Q: I have read that St. John's wort is a natural MAO inhibitor, although Erowid does not identify it as such. Is this herb a genuine MAOI? If so, does it produce negative interactions with psychedelics that can lead to serotonin syndrome--such as can happen when mixing a prescription MAOI with DXM or MDMA?
A: Although early analysis indicated that St. John's Wort (Hypericum perforatum) is a MAOI,1 more recent research has shown this action to be extremely weak, and the herb's antidepressant effects can not be attributed to MAO inhibition.1 There have been no reported "adverse MAOI effects" from the combination of St. John's Wort with any of the foods or drugs commonly contraindicated when taking a MAOI. However, several chemicals found in St. John's Wort are known to activate five cytochrome P450 enzymes, and the body uses cytochrome P450 enzymes to break down most pharmaceuticals. There is strong evidence that it decreases drug levels in the blood with a number of medications, reducing their effectiveness, among other possible interactions.1

St. John's Wort's method of action on mood is still a mystery. It has been shown to increase serotonin levels, but this may be accomplished via a means that is more comparable to tricyclic antidepressants than to selective serotonin reuptake inhibitors. In any case, several herbal medical texts recommend that people avoid taking St. John's Wort in conjunction with an SSRI, due to concerns about causing serotonin syndrome. For this reason, it seems prudent to also avoid, or be extremely careful when taking, recreational drugs that strongly boost serotonin--such as MDMA, MDA, etc.--while taking St. John's Wort. Thanks for bringing up this important question![/quote]