ADVANCES IN CANNABINOID-BASED PAIN MANAGEMENT: EFFICACY AND EVIDENCE
DOI:
https://doi.org/10.31435/ijitss.4(48).2025.4243Keywords:
Cannabinoids, Chronic Pain, Pain Management, Cannabis, THC, CBDAbstract
Introduction and Purpose: Chronic pain is a significant global health challenge, and its management is complicated by the substantial risks associated with conventional therapies such as opioids. Cannabinoids, targeting the endocannabinoid system, have been developed as effective therapeutic options. This systematic review assesses current research evidence about cannabinoid safety and effectiveness for managing various chronic pain conditions to establish their worth in modern pain management.
Main Findings: The evidence for cannabinoid efficacy is highly condition-specific. Moderate-quality evidence supports cannabinoid-based medicines for chronic neuropathic pain, demonstrating reduced pain intensity and improved sleep. The strongest evidence exists for spasticity-related pain in multiple sclerosis, for which nabiximols is an approved treatment. Key guidelines recommend that cannabinoids have no efficacy for cancer pain. There is currently no clinical evidence for providing relief of inflammatory pain, such as fibromyalgia. Evidence also supports an adjuvant role via a potential "opioid-sparing" effect. The safety profile includes moderate side effects, which include dizziness and somnolence, and does not carry the lethal respiratory depression risk associated with opioids.
Conclusion: Cannabinoids provide a new pharmacological approach, but they do not work as a universal analgesic. The existing evidence supports their utility as adjunctive therapy for certain, refractory conditions — especially neuropathic pain and MS-related spasticity. Compared to opioids, their favorable safety profile would indicate they could represent an important adjunct for multimodal pain management. More large-scale trials using standardized formulations are required to specify their exact place they hold in evidence-based care.
References
Elzahaf, R. A., Tashani, O. A., Unsworth, B. A., & Johnson, M. I. (2012). The prevalence of chronic pain with an analysis of countries with a Human Development Index less than 0.9: A systematic review without meta-analysis. Current Medical Research and Opinion, 28(7), 1221–1229. https://doi.org/10.1185/03007995.2012.703132
Breivik, H., Collett, B., Ventafridda, V., Cohen, R., & Gallacher, D. (2006). Survey of chronic pain in Europe: Prevalence, impact on daily life, and treatment. European Journal of Pain, 10(4), 287–333. https://doi.org/10.1016/j.ejpain.2005.06.009
Pitcher, M. H., Von Korff, M., Bushnell, M. C., & Porter, L. (2019). Prevalence and profile of high-impact chronic pain in the United States. The Journal of Pain, 20(2), 146–160. https://doi.org/10.1016/j.jpain.2018.08.004
World Health Organization. (1996). Cancer pain relief: With a guide to opioid availability (2nd ed.). World Health Organization.
Harirforoosh, S., Asghar, W., & Jamali, F. (2013). Adverse effects of nonsteroidal antiinflammatory drugs: An update of gastrointestinal, cardiovascular and renal complications. Journal of Pharmacy & Pharmaceutical Sciences, 16(5), 821–847. https://doi.org/10.18433/j3vw2f
Vowles, K. E., McEntee, M. L., Julnes, P. S., Frohe, T., Ney, J. P., & van der Goes, D. N. (2015). Rates of opioid misuse, abuse, and addiction in chronic pain: A systematic review and data synthesis. Pain, 156(4), 569–576. https://doi.org/10.1097/01.j.pain.0000460357.01998.f1
Pacher, P., Bátkai, S., & Kunos, G. (2006). The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacological Reviews, 58(3), 389–462. https://doi.org/10.1124/pr.58.3.2
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
Izzo, A. A., Borrelli, F., Capasso, R., Di Marzo, V., & Mechoulam, R. (2009). Non-psychotropic plant cannabinoids: New therapeutic opportunities from an ancient herb. Trends in Pharmacological Sciences, 30(10), 515–527. https://doi.org/10.1016/j.tips.2009.07.006
