Cbd Interactions

CBD inhibits CYP3A4, CYP3A5, and P-glycoprotein, the main pathways that clear tacrolimus. A published case report documented an approximately 3-fold rise in dose-normalized tacrolimus levels after adding CBD, posing serious nephrotoxicity, neurotoxicity, and over-immunosuppression risk in transplant patients.

CBD strongly inhibits CYP2C19, the enzyme that clears N-desmethylclobazam (the active metabolite of clobazam). Co-administration triples plasma N-desmethylclobazam levels, causing excess sedation, ataxia, and somnolence; this is documented in the FDA-approved Epidiolex prescribing information.

Concomitant CBD (Epidiolex) and valproate use produces a significantly higher rate of ALT/AST elevations than either drug alone - up to ~17% of patients in the combination group versus ~1-2% on valproate alone in pooled Epidiolex trial data. Postmarketing reports also describe hyperammonemia in patients on the combination.

CBD inhibits CYP2C9 (and CYP3A4), the enzymes responsible for metabolizing the more potent S-enantiomer of warfarin. Co-use raises plasma warfarin concentrations, elevates INR, and increases bleeding risk; a published case report required a roughly 30% warfarin dose reduction after the patient started CBD.

CBD inhibits CYP2C19, an enzyme that contributes to sertraline metabolism. A published case report describes severe hyponatremia and cognitive dysfunction in a CYP2C19 intermediate metabolizer who added over-the-counter CBD to chronic sertraline, consistent with phenoconversion to a poor-metabolizer phenotype.

Simvastatin is heavily dependent on CYP3A4 for first-pass and systemic clearance, and CBD inhibits CYP3A4. Co-administration is expected to raise simvastatin and active-metabolite exposure, increasing the risk of muscle pain, transaminase elevation, and rare rhabdomyolysis.

CBD inhibits several CYP450 enzymes (notably CYP3A4, CYP2C19, CYP2C9, CYP1A2) and may modestly inhibit CYP2D6. Beta-blockers such as metoprolol, propranolol, and carvedilol are metabolized via CYP2D6 (and CYP1A2 for propranolol), so co-use can raise beta-blocker plasma levels, with additive blood-pressure lowering and bradycardia.