- Cytochrome P450 enzyme substrate: CYP3A4
- Action to be taken: Caution with close monitoring for signs of toxicity. Monitor quinidine concentrations; consider choosing alternate therapy
- Rationale: Buspirone is metabolized primarily by oxidation, which in vitro has been shown to be mediated by cytochrome P450 3A4. In vitro study found cannabidiol to be a potent inhibitor of CYP3A4. In a study in healthy volunteers, coadministration of buspirone (10 mg as asingle dose) with itraconazole (200 mg/day for 4 days) increased plasma buspirone concentrations (13-fold increase in C max and 19-fold increase in AUC). These pharmacokinetic interactions were accompanied by an increased incidence of side effects attributable to buspirone. If the two drugs are to be used in combination, a low dose of buspirone (eg, 2.5 mg q.d.) is recommended.
- Buspar (buspirone) package insert. Bristol-Myers Squibb Company Princeton, NJ 2010
- Yamaori S, Ebisawa J, Okushima Y, Yamamoto I, Watanabe K. Potent inhibition of human cytochrome P450 3A isoforms by cannabidiol: Role of phenolic hydroxyl groups in the resorcinol moiety. Life Sciences. 2011;88:730-736.