Purpose of the review
Pain is a prevailing symptom in osteoarthritis (OA) and greatly impacts quality of life. Pain-relieving strategies over thousands of years have included opioids and cannabinoids but require critical evaluation of efficacy and risks in this twenty-first century. This review will examine the most up-to-date evidence for use of these two categories of drugs.
Contrary to the previous concept that opioids would be advantageous for OA, the emerging evidence for true efficacy and overwhelming risks strongly supports recommendation against use. In contrast, cannabinoids, especially in the form of herbal cannabis, have been aggressively touted by advocacy, the media, and industry as an ideal and potentially less harmful panacea for many medical conditions, including relief of pain. There is currently absence of any sound study for effect of cannabinoids in management of pain associated with OA.
In this era of uncertainty about cannabinoids, rheumatologists must exercise extreme caution in counseling patients and emphasize the potential but largely unknown risks for those with OA wishing to use cannabis. Therefore, at this time, opioids in particular, and likely also cannabinoids, should only be considered for the rare patient with severe OA where suffering is extreme and surgical options are unavailable or too high risk.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
References and Recommended Reading
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
Mandl LA. Osteoarthritis year in review 2018: clinical. Osteoarthr Cartil. 2019;27(3):359–64.
Felson DT, Lawrence RC, Dieppe PA, Hirsch R, Helmick CG, Jordan JM, et al. Osteoarthritis: new insights. Part 1: the disease and its risk factors. Ann Intern Med. 2000;133(8):635–46.
Global Burden of Disease Study, C., Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990–2013: A systematic analysis for the global burden of disease study 2013. Lancet, 2015 386(9995): p. 743–800.
• Taha S, Maloney-Hall B, Buxton J. Lessons learned from the opioid crisis across the pillars of the Canadian drugs and substances strategy. Subst Abuse Treat Prev Policy. 2019;14(1):32 Recent review assessing the extent and response to the opioid crisis in Canada in recent years.
Desai RJ, et al. Association of geography and access to health care providers with long-term prescription opioid use in Medicare patients with severe osteoarthritis: a cohort study. Arthritis Rheumatol. 2019;71(5):712–21.
Disease GBD, Injury I, Prevalence C, Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017. A systematic analysis for the global burden of disease study 2017. Lancet. 2018;392(10159):1789–858.
Scott CEH, MacDonald DJ, Howie CR. 'Worse than death' and waiting for a joint arthroplasty. Bone Joint J. 2019;101-B(8):941–50.
Zhao X, et al. Clinical, humanistic, and economic burden of osteoarthritis among noninstitutionalized adults in the United States. Osteoarthr Cartil. 2019.
Swain S, et al. Comorbidities in osteoarthritis: a systematic review and meta-analysis of observational studies. Arthritis Care Res (Hoboken). 2019.
Tsuji T, Nakata K, Vietri J, Jaffe DH. The added burden of depression in patients with osteoarthritis in Japan. Clinicoecon Outcomes Res. 2019;11:411–21.
Mantyh PW. Mechanisms that drive bone pain across the lifespan. Br J Clin Pharmacol. 2019;85(6):1103–13.
O'Neill TW, Felson DT. Mechanisms of osteoarthritis (OA) pain. Curr Osteoporos Rep. 2018;16(5):611–6.
Brummett CM, et al. Characteristics of fibromyalgia independently predict poorer long-term analgesic outcomes following total knee and hip arthroplasty. Arthritis Rheumatol. 2015;67(5):1386–94.
Barr AJ, et al. A systematic review of the relationship between subchondral bone features, pain and structural pathology in peripheral joint osteoarthritis. Arthritis Res Ther. 2015;17:228.
Hill CL, Hunter DJ, Niu J, Clancy M, Guermazi A, Genant H, et al. Synovitis detected on magnetic resonance imaging and its relation to pain and cartilage loss in knee osteoarthritis. Ann Rheum Dis. 2007;66(12):1599–603.
Davis J, Eaton CB, Lo GH, Lu B, Price LL, McAlindon T, et al. Knee symptoms among adults at risk for accelerated knee osteoarthritis: data from the osteoarthritis initiative. Clin Rheumatol. 2017;36(5):1083–9.
