Despite advances in treatment of glioblastomas (GBMs), the median survival remains 14-16 months. In the United States, 52.5 million people ≥12 years of age used cannabis in 2021. We aim to elucidate differences in complications after craniotomy for resection of GBM between users and nonusers of cannabis. Merative MarketScan Research Data (2008-2019) (includes >265 million patients) were used to extract adults (≥18 years of age) with GBM diagnosis (International Classification of Diseases-9 code 191.x and International Classification of Diseases-10 code C71.x) who had a craniotomy (Current Procedure Terminology code 61510) from inpatient admission data. The inverse probability treatment weighted analysis balanced the groups of cannabis abuse disorder (CAD) and no CAD in terms of age, gender, insurance coverage, comorbidities, and prior 12-month opioid dependence. Individuals with CAD were younger (median, 37 vs. 51 years; P < 0.0001). There was a lower percentage of women (19% vs. 45%; P < 0.0001). In the CAD group, opioid abuse pattern for ≥12 months was higher (16% vs. 5%; P=0.001) and the rate of complications was higher (32% vs. 15%; P= 0.001) during index hospital stay. At 6 months postdischarge, neurologic complications were higher among the CAD group (27% vs. 8%; P < 0.001). At 1 year postdischarge, patients with CAD sought feweroutpatient services (P= 0.012). More neurologic complications were seen in the CAD group (31% vs. 12%; P< 0.001). This retrospective population-based study sounds a higher rate of neurologic complications among patients using cannabis who also had a newly diagnosed GBM. This suggests the lack of a protective effect from use of cannabis in patients with primary malignant brain tumors.