The active ingredient In St.John's Wort, is
Hypericum Perforatum and
Hyperforin Though some formulas sold as St.John's Wort do not contain Hyperforin.
St.Johns Wort's mechanism of action, from what I've read, is not entirely understood. It's thought to have weak Monoamine Oxidase Inhibitor properties, but it also effects seretonin, dopamine, and neuroepinephrine. Hypericin is thought to also activate GABA-A, GABA-B, and Glutimate Receptors.
Monoamine Oxidase Inhibitor's can be dangerous because they have potentially lethal interactions with many foods, prescription medications, OTC's, and supplement's (such as St.Johns Wort). Combining MAOI's with certain anti-depressants or serotonergic drugs, stimulants, and
certain opioids(
Tramadol, Meperidine) can cause
Seretonin Syndrome, which is a drug reaction that can be potentially lethal.
As for St.Johns' Wort, it can cause multiple drug interactions through the induction of cytochrome P450 enzyme CYP3A4 and CYP2C9, resulting in increased metabolism And decreased concentration and effect.
Buprenorphine, Methadone, Midazolam, and Alprazolam are just a few of the drugs known to have interactions with St.John's Wort. According to
this study, buprenorphine is a rather potent inhibitor of CYP2D6, while Nor-Buprenorphine, Bupe's potent full-agonist metabolite, showed weak inhibition. Some people take St.John's Wort to try and inhibit the absorption of buprenorphine in hopes that the norbuprenorphine will fill up the receptor sites instead. I've personally tried it three times. The first time I noticed no noticeable interaction, the second two times (when I was at a slightly lower dosage) I experienced a shortened duration of buprenorphine's effects, and the urge to redose out of discomfort. No high was ever experienced.
There are also studys that show that St.John's Wort Causes drug interaction through the induction of the P-Glycoprotein Efflux Transporter. This can also cause a decrease in absorption and duration in certain drugs such as methadone,
though it appears to not effect absorption or metabolism of buprenorphine.