Abstract
The endocannabinoid system (ECS) is involved in all aspects of the pathophysiological processes of pain. The nociceptive pathway includes transduction, transmission, modulation and perception, with the ECS playing an essential role in both afferent and efferent pain stimuli. Interest in using cannabinoid products for pain is of continued research and clinical interest. Data in human, lab animals and now companion animals does show efficacy for use especially for chronic pain states. The relative therapeutic index appears favorable and the addition of these compounds at least gives veterinary practitioners another tool to consider for pain management. Careful consideration is important for product selection, not only quality but cannabinoid and terpene profiles that may best fit a patient’s pain state. The clinically relevant science of medical cannabinoids for veterinary patients is in its infancy but is very encouraging. We now have our first well conducted clinical trials with more underway. The future looks promising for medical cannabinoids, specifically CBD, for the treatment of pain conditions in our patients. Given the numerous nuances of products and the ECS dosing for pain, both acute and chronic, dosing should be done in an escalating manner. Reasonable considerations for CBD dominant or isolate products can start as low as 0.5 mg/kg by mouth twice to three times a day and increase significantly until the therapeutic benefit is appreciated.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Abdel-Salam, O. (2016). Gastric acid inhibitory and gastric protective effects of Cannabis and cannabinoids. Asian Pacific Journal of Tropical Medicine, 9(5), 413–419. https://doi.org/10.1016/j.apjtm.2016.04.021.
Alexander, S. P., & Randall, M. (2007). Cannabinoids and their actions. British Journal of Pharmacology, 152(5), 557–558. https://doi.org/10.1038/sj.bjp.0707483.
Al-Hasani, R., & Bruchas, M. (2011). Molecular mechanisms of opioid receptor-dependent signaling and behavior. Anesthesiology, 115(6), 1363–1381. https://doi.org/10.1097/aln.0b013e318238bba6.
Alhouayek, M., Gouveia-Figueira, S., Hammarström, M. L., & Fowler, C. J. (2018). Involvement of CYP1B1 in interferon γ-induced alterations of epithelial barrier integrity. British Journal of Pharmacology, 175(6), 877–890. https://doi.org/10.1111/bph.14122.
Alshaarawy, O. (2019). Total and differential white blood cell count in cannabis users: Results from the cross-sectional National Health and Nutrition Examination Survey, 2005–2016. Journal of Cannabis Research, 1(1). https://doi.org/10.1186/s42238-019-0007-8.
Alsherbiny, M., & Li, C. (2018). Medicinal cannabis—Potential drug interactions. Medicine, 6(1), 3. https://doi.org/10.3390/medicines6010003.
Arevalo-Martin, A., Garcia-Ovejero, D., Sierra-Palomares, Y., Paniagua-Torija, B., Gonzalez-Gil, I., Ortega-Gutierrez, S., & Molina-Holgado, E. (2012). Early endogenous activation of CB1 and CB2 receptors after spinal cord injury is a protective response involved in spontaneous recovery. PLoS One, 7(11). https://doi.org/10.1371/journal.pone.0049057.
Bakas, T., Nieuwenhuijzen, P. V., Devenish, S., Mcgregor, I., Arnold, J., & Chebib, M. (2017). The direct actions of cannabidiol and 2-arachidonoyl glycerol at GABA A receptors. Pharmacological Research, 119, 358–370. https://doi.org/10.1016/j.phrs.2017.02.022.
Banerjee, S., & McCormack, S. (2019). Medical cannabis for the treatment of chronic pain: A review of clinical effectiveness and guidelines. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health 24. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK546424/
Baron, E. P. (2018). Medicinal properties of cannabinoids, terpenes, and flavonoids in cannabis, and benefits in migraine, headache, and pain: An update on current evidence and cannabis science. Headache: The Journal of Head and Face Pain, 58(7), 1139–1186. https://doi.org/10.1111/head.13345.
Beaulieu, P. (2007). Cannabinoids for postoperative pain. Anesthesiology, 106(2), 397–397. https://doi.org/10.1097/00000542-200702000-00028.
Beaulieu, P., & Ware, M. (2007). Reassessment of the role of cannabinoids in the management of pain. Current Opinion in Anaesthesiology, 20(5), 473–477. https://doi.org/10.1097/aco.0b013e3282efd175.
Bergamaschi, M., Queiroz, R., Chagas, M., et al. (2011). Cannabidiol Reduces the Anxiety Induced by Simulated Public Speaking in Treatment-Naïve Social Phobia Patients. Neuropsychopharmacology, 36, 1219–1226. https://doi.org/10.1038/npp.2011.6.
Botting, R. M. (2000). Mechanism of action of acetaminophen: Is there a cyclooxygenase 3? Clinical Infectious Diseases, 31(Suppl_5). https://doi.org/10.1086/317520.