McAlindon TE, et al. Effect of intra-articular triamcinolone vs saline on knee cartilage volume and pain in patients with knee osteoarthritis: a randomized clinical trial. Jama. 2017;317(19):1967–75.
Schaefert R, Welsch P, Klose P, Sommer C, Petzke F, Häuser W. Opioids in chronic osteoarthritis pain. A systematic review and meta-analysis of efficacy, tolerability and safety in randomized placebo-controlled studies of at least 4 weeks duration. Schmerz. 2015;29(1):47–59.
• Leopoldino AO, et al. Paracetamol versus placebo for knee and hip osteoarthritis. Cochrane Database Syst Rev. 2019;2:Cd013273 Recent systematic review including 10 RCTs demonstrating only minimal improvement in pain and function with aceteminophen use in patients with hip or knee osteoarthritis.
Deveza LA, Hunter DJ, Van Spil WE. Too much opioid, too much harm. Osteoarthr Cartil. 2018;26(3):293–5.
Atiquzzaman M, et al. Role of non-steroidal anti-inflammatory drugs (NSAIDs) in the association between osteoarthritis and cardiovascular diseases: a longitudinal study. Arthritis Rheumatol. 2019.
Ogourtsova T, Kalaba M, Gelinas I, Korner-Bitensky N, Ware MA. Cannabis use and driving-related performance in young recreational users: a within-subject randomized clinical trial. CMAJ Open. 2018;6(4):E453–62.
Faryar KA, Kohlbeck SA, Schreiber SJ. Shift in drug vs alcohol prevalence in Milwaukee County motor vehicle decedents, 2010-2016. WMJ. 2018;117(1):24–8.
Trescot AM, Datta S, Lee M, Hansen H. Opioid pharmacology. Pain Physician. 2008;11(2 Suppl):S133–53.
Mercadante S, et al. Opioid switching from and to tapentadol extended release in cancer patients: conversion ratio with other opioids. Curr Med Res Opin. 2013;29(6):661–6.
Aweid O, Haider Z, Saed A, Kalairajah Y. Treatment modalities for hip and knee osteoarthritis: a systematic review of safety. J Orthop Surg. 2018;26(3):2309499018808669.
Mu A, Weinberg E, Moulin DE, Clarke H. Pharmacologic management of chronic neuropathic pain: review of the Canadian Pain Society consensus statement. Can Fam Physician. 2017;63(11):844–52.
Hartrick CT, Rozek RJ. Tapentadol in pain management: a mu-opioid receptor agonist and noradrenaline reuptake inhibitor. CNS Drugs. 2011;25(5):359–70.
Lauche R, et al. Opioids in chronic noncancer pain-are opioids different? A systematic review and meta-analysis of efficacy, tolerability and safety in randomized head-to-head comparisons of opioids of at least four week's duration. Schmerz. 2015;29(1):73–84.
Elkader A, Sproule B. Buprenorphine: clinical pharmacokinetics in the treatment of opioid dependence. Clin Pharmacokinet. 2005;44(7):661–80.
da Costa BR, et al. Oral or transdermal opioids for osteoarthritis of the knee or hip. Cochrane Database Syst Rev. 2014;9:CD003115.
Toupin April K, et al. Tramadol for osteoarthritis. Cochrane Database Syst Rev. 2019;5:Cd005522.
Smith SR, Deshpande BR, Collins JE, Katz JN, Losina E. Comparative pain reduction of oral non-steroidal anti-inflammatory drugs and opioids for knee osteoarthritis: systematic analytic review. Osteoarthr Cartil. 2016;24(6):962–72.
• Krebs EE, Gravely A, Nugent S, Jensen AC, DeRonne B, Goldsmith ES, et al. Effect of opioid vs nonopioid medications on pain-related function in patients with chronic back pain or hip or knee osteoarthritis pain: the SPACE randomized clinical trial. JAMA. 2018;319(9):872–82. A pragmatic, 12 month randomized trial in patients with knee or hip OA or moderate to severe chronic back pain found that opioids were not superior to non-opioid medications for pain-related function, but were associated with more adverse effects.
Hochberg MC, Altman RD, April KT, Benkhalti M, Guyatt G, McGowan J, et al. American College of Rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee. Arthritis care & research. 2012;64(4):465–74.
