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SMJ // Article
Original Article
Pilot Cross-Sectional Study Assessing the Correlation between Marijuana Use and Rheumatoid Arthritis and Systemic Lupus Erythematosus Exacerbations
Abstract
Objective: Cannabis use is increasing among patients with autoimmune rheumatic diseases, often for symptom relief; however, its impact on disease activity remains unclear. This pilot study assessed whether cannabis use was associated with differences in flare frequency or duration among patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), or both.Methods: A cross-sectional study was conducted at a university-based rheumatology clinic in a US state where medical and recreational cannabis is legal. Adults (≥18 years) with confirmed RA, SLE, or both, receiving disease-modifying antirheumatic drug therapy for ≥3 months were included. Participants (N = 85) completed structured interviews assessing cannabis use, flare characteristics, and patient-reported outcomes. Demographics, comorbidities, substance use, and inflammatory markers also were collected.
Results: Among 85 participants (mean age 54 years; 89.4% female), 74.1% had RA, 17.6% SLE, and 8.2% had both. Cannabis use was reported by 30% of RA participants, 47% of SLE participants, and 71.4% of participants with both diagnoses. In the RA subgroup (n = 60), cannabis users had a greater odds of experiencing flares lasting longer than 3 days (odds ratio 4.4, 95% confidence interval 1.4–14.3). No association was found with RA flare frequency. Due to small sample sizes, no statistical analysis was conducted in the SLE or RA/SLE subgroups.
Conclusions: Cannabis use was associated with prolonged RA flares but not increased flare frequency. As cannabis becomes more accessible, further research is needed to clarify its immunologic effects. Clinicians should counsel patients regarding the potential risks of cannabis use in autoimmune disease management.
Posted in: Rheumatology and Orthopedics29
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References
1. Hill KP, Palastro MD, Johnson B, et al. Cannabis and pain: a clinical review. Cannabis Cannabinoid Res 2017;2:96–104.
2. Wu D, Luo Y, Li T, et al. Systemic complications of rheumatoid arthritis: focus on pathogenesis and treatment. Front Immunol 2022; 13:1051082.
3. Ameer MA, Chaudhry H, Mushtaq J, et al. An overview of systemic lupus erythematosus (SLE) pathogenesis, classification, and management. Cureus 2022;14:e30330.
4. Smiljanić Tomičević L, Barešić M, Mayer M, et al. Musculoskeletal manifestations of systemic lupus erythematosus. Acta Clin Croat 2023;62:714–723.
5. Bingham CO, Pohl C, Woodworth TG, et al. Developing a standardized definition for disease “flare” in rheumatoid arthritis (OMERACT 9 Special Interest Group). J Rheumatol 2009;36:2335–2341.
6. Ruperto N, Hanrahan LM, Alarcón GS, et al. International consensus for a definition of disease flare in lupus. Lupus 2011;20:453–462.
7. Benjamin O, Goyal A, Lappin SL. Disease-modifying antirheumatic drugs (DMARD). StatPearls NCBI Bookshelf version. StatPearls Publishing; 2025. Accessed April 22, 2025. https://www.ncbi.nlm.nih.gov/books/NBK507863/.
8. Vergne-Salle P, Pouplin S, Trouvin AP, et al. The burden of pain in rheumatoid arthritis: impact of disease activity and psychological factors. Eur J Pain 2020;24:1979–1989.
9. Kelly A, Tymms K, Tunnicliffe DJ, et al. Patients’ attitudes and experiences of disease-modifying antirheumatic drugs in rheumatoid arthritis and spondyloarthritis: a qualitative synthesis. Arthritis Care Res 2018;70:525–532.
10. Wipfler K, Simon TA, Katz P, et al. Increase in cannabis use among adults with rheumatic diseases: results from a 2014-2019 United States observational study. Arthritis Care Res 2022;74:2091–2099.
11. Leung J, Chan G, Stjepanović D, et al. Prevalence and self-reported reasons of cannabis use for medical purposes in USA and Canada. Psychopharmacology (Berl) 2022;239:1509–1519.