Bushlin, I., Gupta, A., Stockton, S. D., Miller, L. K., & Devi, L. A. (2012). Dimerization with cannabinoid receptors allosterically modulates delta opioid receptor activity during neuropathic pain. PLoS One, 7(12). https://doi.org/10.1371/journal.pone.0049789.
Cascio, C. J. (2010). Somatosensory processing in neurodevelopmental disorders. Journal of Neurodevelopmental Disorders, 2(2), 62–69. https://doi.org/10.1007/s11689-010-9046-3.
Cascio, M., Gauson, L., Stevenson, L., Ross, R., & Pertwee, R. (2009). Evidence that the plant cannabinoid cannabigerol is a highly potent α2-adrenoceptor agonist and moderately potent 5HT1A receptor antagonist. British Journal of Pharmacology, 159(1), 129–141. https://doi.org/10.1111/j.1476-5381.2009.00515.x.
Cathel, A. M., Reyes, B. A., Wang, Q., Palma, J., Mackie, K., Bockstaele, E. J., & Kirby, L. G. (2014). Cannabinoid modulation of alpha2adrenergic receptor function in rodent medial prefrontal cortex. European Journal of Neuroscience, 40(8), 3202–3214. https://doi.org/10.1111/ejn.12690.
Chen, D., Gao, M., Gao, F., Su, Q., & Wu, J. (2017). Brain cannabinoid receptor 2: Expression, function and modulation. Acta Pharmacologica Sinica, 38(3), 312–316. https://doi.org/10.1038/aps.2016.149.
Chiocchetti, R., Galiazzo, G., Tagliavia, C., Stanzani, A., Giancola, F., Menchetti, M., Militerno, G., Bernardini, C., Forni, M., & Mandrioli, L. (2019). Cellular distribution of canonical and putative cannabinoid receptors in canine cervical dorsal root ganglia. Frontiers in Veterinary Science, 6, 313. https://doi.org/10.3389/fvets.2019.00313.
Chiou, L., Hu, S. S., & Ho, Y. (2013). Targeting the cannabinoid system for pain relief? Acta Anaesthesiologica Taiwanica, 51(4), 161–170. https://doi.org/10.1016/j.aat.2013.10.004.
Curtis, M., Tan, R., Castrechini, N., Rabiee, A., & Mills, L. (2020). CannPal CPAT-01 results presentation and research abstract. Retrieved 2020, from https://www.asx.com.au/asxpdf/20190506/pdf/444vtptks9jdj5.pdf
Dhopeshwarkar, A., & Mackie, K. (2014). CB2 Cannabinoid receptors as a therapeutic target-what does the future hold? Molecular Pharmacology, 86(4), 430–437. https://doi.org/10.1124/mol.114.094649.
Du, H., Chen, X., Zhang, J., & Chen, C. (2011). Inhibition of COX-2 expression by endocannabinoid 2-arachidonoylglycerol is mediated via PPAR-γ. British Journal of Pharmacology, 163(7), 1533–1549. https://doi.org/10.1111/j.1476-5381.2011.01444.x.
Feng, Y., He, X., Yang, Y., Chao, D., Lazarus, L. H., & Xia, Y. (2012). Current research on opioid receptor function. Current Drug Targets, 13(2), 230–246. https://doi.org/10.2174/138945012799201612.
Ferrari, L. F., Lotufo, C. M., Araldi, D., Rodrigues, M. A., Macedo, L. P., Ferreira, S. H., & Parada, C. A. (2014). Inflammatory sensitization of nociceptors depends on activation of NMDA receptors in DRG satellite cells. Proceedings of the National Academy of Sciences, 111(51), 18363–18368. https://doi.org/10.1073/pnas.1420601111.
Fukuda, S., Kohsaka, H., Takayasu, A., Yokoyama, W., Miyabe, C., Miyabe, Y., Harigai, M., Miyasaka, N., & Nanki, T. (2014). Cannabinoid receptor 2 as a potential therapeutic target in rheumatoid arthritis. BMC Musculoskeletal Disorders, 15, 275. https://doi.org/10.1186/1471-2474-15-275.
Gamble, L., Boesch, J. M., Frye, C. W., Schwark, W. S., Mann, S., Wolfe, L., et al. (2018). Pharmacokinetics, safety, and clinical efficacy of cannabidiol treatment in osteoarthritic dogs. Frontiers in Veterinary Science, 5. https://doi.org/10.3389/fvets.2018.00165.
Gao, F., Zhang, L., Su, T., Li, L., Zhou, R., Peng, M., et al. (2015). Signaling mechanism of cannabinoid receptor-2 activation-induced β-endorphin release. Molecular Neurobiology, 53(6), 3616–3625. https://doi.org/10.1007/s12035-015-9291-2.
