doi: 10.1038/npp.2017.51. Epub 2017 Mar 22.

Opioid-Sparing Effect of Cannabinoids: A Systematic Review and Meta-Analysis

Suzanne Nielsen  1   2 , Pamela Sabioni  3 , Jose M Trigo  3 , Mark A Ware  4 , Brigid D Betz-Stablein  5 , Bridin Murnion  6   7 , Nicholas Lintzeris  2   6 , Kok Eng Khor  8 , Michael Farrell  1 , Andrew Smith  9 , Bernard Le Foll  3
Affiliations
Meta-Analysis

Opioid-Sparing Effect of Cannabinoids: A Systematic Review and Meta-Analysis

Suzanne Nielsen et al. Neuropsychopharmacology. 2017 Aug.

Abstract

Cannabinoids, when co-administered with opioids, may enable reduced opioid doses without loss of analgesic efficacy (ie, an opioid-sparing effect). The aim of this study was to conduct a systematic review to determine the opioid-sparing potential of cannabinoids. Eligible studies included pre-clinical and clinical studies for which the outcome was either analgesia or opioid dose requirements. Clinical studies included controlled studies and case series. We searched Scopus, Cochrane Database of Systematic Reviews, Medline, and Embase. Nineteen pre-clinical and nine clinical studies met the search criteria. Seventeen of the 19 pre-clinical studies provided evidence of synergistic effects from opioid and cannabinoid co-administration. Our meta-analysis of pre-clinical studies indicated that the median effective dose (ED50) of morphine administered in combination with delta-9-tetrahydrocannabinol (delta-9-THC) is 3.6 times lower (95% confidence interval (CI) 1.95, 6.76; n=6) than the ED50 of morphine alone. In addition, the ED50 for codeine administered in combination with delta-9-THC was 9.5 times lower (95% CI 1.6, 57.5, n=2) than the ED50 of codeine alone. One case series (n=3) provided very-low-quality evidence of a reduction in opioid requirements with cannabinoid co-administration. Larger controlled clinical studies showed some clinical benefits of cannabinoids; however, opioid dose changes were rarely reported and mixed findings were observed for analgesia. In summary, pre-clinical studies provide robust evidence of the opioid-sparing effect of cannabinoids, whereas one of the nine clinical studies identified provided very-low-quality evidence of such an effect. Prospective high-quality-controlled clinical trials are required to determine the opioid-sparing effect of cannabinoids.

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Figures

Figure 1
Figure 1
PRISMA diagram showing study identification. PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses.
Figure 2
Figure 2
Forrest plot for meta-analysis examining the opioid-sparing effect of delta-9-THC when co-administered with morphine. Note: all mean difference and SD values are of log10ED50. THC, tetrahydrocannabinol.
Figure 3
Figure 3
Forrest plot for meta-analysis examining the opioid-sparing effect of delta-9-THC when co-administered with codeine. Note: all mean difference and SD values are of log10ED50. THC, tetrahydrocannabinol.
Figure 4
Figure 4
Funnel plot showing data from the six studies included in the meta-analysis. MD, mean difference, SE, standard error.
See this image and copyright information in PMC

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