12. Jain N, Moorthy A. Cannabinoids in rheumatology: friend, foe or a bystander? Musculoskeletal Care 2022;20:416–428.
13. Lowin T, Schneider M, Pongratz G. Joints for joints: cannabinoids in the treatment of rheumatoid arthritis. Curr Opin Rheumatol 2019; 31:271–278.
14. National Conference of State Legislatures. State medical cannabis laws. 2025. Accessed June 14, 2025. https://www.ncsl.org/health/state-medical-cannabis-laws.
15. US Drug Enforcement Administration. Drug scheduling . 2023. Accessed June 14, 2025. https://www.dea.gov/drug-information/drug-scheduling.
16. Lefebvre È, Tawil N, Yahia L. Transdermal delivery of cannabidiol for the management of acute inflammatory pain: a comprehensive review of the literature. Int J Mol Sci 2024;25:5858.
17. Pertwee RG. The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: Δ9-tetrahydrocannabinol, cannabidiol and Δ9-tetrahydrocannabivarin. Br J Pharmacol 2008;153:199–215.
18. Mlost J, Bryk M, Starowicz K. Cannabidiol for pain treatment: focus on pharmacology and mechanism of action. Int J Mol Sci 2020;21:8870.
19. Chandra S, Radwan MM, Majumdar CG, et al. New trends in cannabis potency in USA and Europe during the last decade (2008–2017). Eur Arch Psychiatry Clin Neurosci 2019;269:5–15.
20. Mechoulam R, Parker LA. The endocannabinoid system and the brain. Annu Rev Psychol 2013;64:21–47.
21. Aletaha D, Smolen JS. Diagnosis and management of rheumatoid arthritis: a review. JAMA 2018;320:1360–1372.
22. Blake DR, Robson P, Ho M, et al. Preliminary assessment of the efficacy, tolerability and safety of a cannabis-based medicine (Sativex) in the treatment of pain caused by rheumatoid arthritis. Rheumatol (Oxford) 2006;45:50–52.
23. Richardson D, Pearson RG, Kurian N, et al. Characterisation of the cannabinoid receptor system in synovial tissue and fluid in patients with osteoarthritis and rheumatoid arthritis. Arthritis Res Ther 2008;10:R43.
24. Fechtner S, Singh AK, Srivastava I, et al. Cannabinoid receptor 2 agonist JWH-015 inhibits interleukin-1β-induced inflammation in rheumatoid arthritis synovial fibroblasts and in adjuvant induced arthritis rat via glucocorticoid receptor. Front Immunol 2019;10:1027.
25. Wang B, Kovalchuk A, Li D, et al. In search of preventive strategies: novel high-CBD Cannabis sativa extracts modulate ACE2 expression in COVID-19 gateway tissues. Aging 2020;12: 22425–22444.
26. Zhou Z, Paine MF, Spindle TR, et al. Cannabis for medical use: clinical pharmacology perspectives on scientific and regulatory challenges. Clin Pharmacol Ther 2022;111:732–735.
27. Rahaman O, Bhattacharya R, Liu CSC, et al. Cutting edge: dysregulated endocannabinoid-rheostat for plasmacytoid dendritic cell activation in a systemic lupus endophenotype. J Immunol 2019;202: 1674–1679.
28. Navarini L, Vomero M, Di Donato S, et al. 2-Arachidonoylglycerol reduces the production of interferon-gamma in T lymphocytes from patients with systemic lupus erythematosus. Biomedicines 2022;10:1675.
29. Henriquez JE, Crawford RB, Kaminski NE. Suppression of CpGODN-mediated IFNα and TNFα response in human plasmacytoid dendritic cells (pDC) by cannabinoid receptor 2 (CB2)-specific agonists. Toxicol Appl Pharmacol 2019;369:82–89.
30. Kotschenreuther K, Waqué I, Yan S, et al. Cannabinoids drive Th17 cell differentiation in patients with rheumatic autoimmune diseases. Cell Mol Immunol 2021;18:764–766.
31. Katz-Talmor D, Kivity S, Blank M, et al. Cannabidiol treatment in a murine model of systemic lupus erythematosus accelerates proteinuria development. Isr Med Assoc J 2018;20:741–745.
