TY - JOUR
T1 - Systematic review and meta-analysis of cannabinoids, cannabis-based medicines, and endocannabinoid system modulators tested for antinociceptive effects in animal models of injury-related or pathological persistent pain
AU - Soliman, Nadia
AU - Haroutounian, Simon
AU - Hohmann, Andrea G.
AU - Krane, Elliot
AU - Liao, Jing
AU - Macleod, Malcolm
AU - Segelcke, Daniel
AU - Sena, Christopher
AU - Thomas, James
AU - Vollert, Jan
AU - Wever, Kimberley
AU - Alaverdyan, Harutyun
AU - Barakat, Ahmed
AU - Barthlow, Tyler
AU - Bozer, Amber L.Harris
AU - Davidson, Alexander
AU - Diaz-delCastillo, Marta
AU - Dolgorukova, Antonina
AU - Ferdousi, Mehnaz I.
AU - Healy, Catherine
AU - Hong, Simon
AU - Hopkins, Mary
AU - James, Arul
AU - Leake, Hayley B.
AU - Malewicz, Nathalie M.
AU - Mansfield, Michael
AU - Mardon, Amelia K.
AU - Mattimoe, Darragh
AU - McLoone, Daniel P.
AU - Noes-Holt, Gith
AU - Pogatzki-Zahn, Esther M.
AU - Power, Emer
AU - Pradier, Bruno
AU - Romanos-Sirakis, Eleny
AU - Segelcke, Astra
AU - Vinagre, Rafael
AU - Yanes, Julio A.
AU - Zhang, Jingwen
AU - Zhang, Xue Ying
AU - Finn, David P.
AU - Rice, Andrew S.C.
N1 - Publisher Copyright:
© 2021 Lippincott Williams and Wilkins. All rights reserved.
PY - 2021/7/1
Y1 - 2021/7/1
N2 - We report a systematic review and meta-analysis of studies that 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 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 cannabinoid type 1, cannabinoid type 2, nonselective cannabinoid receptor agonists (including delta-9-tetrahydrocannabinol) and peroxisome proliferator-activated receptor-alpha agonists (predominantly palmitoylethanolamide) significantly attenuated pain-associated behaviours in a broad range of inflammatory and neuropathic pain models. Fatty acid amide hydrolase inhibitors, monoacylglycerol lipase inhibitors, and cannabidiol 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.
AB - We report a systematic review and meta-analysis of studies that 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 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 cannabinoid type 1, cannabinoid type 2, nonselective cannabinoid receptor agonists (including delta-9-tetrahydrocannabinol) and peroxisome proliferator-activated receptor-alpha agonists (predominantly palmitoylethanolamide) significantly attenuated pain-associated behaviours in a broad range of inflammatory and neuropathic pain models. Fatty acid amide hydrolase inhibitors, monoacylglycerol lipase inhibitors, and cannabidiol 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.
KW - Animal models
KW - Cannabinoids
KW - Cannabis-based medicine
KW - Endocannabinoid system modulator
KW - Pain
KW - Preclinical
KW - Systematic review and meta-analysis
UR - http://www.scopus.com/inward/record.url?scp=85103089540&partnerID=8YFLogxK
U2 - 10.1097/j.pain.0000000000002269
DO - 10.1097/j.pain.0000000000002269
M3 - Review article
C2 - 33729209
AN - SCOPUS:85103089540
SN - 0304-3959
VL - 162
SP - S26-S44
JO - Pain
JF - Pain
ER -