Russo, E. B. (2019). The case for the entourage effect and conventional breeding of clinical cannabis: No “strain,” no gain. Frontiers in Plant Science, 9, 1969. https://doi.org/10.3389/fpls.2018.01969
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, 2018(3), CD012182. https://doi.org/10.1002/14651858.CD012182.pub2
Finnerup, N. B., Attal, N., Haroutounian, S., McNicol, E., Baron, R., Dworkin, R. H., Gilron, I., Haanpää, M., Hansson, P., Jensen, T. S., Kamerman, P. R., Lund, K., Moore, A., Raja, S. N., Rice, A. S. C., Rowbotham, M., Sena, E., Siddall, P., Smith, B. H., & Wallace, M. (2015). Pharmacotherapy for neuropathic pain in adults: A systematic review and meta-analysis. The Lancet Neurology, 14(2), 162–173. https://doi.org/10.1016/S1474-4422(14)70251-0
Furlan, A. D., Sandoval, J. A., Mailis-Gagnon, A., & Tunks, E. (2006). Opioids for chronic noncancer pain: A meta-analysis of effectiveness and side effects. CMAJ, 174(11), 1589–1594. https://doi.org/10.1503/cmaj.051528
Bell, A. D., MacCallum, C., Margolese, S., Walsh, Z., Wright, P., Daeninck, P. J., Mandarino, E., Lacasse, G., Deol, J. K., de Freitas, L., St Pierre, M., Belle-Isle, L., Gagnon, M., Bevan, S., Sanchez, T., Arlt, S., Monahan-Ellison, M., O'Hara, J., Boivin, M., & Costiniuk, C. (2024). Clinical practice guidelines for cannabis and cannabinoid-based medicines in the management of chronic pain and co-occurring conditions. Cannabis and Cannabinoid Research, 9(2), 669–687. https://doi.org/10.1089/can.2021.0156
National Comprehensive Cancer Network. (2025). Adult cancer pain (Version 1.2025). https://www.nccn.org/professionals/physician_gls/pdf/pain.pdf
Braun, I. M., Bohlke, K., Roeland, E. Y., Chen, R. C., Chasen, M., Currow, D. C., Dudgeon, D., Eisenberg, E., Kuczynski, S., Ladha, H., Le, D. T., Manyam, B., Paice, J. A., Strouse, T. B., Tzafaras, E., Vo, M., & Zbuk, K. (2024). Cannabis and cannabinoids in adults with cancer: ASCO guideline. Journal of Clinical Oncology. https://doi.org/10.1200/JCO.23.02596
Häuser, W., Welsch, P., Radbruch, L., Fisher, E., Bell, R. F., & Moore, R. A. (2023). Cannabis-based medicines and medical cannabis for adults with cancer pain. Cochrane Database of Systematic Reviews, 6(6), CD014915. https://doi.org/10.1002/14651858.CD014915.pub2
Brown, J. D., & Winterstein, A. G. (2019). Potential adverse drug events and drug–drug interactions with medical and consumer cannabidiol (CBD) use. Journal of Clinical Medicine, 8(7), 989. https://doi.org/10.3390/jcm8070989
Pergam, S. A., Woodfield, M. C., Lee, C. M., Cheng, G. S., Baker, K. K., Marquis, S. R., & Fann, J. R. (2017). Cannabis use among patients at a comprehensive cancer center in a state with legalized medicinal and recreational use. Cancer, 123(22), 4488–4497. https://doi.org/10.1002/cncr.30879
Malfitano, A. M., Proto, M. C., & Bifulco, M. (2008). Cannabinoids in the management of spasticity associated with multiple sclerosis. Neuropsychiatric Disease and Treatment, 4(5), 847–853. https://doi.org/10.2147/ndt.s3208
Pryce, G., & Baker, D. (2007). Control of spasticity in a multiple sclerosis model is mediated by CB1, not CB2, cannabinoid receptors. British Journal of Pharmacology, 150(4), 519–525. https://doi.org/10.1038/sj.bjp.0707003
Russo, M., Calabrò, R. S., Naro, A., Sessa, E., Rifici, C., D'Aleo, G., Leo, A., De Luca, R., Quartarone, A., & Bramanti, P. (2015). Sativex in the management of multiple sclerosis-related spasticity: Role of the corticospinal modulation. Neural Plasticity, 2015, 656582. https://doi.org/10.1155/2015/656582
Baker, D., Pryce, G., Jackson, S. J., Bolton, C., & Giovannoni, G. (2012). The biology that underpins the therapeutic potential of cannabis-based medicines for the control of spasticity in multiple sclerosis. Multiple Sclerosis and Related Disorders, 1(2), 64–75. https://doi.org/10.1016/j.msard.2011.11.001
