A systematic review and meta-analysis of cannabis-based medicines, cannabinoids and endocannabinoid system modulators tested for antinociceptive effects in animal models of injury-related or pathological persistent pain.
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Author(s)
Type
Journal Article
Abstract
ABSTRACT: We report a systematic review and meta-analysis of studies which assessed the antinociceptive efficacy of cannabinoids, cannabis-based medicines, and endocannabinoid system modulators on pain-associated behavioural outcomes in animal models of pathological or injury-related persistent pain. In April 2019, we systematically searched 3 online databases and used crowd science and machine learning to identify studies for inclusion. We calculated a standardised mean difference (SMD) effect size for each comparison and performed a random effects meta-analysis. We assessed the impact of study design characteristics and reporting of mitigations to reduce the risk of bias. We meta-analysed 374 studies in which 171 interventions were assessed for antinociceptive efficacy in rodent models of pathological or injury-related pain. Most experiments were conducted in male animals (86 %). Antinociceptive efficacy was most frequently measured by attenuation of hypersensitivity to evoked limb withdrawal. Selective CB1, CB2, non-selective cannabinoid receptor agonists (including delta-9-tetrahydrocannabinol; THC), and PPAR-alpha agonists (predominantly palmitoylethanolamide; PEA) significantly attenuated pain-associated behaviours in a broad range of inflammatory and neuropathic pain models. Fatty acid amide hydrolase (FAAH) inhibitors, monoacylglycerol lipase (MGL) inhibitors and cannabidiol (CBD) significantly attenuated pain-associated behaviours in neuropathic pain models but yielded mixed results in inflammatory pain models. The reporting of criteria to reduce the risk of bias was low, therefore the studies have an unclear risk of bias. The value of future studies could be enhanced by improving the reporting of methodological criteria, the clinical relevance of the models and behavioural assessments. Notwithstanding, the evidence supports the hypothesis of cannabinoid-induced analgesia.
Date Issued
2021-07
Date Acceptance
2021-03-12
Citation
Pain, 2021, 162, pp.S26-S44
ISSN
0304-3959
Publisher
Elsevier
Start Page
S26
End Page
S44
Journal / Book Title
Pain
Volume
162
Copyright Statement
© 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain. This is an open access article
distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share
the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share
the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/33729209
PII: 00006396-900000000-98088
Subjects
11 Medical and Health Sciences
17 Psychology and Cognitive Sciences
Anesthesiology
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2021-03-15