Gordon, R., Gordon, R. J., & Sofia, R. (1976). Antitussive activity of some naturally occurring cannabinoids in anesthetized cats. European Journal of Pharmacology, 35(2), 309–313. https://doi.org/10.1016/0014-2999(76)90233-8.
Guerrero-Alba, R., Barragán-Iglesias, P., González-Hernández, A., Valdez-Moráles, E. E., Granados-Soto, V., Condés-Lara, M., et al. (2019). Some prospective alternatives for treating pain: The endocannabinoid system and its putative receptors GPR18 and GPR55. Frontiers in Pharmacology, 9. https://doi.org/10.3389/fphar.2018.01496.
Gui, H., Liu, X., Liu, L., Su, D., & Dai, S. (2015). Activation of cannabinoid receptor 2 attenuates synovitis and joint destruction in collagen-induced arthritis. Immunobiology, 220(6), 817–822. https://doi.org/10.1016/j.imbio.2014.12.012.
Guindon, J., & Hohmann, A. (2009). The endocannabinoid system and pain. CNS & Neurological Disorders Drug Targets, 8(6), 403–421. https://doi.org/10.2174/187152709789824660.
Gyires, K., & Zádori, Z. S. (2016). Role of cannabinoids in gastrointestinal mucosal defense and inflammation. Current Neuropharmacology, 14(8), 935–951. https://doi.org/10.2174/1570159x14666160303110150.
Hama, A., & Sagen, J. (2011). Activation of spinal and supraspinal cannabinoid-1 receptors leads to antinociception in a rat model of neuropathic spinal cord injury pain. Brain Research, 1412, 44–54. https://doi.org/10.1016/j.brainres.2011.07.031.
Hill, M. N., Hunter, R. G., & McEwen, B. S. (2009). Chronic stress differentially regulates cannabinoid CB1 receptor binding in distinct hippocampal subfields. European Journal of Pharmacology, 614(1-3), 66–69. https://doi.org/10.1016/j.ejphar.2009.04.048.
Hirvonen, J., Goodwin, R. S., Li, C., Terry, G. E., Zoghbi, S. S., Morse, C., et al. (2011). Reversible and regionally selective downregulation of brain cannabinoid CB1 receptors in chronic daily cannabis smokers. Molecular Psychiatry, 17(6), 642–649. https://doi.org/10.1038/mp.2011.82.
Hohmann, A. G., & Suplita, R. L., II. (2006). Endocannabinoid mechanisms of pain modulation. The AAPS Journal, 8(4), E693–E708. https://doi.org/10.1208/aapsj080479.
Holdcroft, A., Smith, M., Jacklin, A., Hodgson, H., Smith, B., Newton, M., & Evans, F. (1997). Pain relief with oral cannabinoids in familial Mediterranean fever. Anaesthesia, 52(5), 483–486. https://doi.org/10.1111/j.1365-2044.1997.139-az0132.x.
Hossain, M. Z., Ando, H., Unno, S., & Kitagawa, J. (2020). Targeting peripherally restricted cannabinoid receptor 1, cannabinoid receptor 2, and endocannabinoid-degrading enzymes for the treatment of neuropathic pain including neuropathic orofacial pain. International Journal of Molecular Sciences, 21(4), 1423. https://doi.org/10.3390/ijms21041423.
Hudson, R., Renard, J., Norris, C., Rushlow, W. J., & Laviolette, S. R. (2019). Cannabidiol counteracts the psychotropic side-effects of δ-9-tetrahydrocannabinol in the ventral hippocampus through bidirectional control of ERK1–2 phosphorylation. The Journal of Neuroscience, 39(44), 8762–8777. https://doi.org/10.1523/jneurosci.0708-19.2019.
Ibrahim, M. M., Porreca, F., Lai, J., Albrecht, P. J., Rice, F. L., Khodorova, A., et al. (2005). CB2 cannabinoid receptor activation produces antinociception by stimulating peripheral release of endogenous opioids. Proceedings of the National Academy of Sciences, 102(8), 3093–3098. https://doi.org/10.1073/pnas.0409888102.
Ibrahim, M. M., Rude, M. L., Stagg, N. J., Mata, H. P., Lai, J., Vanderah, T. W., et al. (2006). CB2 cannabinoid receptor mediation of antinociception. Pain, 122(1), 36–42. https://doi.org/10.1016/j.pain.2005.12.018.
Ishiguro, H., Leonard, C. M., Sgro, S., & Onaivi, E. S. (2013). Cannabinoid receptor gene variations in neuropsychiatric disorders. In Endocannabinoids: Molecular, pharmacological, behavioral and clinical features (pp. 3–24). https://doi.org/10.2174/9781608050284113010006.