Chiurchiù, V., van der Stelt, M., Centonze, D., & Maccarrone, M. (2018). The endocannabinoid system and its therapeutic exploitation in multiple sclerosis: Clues for other neuroinflammatory diseases. Progress in Neurobiology, 160, 82–100. https://doi.org/10.1016/j.pneurobio.2017.10.007
Britch, S. C., Babalonis, S., & Walsh, S. L. (2021). Cannabidiol: Pharmacology and therapeutic targets. Psychopharmacology, 238(1), 9–28. https://doi.org/10.1007/s00213-020-05712-8
Whiting, P. F., Wolff, R. F., Deshpande, S., Di Nisio, M., Duffy, S., Hernandez, A. V., Keurentjes, J. C., Lang, S., Misso, K., Ryder, S., Schmidlkofer, S., Storr, M., & Kleijnen, J. (2015). Cannabinoids for medical use: A systematic review and meta-analysis. JAMA, 313(24), 2456–2473. https://doi.org/10.1001/jama.2015.6358
Novotna, A., Mares, J., Ratcliffe, S., Novakova, I., Vachova, M., Zapletalova, O., Gasperini, C., Pozzilli, C., Cefaro, L., Comi, G., Rossi, P., Ambler, Z., Stelmasiak, Z., Erdmann, A., Montalban, X., Klimek, A., & Davies, P. (2011). A randomized, double-blind, placebo-controlled, parallel-group, enriched-design study of nabiximols (Sativex®) as add-on therapy in subjects with refractory spasticity caused by multiple sclerosis. European Journal of Neurology, 18(9), 1122–1131. https://doi.org/10.1111/j.1468-1331.2010.03328.x
Zajicek, J. P., Hobart, J. C., Slade, A., Barnes, D., & Mattison, P. G. (2012). Multiple sclerosis and extract of cannabis: Results of the MUSEC trial. Journal of Neurology, Neurosurgery & Psychiatry, 83(11), 1125–1132. https://doi.org/10.1136/jnnp-2012-302468
Azadvari, M., Pourshams, M., & Rastkar, M. (2024). Cannabinoids for spasticity in patients with multiple sclerosis: A systematic review and meta-analysis. Multiple Sclerosis and Related Disorders, 86, 105658. https://doi.org/10.1016/j.msard.2024.105658
Nielsen, S., Murnion, B., Campbell, G., Young, H., & Hall, W. (2019). Cannabinoids for the treatment of spasticity. Developmental Medicine & Child Neurology, 61(6), 631–638. https://doi.org/10.1111/dmcn.14165
Andresen, S. R., Biering-Sørensen, F., Hagen, E. M., Nielsen, J. F., Bach, F. W., & Finnerup, N. B. (2017). Cannabis use in persons with traumatic spinal cord injury in Denmark. Journal of Rehabilitation Medicine, 49(2), 152–160. https://doi.org/10.2340/16501977-2105
Cardenas, D. D., & Jensen, M. P. (2006). Treatments for chronic pain in persons with spinal cord injury: A survey study. The Journal of Spinal Cord Medicine, 29(2), 109–117. https://doi.org/10.1080/10790268.2006.11753864
Fitzcharles, M. A., Baerwald, C., Ablin, J., & Häuser, W. (2016). Efficacy, tolerability and safety of cannabinoids in chronic pain associated with rheumatic diseases. Der Schmerz, 30(1), 47–61. https://doi.org/10.1007/s00482-015-0084-3
Atalay, S., Jarocka-Karpowicz, I., & Skrzydlewska, E. (2019). Antioxidative and anti-inflammatory properties of cannabidiol. Antioxidants, 9(1), 21. https://doi.org/10.3390/antiox9010021
Guillouard, M., Authier, N., Pereira, B., Soubrier, M., & Mathieu, S. (2021). Cannabis use assessment and its impact on pain in rheumatologic diseases: A systematic review and meta-analysis. Rheumatology, 60(2), 549–556. https://doi.org/10.1093/rheumatology/keaa450
Walitt, B., Klose, P., Fitzcharles, M. A., Phillips, T., & Häuser, W. (2016). Cannabinoids for fibromyalgia. Cochrane Database of Systematic Reviews, 2016(7), CD011694. https://doi.org/10.1002/14651858.CD011694.pub2
Marinelli, L., Puce, L., Mori, L., Leandri, M., Rosa, G. M., Currà, A., Fattapposta, F., & Trompetto, C. (2022). Cannabinoid effect and safety in spasticity following stroke: A double-blind randomized placebo-controlled study. Frontiers in Neurology, 13, 892165. https://doi.org/10.3389/fneur.2022.892165
Okusanya, B. O., Lott, B. E., Ehiri, J., McClelland, J., & Rosales, C. (2022). Medical cannabis for the treatment of migraine in adults: A review of the evidence. Frontiers in Neurology, 13, 871187. https://doi.org/10.3389/fneur.2022.871187