•• Bannuru RR, et al. OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis. Osteoarthritis Cartilage. 2019; Accepted manuscript for new Osteoarthritis Research Society Internal (OARSI) guidelines for the management of osteoarthritis recommending against the use of opiates.
Sullivan MD, Howe CQ. Opioid therapy for chronic pain in the United States: promises and perils. Pain. 2013;154(Suppl 1):S94–100.
•• Fuggle N, et al. Safety of Opioids in Osteoarthritis: Outcomes of a Systematic Review and Meta-Analysis. Drugs Aging. 2019;36(Suppl 1):129–43 Recent Systematic review and meta-analysis including 17 papers highlighting significant adverse reactions associated with opioid use including constipation, nausea and neurocognitive effects.
Barbour KE, Sagawa N, Boudreau RM, Winger ME, Cauley JA, Nevitt MC, et al. Knee osteoarthritis and the risk of medically treated injurious falls among older adults: a community-based US cohort study. Arthritis Care Res (Hoboken). 2019;71(7):865–74.
Lo-Ciganic WH, Floden L, Lee JK, Ashbeck EL, Zhou L, Chinthammit C, et al. Analgesic use and risk of recurrent falls in participants with or at risk of knee osteoarthritis: data from the osteoarthritis initiative. Osteoarthr Cartil. 2017;25(9):1390–8.
Beswick AD, Wylde V, Gooberman-Hill R, Blom A, Dieppe P. What proportion of patients report long-term pain after total hip or knee replacement for osteoarthritis? A systematic review of prospective studies in unselected patients. BMJ Open. 2012;2(1):e000435.
Ben-Ari A, Chansky H, Rozet I. Preoperative opioid use is associated with early revision after total knee arthroplasty: a study of male patients treated in the veterans affairs system. JBJS. 2017;99(1):1–9.
Driesman A, Kaplan D, Feng JE, Waren DP, Vigdorchik J, Meere P, et al. Tramadol in knee osteoarthritis: does preoperative use affect patient-reported outcomes after total knee arthroplasty? J Arthroplast. 2019;34(8):1662–6.
Smith SR, Bido J, Collins JE, Yang H, Katz JN, Losina E. Impact of preoperative opioid use on total knee arthroplasty outcomes. J Bone Joint Surg Am. 2017;99(10):803–8.
•• Zeng C, et al. Association of Tramadol With All-Cause Mortality Among Patients With Osteoarthritis. JAMA. 2019;321(10):969–82 Cohort study demonstrating an increase all-cause mortality within 1 year after initial prescription with tramadol and codeine compared to 5 NSAIDs in osteoarthritis patients.
Gilmartin-Thomas JF, Bell JS, Liew D, Arnold CA, Buchbinder R, Chapman C, et al. Chronic pain medication management of older populations: key points from a national conference and innovative opportunities for pharmacy practice. Res Social Adm Pharm. 2019;15(2):207–13.
Volkow ND, McLellan AT. Opioid abuse in chronic pain—misconceptions and mitigation strategies. N Engl J Med. 2016;374(13):1253–63.
Stoicea N, Costa A, Periel L, Uribe A, Weaver T, Bergese SD. Current perspectives on the opioid crisis in the US healthcare system: a comprehensive literature review. Medicine (Baltimore). 2019;98(20):e15425.
Alkabbani W, et al. Persistence of use of prescribed cannabinoid medicines in Manitoba, Canada: A population-based cohort study. Addiction. 2019.
Government of Canada. Information for Health Care Professionals: Cannabis (marihuana, marijuana) and the cannabinoids. 2019, July 15; Available from: https://www.canada.ca/en/health-canada/services/drugs-medication/cannabis/information-medical-practitioners/information-health-care-professionals-cannabis-cannabinoids.html#a4.8.
Blake DR, Robson P, Ho M, Jubb RW, McCabe C. Preliminary assessment of the efficacy, tolerability and safety of a cannabis-based medicine (Sativex) in the treatment of pain caused by rheumatoid arthritis. Rheumatology. 2006;45(1):50–2.
Berman P, Futoran K, Lewitus GM, Mukha D, Benami M, Shlomi T, et al. A new ESI-LC/MS approach for comprehensive metabolic profiling of phytocannabinoids in Cannabis. Sci Rep. 2018;8(1):14280.
