Opioid-sparing effect of cannabinoids for analgesia: an updated systematic review and meta-analysis of preclinical and clinical studies

Suzanne Nielsen; Louisa Picco; Bridin Murnion; Bryony Winters; Justin Matheson; Myfanwy Graham; Gabrielle Campbell; Laila Parvaresh; Kok-Eng Khor; Brigid Betz-Stablein; Michael Farrell; Nicholas Lintzeris; Bernard Le Foll

doi:10.1038/s41386-022-01322-4

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Opioid-sparing effect of cannabinoids for analgesia: an updated systematic review and meta-analysis of preclinical and clinical studies

Journal article

Open access

Peer reviewed

Opioid-sparing effect of cannabinoids for analgesia: an updated systematic review and meta-analysis of preclinical and clinical studies

Suzanne Nielsen, Louisa Picco, Bridin Murnion, Bryony Winters, Justin Matheson, Myfanwy Graham, Gabrielle Campbell, Laila Parvaresh, Kok-Eng Khor, Brigid Betz-Stablein, …

Neuropsychopharmacology, Vol.47(7), pp.1315-1330

2022

DOI: https://doi.org/10.1038/s41386-022-01322-4

PMCID: PMC9117273

PMID: 35459926

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Abstract

preclinical research

translational research

Cannabinoid co-administration may enable reduced opioid doses for analgesia. This updated systematic review on the opioid-sparing effects of cannabinoids considered preclinical and clinical studies where the outcome was analgesia or opioid dose requirements. We searched Scopus, Cochrane Central Registry of Controlled Trials, Medline, and Embase (2016 onwards). Ninety-two studies met the search criteria including 15 ongoing trials. Meta-analysis of seven preclinical studies found the median effective dose (ED50) of morphine administered with delta-9-tetrahydrocannabinol was 3.5 times lower (95% CI 2.04, 6.03) than the ED50 of morphine alone. Six preclinical studies found no evidence of increased opioid abuse liability with cannabinoid administration. Of five healthy-volunteer experimental pain studies, two found increased pain, two found decreased pain and one found reduced pain bothersomeness with cannabinoid administration; three demonstrated that cannabinoid co-administration may increase opioid abuse liability. Three randomized controlled trials (RCTs) found no evidence of opioid-sparing effects of cannabinoids in acute pain. Meta-analysis of four RCTs in patients with cancer pain found no effect of cannabinoid administration on opioid dose (mean difference −3.8 mg, 95% CI −10.97, 3.37) or percentage change in pain scores (mean difference 1.84, 95% CI −2.05, 5.72); five studies found more adverse events with cannabinoids compared with placebo (risk ratio 1.13, 95% CI 1.03, 1.24). Of five controlled chronic non-cancer pain trials; one low-quality study with no control arm, and one single-dose study reported reduced pain scores with cannabinoids. Three RCTs found no treatment effect of dronabinol. Meta-analyses of observational studies found 39% reported opioid cessation (95% CI 0.15, 0.64, I2 95.5%, eight studies), and 85% reported reduction (95% CI 0.64, 0.99, I2 92.8%, seven studies). In summary, preclinical and observational studies demonstrate the potential opioid-sparing effects of cannabinoids in the context of analgesia, in contrast to higher-quality RCTs that did not provide evidence of opioid-sparing effects.

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Title: Opioid-sparing effect of cannabinoids for analgesia: an updated systematic review and meta-analysis of preclinical and clinical studies
Authors: Suzanne Nielsen (Corresponding Author) - St Vincent's Hospital Sydney
Louisa Picco (Author) - Monash University
Bridin Murnion (Author) - The University of Sydney
Bryony Winters (Author) - The University of Sydney
Justin Matheson (Author) - Centre for Addiction and Mental Health
Myfanwy Graham (Author) - University of Newcastle Australia
Gabrielle Campbell (Author) - University of the Sunshine Coast, Queensland, School of Health and Behavioural Sciences - Legacy
Laila Parvaresh (Author) - The University of Sydney
Kok-Eng Khor (Author) - UNSW Australia
Brigid Betz-Stablein (Author) - The University of Queensland
Michael Farrell (Author) - UNSW Australia
Nicholas Lintzeris (Author) - The University of Sydney
Bernard Le Foll (Author) - University of Toronto
Publication details: Neuropsychopharmacology, Vol.47(7), pp.1315-1330; 16
Publisher: Nature Publishing Group
Date published: 2022
DOI: 10.1038/s41386-022-01322-4
ISSN: 1740-634X
PMID: 35459926; PMC9117273
Copyright note: Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Grant note: 1163961 / NHMRC Research Fellowship; National Health and Medical Research Council (NHMRC) of Australia
Organisation Unit: University of the Sunshine Coast, Queensland; School of Health and Behavioural Sciences - Legacy
Language: English
Record Identifier: 99629434102621
Output Type: Journal article

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