St John's wort is one of the few herbal medicines that has been subjected to controlled studies in order to determine the significance of its interaction with numerous drugs. Although this can be reassuring, the clinical significance of many interactions is still unpredictable because of the variable chemical composition of products.
It is important to note that interactions due to CYP and P-gp induction do not appear significant with low hyperforin extracts (ZE 117).
Clinical note— Mechanisms responsible for reported interactions
Based on the herb's pharmacology, there are several mechanisms by which it may interact with drugs. Considering SJW has significant serotonin reuptake inhibitor activity and significantly upregulates both 5-HT1Aand 5-HT2A receptors, concomitant use of drugs that elevate serotonin levels, such as tricyclic antidepressants or SSRIs, may result in additive or synergistic effects and increase the risk of serotonergic syndrome. As the constituent hyperforin has a significant and selective induction effect on CYP3A4 and 2C19 activity (Durr et al 2000, Wang et al 2001) and induces the drug transporter P-glycoprotein, a number of pharmacokinetic interactions are possible with those drugs that are substrates for CYP3A4 or 2C19 and/or rely on P-gp transport. Refer to Chapter 8 for further information on interactions with herbs and natural supplements._i
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