Johnson, J. R., Burnell-Nugent, M., Lossignol, D., Ganae-Motan, E. D., Potts, R., & Fallon, M. T. (2010). Multicenter, double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of THC:CBD extract and THC extract in patients with intractable cancer-related pain. Journal of Pain and Symptom Management, 39(2), 167–179. https://doi.org/10.1016/j.jpainsymman.2009.06.008.
Kanju, P., Chen, Y., Lee, W., Yeo, M., Lee, S. H., Romac, J., Shahid, R., Fan, P., Gooden, D. M., Simon, S. A., Spasojevic, I., Mook, R. A., Liddle, R. A., Guilak, F., & Liedtke, W. B. (2016). Small molecule dual-inhibitors of TRPV4 and TRPA1 for attenuation of inflammation and pain. Scientific Reports, 6, 26894. https://doi.org/10.1038/srep26894.
Kano, M. (2014). Control of synaptic function by endocannabinoid-mediated retrograde signaling. Proceedings of the Japan Academy, Series B, 90(7), 235–250. https://doi.org/10.2183/pjab.90.235.
Kathmann, M., Flau, K., Redmer, A., Tränkle, C., & Schlicker, E. (2006). Cannabidiol is an allosteric modulator at mu- and delta-opioid receptors. Naunyn-Schmiedeberg’s Archives of Pharmacology, 372(5), 354–361. https://doi.org/10.1007/s00210-006-0033-x.
Katia, B. (2015). Interactions of the opioid and cannabinoid systems in reward: Insights from knockout studies. Frontiers in Pharmacology, 6. https://doi.org/10.3389/fphar.2015.00006.
Khasabova, I. A., Khasabov, S., Paz, J., Harding-Rose, C., Simone, D. A., & Seybold, V. S. (2012). Cannabinoid type-1 receptor reduces pain and neurotoxicity produced by chemotherapy. Journal of Neuroscience, 32(20), 7091–7101. https://doi.org/10.1523/jneurosci.0403-12.2012.
Kim, T. E., Townsend, R. K., Branch, C. L., Romero-Sandoval, E. A., & Hsu, W. (2020). Cannabinoids in the treatment of back pain. Neurosurgery, 87(2), 166–175. https://doi.org/10.1093/neuros/nyz573.
Klinger-Gratz, P. P, Ralvenius, W. T., Neumann, E., Kato, A., Nyilas, R., Lele, Z., Katona, I., Zeilhofer, H. U. (2018, January 10). Acetaminophen relieves inflammatory pain through CB1 cannabinoid receptors in the rostral ventromedial medulla. Journal of Neuroscience, 38(2), 322–334. https://doi.org/10.1523/JNEUROSCI.1945-17.2017. Epub 2017 Nov 22. PMID: 29167401; PMCID: PMC6596108.
Kogan, L., Hellyer, P., & Downing, R. (2020). The use of cannabidiol-rich hemp oil extract to treat canine osteoarthritis-related pain: A pilot study. Journal of the American Holistic Veterinary Medical Association, 58(Spring Issue), 1–10. Retrieved from https://www.ahvma.org/wp-content/uploads/Use-of-Cannabidiol-Rich-Hemp-Oil-Sample-Article.pdf
Kogan, L., Hellyer, P., & Robinson, N. (2016). Consumers’ perceptions of hemp products for animals. Journal of the American Holistic Veterinary Medical Association, 42(Spring Issue), 40–48. Retrieved from https://www.ahvma.org/wp-content/uploads/AHVMA-2016-V42-Hemp-Article.pdf
Kozak, K. R., Gupta, R. A., Moody, J. S., Ji, C., Boeglin, W. E., Dubois, R. N., et al. (2002). 15-Lipoxygenase metabolism of 2-arachidonylglycerol. Journal of Biological Chemistry, 277(26), 23278–23286. https://doi.org/10.1074/jbc.m201084200.
Kumar, S. S., Dass, L. L., & Sharma, A. K. (2010). Cannabis indica(bhang) extract as preanaesthetic to propofol anaesthesia in dogs. Journal of Applied Animal Research, 37(1), 125–127. https://doi.org/10.1080/09712119.2010.9707109.
Labuda, C. J., Koblish, M., & Little, P. J. (2005). Cannabinoid CB2 receptor agonist activity in the hindpaw incision. European Journal of Pharmacology, 527(1–3), 172–174. https://doi.org/10.1016/j.ejphar.2005.10.020.
Lehto, S., Guo, W., Malmberg, A., Huang, M., Cheng, Y., Tomlinson, S., et al. (2008). CB2 agonists reduce carrageenan-induced thermal hyperalgesia and edema in mice via a non-CB2 receptor mechanism. The Journal of Pain, 9(4), 28. https://doi.org/10.1016/j.jpain.2008.01.132.
