Background: Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by widespread inflammation and multi-organ involvement. Cannabis, noted for its anti-inflammatory and immunomodulatory properties, has gained attention for its potential role in autoimmune disease management. However, its role in disease outcomes, such as organ-specific complications and inflammation markers, is poorly understood, necessitating further investigation.

Objectives: To compare clinical outcomes in SLE patients with cannabis-related disorders against those without, evaluating endpoints such as all-cause mortality, major adverse cardiac events (MACE), lupus nephritis, neuropsychiatric complications, and inflammatory markers.

Methods: This retrospective analysis utilized TriNetX data, using 137 healthcare organizations, to define two cohorts: SLE patients with cannabis use (N = 7,826) and without cannabis use (N = 272,097). Propensity score matching balanced 16 demographic, clinical, and medication variables, yielding 7,826 patients per cohort. Outcomes assessed included major adverse cardiovascular events (MACE), lupus nephritis, neuropsychiatric complications such as seizure and psychosis, all-cause mortality, and laboratory markers (ESR, CRP, anti-DsDNA). Key demographic variables included age, gender, and ethnicity. Risk ratios, odds ratios, and survival analyses were computed within a 10-year follow-up window. Comparative statistical methods evaluated differences across matched cohorts to identify cannabis’ impact on SLE-related outcomes.

Results: Post-matching results had a mean age of 46 years, were 77% female, and 45% White. Among included patients, cannabis users had a 38.5% higher all-cause mortality risk (7.6% vs. 5.5%; RR: 1.385, p<0.001) and lower survival probability at 10 years (78% vs. 84%). MACE was slightly higher among cannabis users (10.5% vs. 8.2%; RR: 1.289, p<0.001). Neuropsychiatric complications were more prevalent in cannabis users (7.7% vs. 3.5%; RR: 2.206, p<0.001). Conversely, lupus nephritis risk was significantly lower in cannabis users (6.8% vs. 8.5%; RR: 0.803, p=0.001). Cannabis users also showed elevated mean inflammatory markers for both ESR (33.4 vs. 29.0, p<0.001) and CRP (24.6 vs. 19.3, p<0.001), while anti-DsDNA levels showed no significant difference. Across all outcomes, 8,680 patients (52%) from the cannabis cohort and 18,343 patients (65%) from the non-cannabis cohort were excluded due to outcomes occurring prior to the analysis period.

Conclusion: This study underscores the complex role of cannabis in systemic lupus erythematosus (SLE). While cannabis may help reduce chronic pain intensity, its use was associated with increased neuropsychiatric risks, cardiovascular events, higher mortality, and elevated inflammatory markers. Conversely, cannabis was linked to a lower risk of lupus nephritis, suggesting potential nephroprotective benefits. With the rise of recreational cannabis use, it is vital to weigh these potential benefits against the significant risks. We see that in most cases the primary driver of cannabis use in SLE is pain management, a debilitating symptom in this population. Physicians should engage in thoughtful discussions with patients, balancing cannabis’ role in chronic pain relief with its possible adverse effects. Further research is needed to explore these findings, providing clearer guidance for safe and effective cannabis use in autoimmune disease management and addressing its growing use in clinical and recreational contexts.

REFERENCES: NIL.

Acknowledgements: NIL.

Disclosure of Interests: None declared.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.