Objective: Cannabis use disorder (CUD) is increasingly prevalent in the United States, yet long-term health consequences remain poorly defined. Oral cancer is plausible given shared carcinogens between cannabis and tobacco. This study assessed associations between CUD and five-year oral cancer risk in a large clinical cohort.

Methods: This retrospective cohort study analyzed clinical records from the University of California Health Data Warehouse, covering six academic medical centers. Adults screened for drug use disorders between January 2012 and December 2019 were included if they had no prior oral cancer diagnosis. The index date was the date of first screening. Patients were followed for five years for oral cancer diagnoses (lip or tongue), thereby extending data collection to December 2024. CUD was defined by a new ICD-coded diagnosis during follow-up. Logistic regression and Cox proportional hazards models estimated odds ratios (ORs), hazard ratios (HRs), and 95 % confidence intervals (CIs), adjusting for age, sex, body mass index (BMI), and smoking status.

Results: Among 45,129 eligible patients, 949 (2.1 %) developed CUD. Oral cancer incidence was 0.74 % in the CUD group and 0.23 % in non-CUD patients. CUD was associated with significantly increased risk of oral cancer (unadjusted OR 3.24; 95 % CI, 1.50–7.00). The association remained significant after adjustment (adjusted OR 3.25; 95 % CI, 1.47–7.17; adjusted HR 3.25; 95 % CI, 1.48–7.13).

Conclusions: CUD was linked to a more than threefold increase in oral cancer risk over five years. These findings highlight the need to assess long-term oncologic risks of problematic cannabis use.