32. Strand NH, Maloney J, Kraus M, et al. Cannabis for the treatment of fibromyalgia: a systematic review. Biomedicines 2023;11:1621.
33. Spiera R, Hummers L, Chung L, et al. Safety and efficacy of lenabasum in a phase II, randomized, placebo-controlled trial in adults with systemic sclerosis. Arthritis Rheumatol 2020;72:1350–1360.
34. Werth VP, Hejazi E, Pena SM, et al. Safety and efficacy of lenabasum, a cannabinoid receptor type 2 agonist, in patients with dermatomyositis with refractory skin disease: a randomized clinical trial. J Invest Dermatol 2022;142:2651–2659.e1.
35. Habib G, Levinger U. Medical cannabis in treatment of resistant familial Mediterranean fever. Am J Case Rep 2019;20:1340–1342.
36. Pacher P, Steffens S, Haskó G, et al. Cardiovascular effects of marijuana and synthetic cannabinoids: the good, the bad, and the ugly. Nat Rev Cardiol 2018;15:151–166.
37. Jeffers AM, Glantz S, Byers AL, et al. Association of cannabis use with cardiovascular outcomes among US adults. J Am Heart Assoc Cardiovasc Cerebrovasc Dis 2024;13:e030178.
38. Hak AE, Karlson EW, Feskanich D, et al. Systemic lupus erythematosus and the risk of cardiovascular disease: results from the Nurses’ Health Study. Arthritis Rheum 2009;61:1396–1402.
39. Myasoedova E, Chandran A, Ilhan B, et al. The role of rheumatoid arthritis (RA) flare and cumulative burden of RA severity in the risk of cardiovascular disease. Ann Rheum Dis 2016;75:560–565.
40. Bloomfield MAP, Hindocha C, Green SF, et al. The neuropsychopharmacology of cannabis: a review of human imaging studies. Pharmacol Ther 2019;195:132–161.
41. Koppel BS, Brust JCM, Fife T, et al. Systematic review: efficacy and safety of medical marijuana in selected neurologic disorders. Neurology 2014;82:1556–1563.
42. Whiting PF, Wolff RF, Deshpande S, et al. Cannabinoids for medical use: a systematic review and meta-analysis. JAMA 2015;313: 2456–2473.
43. National Academies of Sciences. Engineering, and Medicine, Health and Medicine Division, Board on Population Health and Public Health Practice, Committee on the Health Effects of Marijuana. An evidence review and research agenda. Therapeutic effects of cannabis and cannabinoids. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. Washington, DC: The National Academies Press; 2017. Chapter 4.
44. Livne O, Shmulewitz D, Lev-Ran S, et al. DSM-5 cannabis withdrawal syndrome: demographic and clinical correlates in U.S. adults. Drug Alcohol Depend 2019;195:170–177.
45. Krebs MO, Kebir O, Jay TM. Exposure to cannabinoids can lead to persistent cognitive and psychiatric disorders. Eur J Pain 2019;23: 1225–1233.
46. Senderovich H, Meaney C, Vashishtha S. Cannabis-induced gastrointestinal tract symptoms in the adult population: a systematic review. Med Princ Pract 2024;33:90–101.
47. Ribeiro LI, Ind PW. Effect of cannabis smoking on lung function and respiratory symptoms: a structured literature review. NPJ Prim Care Respir Med 2016;26:16071.
48. Malvi A, Khatib MN, Balaraman AK, et al. Cannabis consumption and risk of asthma: a systematic review and meta-analysis. BMC Pulm Med 2025;25:48.
49. Jacquemin C, Molto A, Servy H, et al. Flares assessed weekly in patients with rheumatoid arthritis or axial spondyloarthritis and relationship with physical activity measured using a connected activity tracker: a 3-month study. RMD Open 2017; 3:e000434.
50. Rampakakis E, Thorne C, Cesta A, et al. Medical cannabis use by rheumatology patients in routine clinical care: results from The Ontario Best Practices Research Initiative. Clin Exp Rheumatol 2023;41:118–125.
