The AAPS Journal

, 11:710 | Cite as

Herb–Drug Interactions with St John’s Wort (Hypericum perforatum): an Update on Clinical Observations

  • Francesca Borrelli
  • Angelo A. Izzo
Review Article Theme: Natural Products as Therapeutic Modulators


St John’s wort (SJW) extracts, prepared from the aerial parts of Hypericum perforatum, contain numerous pharmacologically active ingredients, including naphthodianthrones (e.g., hypericin and its derivatives), phloroglucinols derivatives (e.g., hyperforin, which inhibits the reuptake of a number of neurotransmitters, including serotonin), and flavonoids. Such extracts are widely used for the treatment of mild-to-moderate depression. As a monotherapy, SJW has an encouraging safety profile. However, relevant and, in some case, life-threatening interactions have been reported, particularly with drugs which are substrate of cytochrome P450 and/or P-glycoprotein. Well-documented SJW interactions include (1) reduced blood cyclosporin concentration, as suggested by multiple case reports as well as by clinical trials, (2) serotonin syndrome or lethargy when SJW was given with serotonin reuptake inhibitors, (3) unwanted pregnancies in women while using oral contraceptives and SJW, and (4) reduced plasma drug concentration of antiretroviral (e.g., indinavir, nevirapine) and anticancer (i.e., irinotecan, imatinib) drugs. Hyperforin, which is believed to contribute to the antidepressant action of St John’s wort, is also strongly suspected to be responsible of most of the described interactions.

Key words

cytochrome P450 enzymes herb–drug interactions herbal products P-glycoprotein St John’s wort 


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Copyright information

© American Association of Pharmaceutical Scientists 2009

Authors and Affiliations

  1. 1.Department of Experimental PharmacologyUniversity of Naples Federico IINaplesItaly

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