Lester, K. J., Coleman, J. R., Roberts, S., Keers, R., Breen, G., Bögels, S., Creswell, C., Hudson, J. L., McKinnon, A., Nauta, M., Rapee, R. M., Schneider, S., Silverman, W. K., Thastum, M., Waite, P., Wergeland, G. J., & Eley, T. C. (2017). Genetic variation in the endocannabinoid system and response to Cognitive Behavior Therapy for child anxiety disorders. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics: The Official Publication of the International Society of Psychiatric Genetics, 174(2), 144–155. https://doi.org/10.1002/ajmg.b.32467.
Liu, L., Lo, Y., Chen, I., & Simon, S. A. (1997). The responses of rat trigeminal ganglion neurons to capsaicin and two nonpungent vanilloid receptor agonists, olvanil and glyceryl nonamide. Journal of Neuroscience, 17, 4101–4111.
Lowin, T., Schneider, M., & Pongratz, G. (2019). Joints for joints. Current Opinion in Rheumatology, 31(3), 271–278. https://doi.org/10.1097/bor.0000000000000590.
Luszczki, J. J. (2007). Isobolographic analysis of interaction between drugs with nonparallel dose–response relationship curves: A practical application. Naunyn-Schmiedeberg’s Archives of Pharmacology, 375(2), 105–114. https://doi.org/10.1007/s00210-007-0144-z.
Maguire, D. R., & France, C. P. (2016). Interactions between cannabinoid receptor agonists and mu opioid receptor agonists in rhesus monkeys discriminating fentanyl. European Journal of Pharmacology, 784, 199–206. https://doi.org/10.1016/j.ejphar.2016.05.018.
Maione, S., Petrocellis, L. D., Novellis, V. D., Moriello, A. S., Petrosino, S., Palazzo, E., et al. (2007). Analgesic actions of N-arachidonoyl-serotonin, a fatty acid amide hydrolase inhibitor with antagonistic activity at vanilloid TRPV1 receptors. British Journal of Pharmacology, 150(6), 766–781. https://doi.org/10.1038/sj.bjp.0707145.
Malan, P. T., Ibrahim, M. M., Deng, H., Liu, Q., Mata, H. P., Vanderah, T., et al. (2001). CB2 cannabinoid receptor-mediated peripheral antinociception. Pain, 93(3), 239–245. https://doi.org/10.1016/s0304-3959(01)00321-9.
Malek, N., Popiolek-Barczyk, K., Mika, J., Przewlocka, B., & Starowicz, K. (2015). Anandamide, acting via CB2 receptors, alleviates LPS-induced neuroinflammation in rat primary microglial cultures. Neural Plasticity, 2015, 1–10. https://doi.org/10.1155/2015/130639.
Mallet, C., Dubray, C., & Dualé, C. (2016). FAAH inhibitors in the limelight, but regrettably. International Journal of Clinical Pharmacology and Therapeutics, 54(7), 498–501. https://doi.org/10.5414/CP202687.
Manzanares, J., Julian, M., & Carrascosa, A. (2006). Role of the cannabinoid system in pain control and therapeutic implications for the management of acute and chronic pain episodes. Current Neuropharmacology, 4(3), 239–257. https://doi.org/10.2174/157015906778019527.
Manzanares, J., Corchero, J., Romero, J., Fernandez-Ruiz, J. J., Ramos, J. A., & Fuentes, J. A. (1998, March 30). Chronic administration of cannabinoids regulates proenkephalin mRNA levels in selected regions of the rat brain. Brain Research. Molecular Brain Research, 55(1), 126–132. https://doi.org/10.1016/s0169-328x(97)00371-9. PMID: 9645967.
Maroon, J., & Bost, J. (2018). Review of the neurological benefits of phytocannabinoids. Surgical Neurology International, 9(1), 91. https://doi.org/10.4103/sni.sni_45_18.
Marzo, V., & Petrocellis, L. (2010). Endocannabinoids as regulators of transient receptor potential (TRP) channels: A further opportunity to develop new endocannabinoid-based therapeutic drugs. Current Medicinal Chemistry, 17(14), 1430–1449. https://doi.org/10.2174/092986710790980078.
Mazzari, S., Canella, R., Petrelli, L., Marcolongo, G., & Leon, A. (1996). N-(2-Hydroxyethyl)hexadecanamide is orally active in reducing edema formation and inflammatory hyperalgesia by down-modulating mast cell activation. European Journal of Pharmacology, 300(3), 227–236. https://doi.org/10.1016/0014-2999(96)00015-5.
Mcpartland, J. M., Duncan, M., Marzo, V. D., & Pertwee, R. G. (2015). Are cannabidiol and Δ9-tetrahydrocannabivarin negative modulators of the endocannabinoid system? A systematic review. British Journal of Pharmacology, 172(3), 737–753. https://doi.org/10.1111/bph.12944.
