Saint John's Wort (Hypericum perforatum) is an herb commonly used as an antidepressant. How it works to combat depression is currently unknown. It has been shown to increase serotonin levels. Saint John's Wort is an extremely weak MAO inhibitor, too weak to have any effect at normal doses. There is debate to whether or not Saint John's Wort acts as a serotonin reupdate inhibitor.
Cytochrome P450 Enzyme Interactions
Saint John’s Wort has been shown to dramatically interact with several medications and herbs. It affects several cytochrome P450 enzymes responsible for drug metabolism. CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4 are all affected.
|Enzyme||Interaction At High Doses||Verified In Humans|
|CYP2C19||Potent Inhibition ||?|
|CYP2E1||100% Inhibition ||?|
|CYP3A4||Weak Inhibition ||?|
|Enzyme||Interaction At Low Doses||Verified In Humans|
|CYP1A2||No effect ||?|
|CYP2C9||Potent Induction ||Yes|
|CYP2C19||Potent Induction ||Yes|
|CYP2D6||Mild Induction (No effect from hyperforin )||?|
|CYP2E1||Potent Induction ||Yes|
|CYP3A4||Potent Induction ||Yes|
One human liver hepatocyte in vitro study showed a 65% induction for CYP2E1, using low doses only. Inhibition was evident at high doses. In another study a daily intake of 900 mg St John’s wort for 28 days in humans showed an induction of CYP2E1 activity by increasing the 6-hydroxychlorzoxazone/chlorzoxazone serum ratio by nearly 30%.