Ware MA, et al. Cannabis for the management of pain: assessment of safety study (COMPASS). J Pain. 2015;16(12):1233–42.
Ware MA, Fitzcharles MA, Joseph L, Shir Y. The effects of nabilone on sleep in fibromyalgia: results of a randomized controlled trial. Anesth Analg. 2010;110(2):604–10.
Swift W, Gates P, Dillon P. Survey of Australians using cannabis for medical purposes. Harm Reduct J. 2005;2:18.
Ware MA, Adams H, Guy GW. The medicinal use of cannabis in the UK: results of a nationwide survey. Int J Clin Pract. 2005;59(3):291–5.
Skrabek RQ, Galimova L, Ethans K, Perry D. Nabilone for the treatment of pain in fibromyalgia. J Pain. 2008;9(2):164–73.
Fitzcharles MA, et al. Rheumatologists lack confidence in their knowledge of cannabinoids pertaining to the management of rheumatic complaints. BMC Musculoskelet Disord. 2014;15:258.
•• Fitzcharles MA, et al. Position statement: a pragmatic approach for medical cannabis and patients with rheumatic diseases. J Rheumatol. 2019;46(5):532–8 CRA position statement on the importance of a pragmatic discussions with patients concerning cannabinoid use in patients with rheumatic diseases emphasizing the lack of high quality evidence for use and risk for adverse effects.
Hazekamp A. The trouble with CBD oil. Med Cannabis Cannabinoids. 2018;1:65–72.
Jouanjus E, Lapeyre-Mestre M, Micallef J. Cannabis use: signal of increasing risk of serious cardiovascular disorders. J Am Heart Assoc. 2014;3(2):e000638.
• Richards JR, et al. Cannabis use and acute coronary syndrome. Clin Toxicol (Phila). 2019;57(10):831–41 Systematic review highlighting an increased risk for both acute coronary syndrome and chronic cardiovsacular disease associated with cannabis use in 29 of 33 studies included.
Curran HV, Freeman TP, Mokrysz C, Lewis DA, Morgan CJ, Parsons LH. Keep off the grass? Cannabis, cognition and addiction. Nat Rev Neurosci. 2016;17(5):293–306.
Devinsky O, Cross JH, Laux L, Marsh E, Miller I, Nabbout R, et al. Trial of cannabidiol for drug-resistant seizures in the Dravet syndrome. N Engl J Med. 2017;376(21):2011–20.
Groeneveld GJ, Martin JH. Parasitic pharmacology: a plausible mechanism of action for cannabidiol. Br J Clin Pharmacol. 2019.
Bachhuber MA, Saloner B, Cunningham CO, Barry CL. Medical cannabis laws and opioid analgesic overdose mortality in the United States, 1999-2010. JAMA Intern Med. 2014;174(10):1668–73.
Shover CL, Davis CS, Gordon SC, Humphreys K. Association between medical cannabis laws and opioid overdose mortality has reversed over time. Proc Natl Acad Sci U S A. 2019;116(26):12624–6.
Barbosa J, Faria J, Queirós O, Moreira R, Carvalho F, Dinis-Oliveira RJ. Comparative metabolism of tramadol and tapentadol: a toxicological perspective. Drug Metab Rev. 2016;48(4):577–92.
Wilson-Morkeh H, et al. Important drug interactions exist between cannabidiol oil and commonly prescribed drugs in rheumatology practice. Rheumatology. 2019.
Foster BC, Abramovici H, And CS. Harris, Cannabis and Cannabinoids: Kinetics and Interactions. Am J Med. 2019.
Busse J, Guyatt G, Carrasco A. The 2017 Canadian guideline for opioids for chronic non-cancer pain. Hamilton: McMaster University; 2017.
Conflict of interest
The authors declare that they have no conflicts of interest.
Human and animal rights and informed consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
This article is part of the Topical Collection on Osteoarthritis
About this article
Cite this article
Barbacki, A., Fitzcharles, M. Opioids and Cannabinoids for Osteoarthritis: Either, Both, or Neither. Curr Treat Options in Rheum 6, 29–44 (2020). https://doi.org/10.1007/s40674-020-00140-3
- Medicinal herbal cannabis