McPartland, J. M., Guy, G. W., & Marzo, V. D. (2014). Care and feeding of the endocannabinoid system: A systematic review of potential clinical interventions that upregulate the endocannabinoid system. PLoS One, 9(3). https://doi.org/10.1371/journal.pone.0089566.
Mejia, S., Duerr, F., & Mcgrath, S. (2019). Evaluation of the effect of cannabidiol on osteoarthritis-associated pain in dogs—A pilot study. Abstracts of the 46th Annual Conference of the Veterinary Orthopedic Society. https://doi.org/10.1055/s-0039-1692272.
Meymandi, M. S., Keyhanfar, F., Sepehri, G. R., Heravi, G., & Yazdanpanah, O. (2017). The contribution of NMDA receptors in antinociceptive effect of pregabalin: Comparison of two models of pain assessment. Anesthesiology and Pain Medicine, 7(3). https://doi.org/10.5812/aapm.14602.
Monory, K., Polack, M., Remus, A., Lutz, B., & Korte, M. (2015). Cannabinoid CB1 receptor calibrates excitatory synaptic balance in the mouse hippocampus. Journal of Neuroscience, 35(9), 3842–3850. https://doi.org/10.1523/jneurosci.3167-14.2015.
Mücke, M., Phillips, T., Radbruch, L., Petzke, F., & Häuser, W. (2018). Cannabis-based medicines for chronic neuropathic pain in adults. Cochrane Database of Systematic Reviews. https://doi.org/10.1002/14651858.cd012182.pub2.
Navarro, M., Carrera, M. R., Fratta, W., Valverde, O., Cossu, G., Fattore, L., et al. (2001). Functional interaction between opioid and cannabinoid receptors in drug self-administration. The Journal of Neuroscience, 21(14), 5344–5350. https://doi.org/10.1523/jneurosci.21-14-05344.2001.
Nguyen, J. D., Grant, Y., Kerr, T. M., Gutierrez, A., Cole, M., & Taffe, M. A. (2018). Tolerance to hypothermic and antinoceptive effects of Δ9-tetrahydrocannabinol (THC) vapor inhalation in rats. Pharmacology Biochemistry and Behavior, 172, 33–38. https://doi.org/10.1016/j.pbb.2018.07.007.
Petrosino, S., Moriello, A. S., Verde, R., Allarà, M., Imperatore, R., Ligresti, A., et al. (2019). Palmitoylethanolamide counteracts substance P-induced mast cell activation in vitro by stimulating diacylglycerol lipase activity. Journal of Neuroinflammation, 16(1). https://doi.org/10.1186/s12974-019-1671-5.
Piomelli, D. (2014). More surprises lying ahead. The endocannabinoids keep us guessing. Neuropharmacology, 76, 228–234. https://doi.org/10.1016/j.neuropharm.2013.07.026.
Quintero, G. C. (2017). Review about gabapentin misuse, interactions, contraindications and side effects. Journal of Experimental Pharmacology, 9, 13–21. https://doi.org/10.2147/jep.s124391.
Rao, V. S. N., Menezes, A. M. S., & Viana, G. S. B. (1990). Effect of myrcene on nociception in mice. Journal of Pharmacy and Pharmacology, 42, 877–878. https://doi.org/10.1111/j.2042-7158.1990.tb07046.x
Reisine, T., & Brownstein, M. J. (1994). Opioid and cannabinoid receptors. Current Opinion in Neurobiology, 4(3), 406–412. https://doi.org/10.1016/0959-4388(94)90103-1. PMID: 7919936
Rettori, E., Laurentiis, A. D., Zubilete, M. Z., Rettori, V., & Elverdin, J. C. (2012). Anti-inflammatory effect of the endocannabinoid anandamide in experimental periodontitis and stress in the rat. Neuroimmunomodulation, 19(5), 293–303. https://doi.org/10.1159/000339113.
Reynoso-Moreno, I., Najar-Guerrero, I., Escareño, N., Flores-Soto, M. E., Gertsch, J., & Viveros-Paredes, J. M. (2017). An endocannabinoid uptake inhibitor from black pepper exerts pronounced anti-inflammatory effects in mice. Journal of Agricultural and Food Chemistry, 65(43), 9435–9442. https://doi.org/10.1021/acs.jafc.7b02979.
Rice, J., & Cameron, M. (2018). Cannabinoids for treatment of MS symptoms: State of the evidence. Current Neurology and Neuroscience Reports, 18(8). https://doi.org/10.1007/s11910-018-0859-x.
Richardson, J. (2000). Cannabinoids modulate pain by multiple mechanisms of action. The Journal of Pain, 1(1), 2–14. https://doi.org/10.1016/S1526-5900(00)90082-8.