Mücke, M., Weier, M., Carter, C., Copeland, J., Degenhardt, L., Cuhls, H., Radbruch, L., Häuser, W., & Conrad, R. (2018). Systematic review and meta-analysis of cannabinoids in palliative medicine. Journal of Cachexia, Sarcopenia and Muscle, 9(2), 220–234. https://doi.org/10.1002/jcsm.12273
Chico, S. F. V., Diaz, D. A. M., & Contreras-Puentes, N. (2024). Use of cannabidiol in the treatment of drug-refractory epilepsy in children and young adults: A systematic review. Journal of Neurosciences in Rural Practice, 15(2), 203–210. https://doi.org/10.25259/JNRP_618_2023
Liu, S., He, Z., & Li, J. (2023). Long-term efficacy and adverse effects of cannabidiol in adjuvant treatment of drug-resistant epilepsy: A systematic review and meta-analysis. Therapeutic Advances in Neurological Disorders, 16, 17562864231207755. https://doi.org/10.1177/17562864231207755
Sheriff, T., O'Keeffe, M., O'Kane, C., Murphy, M., O'Brien, T., & Creagh, D. (2020). The potential role of cannabinoids in dermatology. Journal of Dermatological Treatment, 31(8), 839–845. https://doi.org/10.1080/09546634.2019.1675854
Szepietowski, J. C., Reich, A., & Szepietowski, T. (2005). Emollients with endocannabinoids in the treatment of uremic pruritus: Discussion of the therapeutic options. Therapeutic Apheresis and Dialysis, 9(3), 277–279. https://doi.org/10.1111/j.1774-9987.2005.00271.x
Maida, V., & Daeninck, P. J. (2016). A user’s guide to cannabinoid therapies in oncology. Current Oncology, 23(6), 398–406. https://doi.org/10.3747/co.23.3487
Solmi, M., De Toffol, M., Kim, J. Y., Choi, M. J., Stubbs, B., Thompson, T., Firth, J., Miola, A., Croatto, G., Baggio, F., Michelon, S., Ballan, L., Gerdle, B., Monaco, F., Simonato, P., Scocco, P., Ricca, V., Castellini, G., Fornaro, M., … Dragioti, E. (2023). Balancing risks and benefits of cannabis use: Umbrella review of meta-analyses of randomised controlled trials and observational studies. BMJ, 382, e072348. https://doi.org/10.1136/bmj-2022-072348
Pravosud, V., Lum, E., Vali, M., Cohen, B. E., Hoggatt, K. J., Byers, A. L., Austin, P. C., Walter, L. C., Hasin, D., Zaman, T., & Keyhani, S. (2025). Cannabis use among older adults. JAMA Network Open, 8(5), e2510173. https://doi.org/10.1001/jamanetworkopen.2025.10173
Marconi, A., Di Forti, M., Lewis, C. M., Murray, R. M., & Vassos, E. (2016). Meta-analysis of the association between the level of cannabis use and risk of psychosis. Schizophrenia Bulletin, 42(5), 1262–1269. https://doi.org/10.1093/schbul/sbw003
Jeddi, H. M., Busse, J. W., Sadeghirad, B., Levine, M., Zoratti, M. J., Wang, L., Noori, A., Couban, R. J., & Tarride, J. E. (2024). Cannabis for medical use versus opioids for chronic non-cancer pain: A systematic review and network meta-analysis of randomized clinical trials. BMJ Open, 14(1), e068182. https://doi.org/10.1136/bmjopen-2022-068182
Volkow, N. D., Koob, G. F., & McLellan, A. T. (2016). Neurobiologic advances from the brain disease model of addiction. The New England Journal of Medicine, 374(4), 363–371. https://doi.org/10.1056/NEJMra1511480
Dowell, D., Ragan, K. R., Jones, C. M., & Chou, R. (2022). CDC clinical practice guideline for prescribing opioids for pain — United States, 2022. MMWR Recommendations and Reports, 71(RR-3), 1–95. https://doi.org/10.15585/mmwr.rr7103a1
World Health Organization. (2018). Cannabis and cannabis resin: Critical review report (Expert Committee on Drug Dependence, Fortieth Meeting). World Health Organization. https://www.who.int/publications/m/item/cannabis-and-cannabis-resin
Nielsen, S., Sabioni, P., Trigo, J. M., Ware, M. A., Betz-Stablein, B. D., Murnion, B., Lintzeris, N., Farrell, M., Gutman, T., & Le Foll, B. (2017). Opioid-sparing effect of cannabinoids: A systematic review and meta-analysis. Neuropsychopharmacology, 42(9), 1752–1765. https://doi.org/10.1038/npp.2017.51
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