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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

Nadia Soliman, Simon Haroutounian, Andrea G Hohmann, Elliot Krane, Jing Liao, Malcolm Macleod, Daniel Segelcke, Christopher Sena, James Thomas, Jan Vollert, Kimberley Wever, Harutyun Alaverdyan, Ahmed Barakat, Tyler Barthlow, Amber L Harris Bozer, Alexander Davidson, Marta Diaz-delCastillo, Antonina Dolgorukova, Mehnaz I Ferdousi, Catherine Healy, Simon Hong, Mary Hopkins, Arul James, Hayley B Leake, Nathalie M Malewicz, Michael Mansfield, Amelia K Mardon, Darragh Mattimoe, Daniel P McLoone, Gith Noes-Holt, Esther M Pogatzki-Zahn, Emer Power, Bruno Pradier, Eleny Romanos-Sirakis, Astra Segelcke, Rafael Vinagre, Julio A Yanes, Jingwen Zhang, Xue Ying Zhang, David P Finn, Andrew S C Rice. Pain. 2021 Jul 1;162(Suppl 1):S26-S44.

Meta-analysisOther animals

Design
Meta-analysis
Subjects
374 animal studies testing 171 interventions in rodent models of pathological or injury-related persistent pain; 86% of experiments used male animals
Dose used in the study
Not stated in the abstract
Duration
Literature searched in April 2019
What was measured
Standardised mean difference effect sizes for pain-related behaviour, mainly evoked limb withdrawal hypersensitivity, with random-effects meta-analysis and assessment of study design and risk-of-bias reporting

What the authors reported

This systematic review found:

  • PPAR-alpha agonists, predominantly palmitoylethanolamide, along with CB1, CB2 and non-selective cannabinoid agonists, significantly reduced pain behaviours across inflammatory and neuropathic models.
  • FAAH inhibitors, MAGL inhibitors and cannabidiol worked in neuropathic models but gave mixed results in inflammatory models.
  • Reporting of bias-reduction criteria was low, so risk of bias was unclear.

Limits of this study

A meta-analysis of animal studies only; it cannot show effect in people. The included studies had unclear risk of bias and mostly used male animals. Several authors report industry grants, fees or patents; none named relates to PEA products.

Source

PubMed 33729209 · doi:10.1097/j.pain.0000000000002269

Entry checked against the abstract on PubMed on 2026-09-22. The dose shown is the dose the researchers used. It is not a recommendation. How to read this page.