Richardson, D., Pearson, R. G., Kurian, N., Latif, M. L., Garle, M. J., Barrett, D. A., Kendall, D. A., Scammell, B. E., Reeve, A. J., & Chapman, V. (2008). Characterisation of the cannabinoid receptor system in synovial tissue and fluid in patients with osteoarthritis and rheumatoid arthritis. Arthritis Research & Therapy, 10(2), R43. https://doi.org/10.1186/ar2401.
Rodríguez-Muñoz, M., Sánchez-Blázquez, P., Merlos, M., & Garzón-Niño, J. (2016). Endocannabinoid control of glutamate NMDA receptors: The therapeutic potential and consequences of dysfunction. Oncotarget, 7(34), 55840–55862. https://doi.org/10.18632/oncotarget.10095.
Romero, T. R., Resende, L. C., Guzzo, L. S., & Duarte, I. D. (2013). CB1 and CB2 cannabinoid receptor agonists induce peripheral antinociception by activation of the endogenous noradrenergic system. Anesthesia & Analgesia, 116(2), 463–472. https://doi.org/10.1213/ane.0b013e3182707859.
Rosenbaum, T., & Simon, S. (2006). TRPV1 receptors and signal transduction. TRP Ion Channel Function in Sensory Transduction and Cellular Signaling Cascades Frontiers in Neuroscience, 69–84. https://doi.org/10.1201/9781420005844.ch5.
Ruhaak, L. R., Felth, J., Karlsson, P. C., Rafter, J. J., Verpoorte, R., & Bohlin, L. (2011). Evaluation of the cyclooxygenase inhibiting effects of six major cannabinoids isolated from Cannabis sativa. Biological & Pharmaceutical Bulletin, 34(5), 774–778. https://doi.org/10.1248/bpb.34.774.
Russo, E. (2008). Cannabinoids in the management of difficult to treat pain. Therapeutics and Clinical Risk Management, 4, 245–259. https://doi.org/10.2147/tcrm.s1928.
Russo, E. B., & Hohmann, A. G. (2012). Role of cannabinoids in pain management. In T. Deer et al. (Eds.), Comprehensive treatment of chronic pain by medical, interventional, and integrative approaches. New York, NY: Springer. https://doi.org/10.1007/978-1-4614-1560-2_18.
Scott, D. L., Wolfe, F., & Huizinga, T. W. (2010). Rheumatoid arthritis. The Lancet, 376(9746), 1094–1108. https://doi.org/10.1016/s0140-6736(10)60826-4.
Sharkey, K. A., & Wiley, J. W. (2016). The role of the endocannabinoid system in the brain–gut axis. Gastroenterology, 151(2), 252–266. https://doi.org/10.1053/j.gastro.2016.04.015.
Small-Howard, A., Shimoda, L., Adra, C., & Turner, H. (2005). Anti-inflammatory potential of CB1-mediated cAMP elevation in mast cells. Biochemical Journal, 388(2), 465–473. https://doi.org/10.1042/bj20041682.
Smith, D. R., Stanley, C. M., Foss, T., Boles, R. G., & McKernan, K. (2017). Rare genetic variants in the endocannabinoid system genes CNR1 and DAGLA are associated with neurological phenotypes in humans. PLoS One, 12(11), e0187926. https://doi.org/10.1371/journal.pone.0187926.
Starowicz, K., & Finn, D. P. (2017). Cannabinoids and pain: Sites and mechanisms of action. Cannabinoid Pharmacology Advances in Pharmacology, 437–475. https://doi.org/10.1016/bs.apha.2017.05.003.
Starowicz, K., Malek, N., & Przewlocka, B. (2013). Cannabinoid receptors and pain. Wiley Interdisciplinary Reviews: Membrane Transport and Signaling, 2(3), 121–132. https://doi.org/10.1002/wmts.83.
Takeda, S., Misawa, K., Yamamoto, I., & Watanabe, K. (2008). Cannabidiolic acid as a selective cyclooxygenase-2 inhibitory component in cannabis. Drug Metabolism and Disposition, 36(9), 1917–1921. https://doi.org/10.1124/dmd.108.020909.
Telleria-Diaz, A., Schmidt, M., Kreusch, S., Neubert, A., Schache, F., Vazquez, E., et al. (2010). Spinal antinociceptive effects of cyclooxygenase inhibition during inflammation: Involvement of prostaglandins and endocannabinoids. Pain, 148(1), 26–35. https://doi.org/10.1016/j.pain.2009.08.013.
Tham, S. M., Angus, J. A., Tudor, E. M., & Wright, C. E. (2005). Synergistic and additive interactions of the cannabinoid agonist CP55,940 with μ opioid receptor and α 2-adrenoceptor agonists in acute pain models in mice. British Journal of Pharmacology, 144(6), 875–884. https://doi.org/10.1038/sj.bjp.0706045.
