Inclusion Criteria:

• Age ≥18 years.

• Radiographically suspected or confirmed high-grade glioma planned for surgical resection as part of standard clinical care.

• Able to start disulfiram at least 3 days prior to planned surgery (treatment window 3-14 days pre-op).

• In-patient status for the duration of study.

• Karnofsky Performance Status (KPS) ≥70%.

• Adequate organ function within 14 days prior to first dose:

  • ANC ≥1.5 x 10^9/L
  • Platelets ≥100 x 10^9/L
  • Hemoglobin ≥9 g/dL
  • AST/ALT ≤2.5 x ULN
  • Total bilirubin ≤1.5 x ULN (unless Gilbert syndrome, in which case <5 x ULN).

• Total bilirubin ≤1.5 x ULN (unless Gilbert syndrome, in which case <5 x ULN).

• Ability to understand and willingness to sign written informed consent.

• Willingness to avoid alcohol and alcohol-containing products during treatment and for 14 days after last dose.

Exclusion Criteria:

• Any dexamethasone (or other systemic glucocorticoid for cerebral edema) administered prior to enrollment/first dose (including outpatient or ED administration). This does not include inhalers or topical steroids.
• Imaging features that are atypical for high-grade glioma that have reasonable concern for competing differential diagnoses (e.g. PCNSL, tumefactive MS, etc.)
• Known hypersensitivity to disulfiram or thiuram derivatives.
• Active or severe hepatic disease (e.g. hepatitis, cirrhosis, known liver disease that may be exacerbated by disulfiram), or baseline liver tests above inclusion thresholds.
• Current use of metronidazole or other contraindicated interacting medications. See section 6.0; medication reconciliation for the list of medications/foods.
• Pregnant or breastfeeding. Pregnant women are excluded from the trial because the safety in pregnancy has not been established. Women who are breastfeeding are excluded from the trial because it is not known if disulfiram is present in breast milk.
• Clinically unstable neurologic status requiring immediate steroid initiation, where delaying dexamethasone for a disulfiram trial would be unsafe (investigator judgment).
• Any condition that would limit compliance with alcohol avoidance or study procedures, or that would make participation unsafe in investigator judgment.
• Subjects receiving any other investigational agents.
• Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled or unstable cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.