Cannabinoids and their effects on pain physiology
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The document discusses the endocannabinoid system and its role in pain physiology. It summarizes evidence from animal experiments showing that cannabinoids have analgesic effects by reducing inflammatory mediators and modulating brain regions involved in pain processing. Evidence from human experiments also suggests cannabinoids can reduce pain unpleasantness and brain region connectivity associated with chronic pain, as well as play a role in placebo analgesia for both opioids and non-opioids. However, the clinical evidence for cannabinoids reducing pain is still considered weak.
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Cannabinoids and their effects on pain physiology
- 1. Cannabinoids and their effects on pain physiology Peter Kamerman Brain Function Research Group, School of Physiology, University of the Witwatersrand PainSA Congress 2021 Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License
- 4. CB receptor affinity CB1 CB2 D9-tetrahydrocannabinol (THC) 2-arachidonoyl glycerol (2-AG) Anandamide (AEA) Cannabidiol (CBD)
- 5. Pain: Supra-spinal distribution of CB receptors RVM PAG Amygdala PFC Thalamus CB1 (neuronal) CB2 (microglia) Finn et al. PAIN 162 (supplement 1): S5-S25, 2021. DOI: 10.1097/j.pain.0000000000002268
- 6. Pain: Spinal and peripheral distribution of CB receptors Peripheral nerve endings DRG Dorsal horn CB1 (neuronal) CB2 (microglia) CB2 (neuronal) Finn et al. PAIN 162 (supplement 1): S5-S25, 2021. DOI: 10.1097/j.pain.0000000000002268
- 8. Fisher et al. PAIN 162 (supplement 1): S45-S66, 2021. DOI: 10.1097/j.pain.0000000000001929 Evidence from clinical studies Effect size (Hedge’s g standardised mean differences) Proportion of placebo group with ≥30% pain reduction Proportion of cannabinoid group with ≥30% pain reduction Sample size
- 9. Presidential Task Force on Cannabis and Cannabinoid Analgesia PAIN 162 (supplement 1): S1-S2, 2021. DOI: 10.1097/j.pain.0000000000002265
- 10. Soliman et al. PAIN 162 (supplement 1): S26-S44, 2021. DOI: 10.1097/j.pain.0000000000002269 Evidence from animal studies Effect size (Hedge’s g standardised mean differences) Mean = 1.32
- 11. Presidential Task Force on Cannabis and Cannabinoid Analgesia PAIN 162 (supplement 1): S1-S2, 2021. DOI: 10.1097/j.pain.0000000000002265
- 12. Data from animal experiments
- 13. Maldonado et al. PAIN 157 (supplement 1): S23-S32, 2016. DOI: 10.1097/j.pain.0000000000000428 Summary: Data from animal experiments
- 14. Data from human experiments
- 15. Cencioni et al. PLoS 5: e8688, 2010. DOI: 10.1371/journal.pone.0008688 Peripheral: Inhibition of inflammation INF-gamma TNF-alpha
- 16. Weizman et al. Neurology 91: e1285-e1294, 2018. DOI: 10.1212/WNL.0000000000006293 Supraspinal: Reduced brain region connectivity 15 men, chronic radicular neuropathic pain N = 9 N = 6
- 17. Weizman et al. Neurology 91: e1285-e1294, 2018. DOI: 10.1212/WNL.0000000000006293 Supraspinal: Reduced brain region connectivity Error bars = standard errors of the mean
- 18. Weizman et al. Neurology 91: e1285-e1294, 2018. DOI: 10.1212/WNL.0000000000006293 Supraspinal: Reduced brain region connectivity Connectivity between anterior cingulate cortex and secondary somatosensory cortex
- 19. Lee et al. PAIN 154: 124–134, 2013. DOI: 10.1016/j.pain.2012.09.017 Supraspinal: Reduced pain unpleasantness THC Sensitised Placebo Sensitised THC No sensitisation Placebo No sensitisation Capsaicin (1% cream) Control (placebo cream) Randomised order Agent State 15 healthy men
- 20. Lee et al. PAIN 154: 124–134, 2013. DOI: 10.1016/j.pain.2012.09.017 Supraspinal: Reduced pain unpleasantness Error bars = standard errors of the mean THC Placebo
- 21. Lee et al. PAIN 154: 124–134, 2013. DOI: 10.1016/j.pain.2012.09.017 Supraspinal: Reduced pain unpleasantness Error bars = standard errors of the mean
- 22. Lee et al. PAIN 154: 124–134, 2013. DOI: 10.1016/j.pain.2012.09.017 Supraspinal: Reduced pain unpleasantness
- 23. Opioid placebo analgesia Benedetti et al. Nature Medicine 17:1228-1230, 2011. DOI: 10.1038/nm.2435 Day 1 (torniquet) No intervention No intervention Day 2 (torniquet) Morphine Morphine Day 3 (torniquet) Morphine Morphine Day 4 (torniquet) Placebo Placebo + Rimonabant (CBR inhibitor) Analgesic response to morphine Analgesic response to placebo
- 24. Opioid placebo analgesia Benedetti et al. Nature Medicine 17:1228-1230, 2011. DOI: 10.1038/nm.2435
- 25. Non-opioid placebo analgesia Benedetti et al. Nature Medicine 17:1228-1230, 2011. DOI: 10.1038/nm.2435 Day 1 (torniquet) No intervention No intervention Day 2 (torniquet) Ketorolac Ketorolac Day 3 (torniquet) Ketorolac Ketorolac Day 4 (torniquet) Placebo Placebo + Rimonabant (CBR inhibitor) Analgesic response to ketorolac Analgesic response to placebo
- 26. Non-opioid placebo analgesia Benedetti et al. Nature Medicine 17:1228-1230, 2011. DOI: 10.1038/nm.2435
- 27. Conclusion • Clinical evidence is weak • Animal data indicates functional relationship • Human experimental data for a weak effect