Thomas, A., Baillie, G. L., Phillips, A. M., Razdan, R. K., Ross, R. A., & Pertwee, R. G. (2007). Cannabidiol displays unexpectedly high potency as an antagonist of CB1 and CB2 receptor agonists in vitro. British Journal of Pharmacology, 150(5), 613–623. https://doi.org/10.1038/sj.bjp.0707133.
Turcotte, C., Blanchet, M. R., Laviolette, M., & Flamand, N. (2016). The CB2 receptor and its role as a regulator of inflammation. Cellular and Molecular Life Sciences: CMLS, 73(23), 4449–4470. https://doi.org/10.1007/s00018-016-2300-4.
Ultenius, C., Linderoth, B., Meyerson, B. A., & Wallin, J. (2006). Spinal NMDA receptor phosphorylation correlates with the presence of neuropathic signs following peripheral nerve injury in the rat. Neuroscience Letters, 399(1–2), 85–90. https://doi.org/10.1016/j.neulet.2006.01.018.
Vanegas, H., Vazquez, E., & Tortorici, V. (2010). NSAIDs, opioids, cannabinoids and the control of pain by the central nervous system. Pharmaceuticals, 3(5), 1335–1347. https://doi.org/10.3390/ph3051335.
Verrico, C. D., Wesson, S., Konduri, V., Hofferek, C. J., Vazquez-Perez, J., Blair, E., et al. (2020). A randomized, double-blind, placebo-controlled study of daily cannabidiol for the treatment of canine osteoarthritis pain. Pain, 161(9), 2191–2202. https://doi.org/10.1097/j.pain.0000000000001896.
Vučković, S., Srebro, D., Vujović, K. S., Vučetić, Č., & Prostran, M. (2018). Cannabinoids and pain: New insights from old molecules. Frontiers in Pharmacology, 9, 1259. https://doi.org/10.3389/fphar.2018.01259.
Vuolo, F., Petronilho, F., Sonai, B., Ritter, C., Hallak, J. E., Zuardi, A. W., et al. (2015). Evaluation of serum cytokines levels and the role of cannabidiol treatment in animal model of asthma. Mediators of Inflammation, 2015, 1–5. https://doi.org/10.1155/2015/538670.
Walker, J. M., Huang, S. M., Strangman, N. M., Tsou, K., & Sanudo-Pena, M. C. (1999). Pain modulation by release of the endogenous cannabinoid anandamide. Proceedings of the National Academy of Sciences, 96(21), 12198–12203. https://doi.org/10.1073/pnas.96.21.12198.
Wallace, J. E., Kogan, L. R., Carr, E. C. J., et al. (2020). Motivations and expectations for using cannabis products to treat pain in humans and dogs: a mixed methods study. J Cannabis Res, 2, 36. https://doi.org/10.1186/s42238-020-00045-x.
Wang, Y., Gupta, M., Poonawala, T., Farooqui, M., Li, Y., Peng, F., Rao, S., Ansonoff, M., Pintar, J. E., & Gupta, K. (2017). Opioids and opioid receptors orchestrate wound repair. Translational research : The journal of laboratory and clinical medicine, 185, 13–23. https://doi.org/10.1016/j.trsl.2017.05.003.
Wei, D., Lee, D., Cox, C. D., Karsten, C. A., Peñagarikano, O., Geschwind, D. H., & Piomelli, D. (2015). Endocannabinoid signaling mediates oxytocin-driven social reward. Proceedings of the National Academy of Sciences, 112(45), 14084–14089. https://doi.org/10.1073/pnas.1509795112.
Zendulka, O., Dovrtělová, G., Nosková, K., Turjap, M., Šulcová, A., Hanuš, L., & Juřica, J. (2016). Cannabinoids and cytochrome P450 interactions. Current Drug Metabolism, 17(3), 206–226. https://doi.org/10.2174/1389200217666151210142051.
Zou, S., & Kumar, U. (2018). Cannabinoid receptors and the endocannabinoid system: Signaling and function in the central nervous system. International Journal of Molecular Sciences, 19(3), 833. https://doi.org/10.3390/ijms19030833.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2021 The Author(s), under exclusive license to Springer Nature Switzerland AG
About this chapter
Cite this chapter
Mosley, C., Gaynor, J., Cital, S., Brassard, J. (2021). Cannabinoids for Pain Management. In: Cital, S., Kramer, K., Hughston, L., Gaynor, J.S. (eds) Cannabis Therapy in Veterinary Medicine. Springer, Cham. https://doi.org/10.1007/978-3-030-68317-7_5
Download citation
DOI: https://doi.org/10.1007/978-3-030-68317-7_5
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-68316-0
Online ISBN: 978-3-030-68317-7
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)