A new retrospective cohort study using the TriNetX Global Collaborative Network has indicated that cannabis use may significantly increase the risk of uveitis and other ocular inflammatory diseases — with the strongest associations observed in posterior segment conditions. The findings, published in the Journal of Ophthalmic Inflammation and Infection, represent the largest dataset to date examining the relationship between cannabis exposure and ocular inflammation.
The study analyzed electronic health records from more than 150 healthcare organizations worldwide, identifying 1.47 million cannabis users and 3.7 million controls. After 1:1 propensity score matching — balancing age, sex, comorbidities, and demographic factors — the final cohorts included 1,156,655 patients each.
A one-year washout period ensured only incident cases of inflammatory eye disease were captured.
Cannabis users experienced a statistically and clinically significant increase in ocular inflammatory disease compared with matched controls, including iridocyclitis, panuveitis, retinal vasculitis, and choroidal degeneration.
Notably, cannabis users also had lower inflammation-free survival over time (Kaplan–Meier analysis), with cumulative survival dropping from 99.75% (controls) to 99.53% (cannabis users). Though the absolute event rate remains low, the risk increase is substantial at a population level.
The authors discuss several biologically plausible mechanisms that could explain the association:
Pro-inflammatory signaling triggered by cannabis smoke extract, including COX-2 and IL-8 upregulation.
Oxidative stress and endothelial dysfunction, particularly with inhaled cannabis — mechanisms also implicated in blood–retinal barrier compromise.
Dysregulation of the endocannabinoid system, which modulates ocular immune homeostasis; exogenous cannabinoids may alter this balance.
The study contrasts these human epidemiologic findings with preclinical CB2-activation models, which show anti-inflammatory benefit — highlighting the complexity of cannabinoid actions in vivo.
For ophthalmologists, the findings suggest cannabis use may represent an under-recognized risk factor for uveitis, especially posterior segment inflammation. In cases of “idiopathic” uveitis, cannabis history may warrant closer scrutiny and more frequent monitoring, given the higher risk of sight-threatening disease patterns such as panuveitis or retinal vasculitis.
The study provides large-scale evidence that cannabis use is associated with increased risk of multiple ocular inflammatory diseases, with the strongest signals in posterior segment pathology. As cannabis legalization expands worldwide, the findings underscore the importance of incorporating cannabis history into routine uveitis evaluation and patient counseling.
