Buprenorphine and St John's Wort:
I've heard contradictory reports about the interaction between St John's Wort and buprenorphine. I haven't seen any direct research into interactions b/w St. John's Wort and buprenorphine, there has been quite a bit of research into the effects of St John's Wort on the CYP enzymes. The majority of clinical reports indicate that SJW increases the activity of CYP3A4 enzyme and reduces plasma concentrations of certain drugs. Although the inductive effect of SJW on CYP3A4 is clear, other reports indicate that SJW may have, to a small degree, some enzyme
inhibitory effects.
One study seeking to measure both found that acute administration of SJW
inhibited CYP3A4 activity, but with chronic exposure, the
inductive effect of SJW on enzymes predominated.
Buprenorphine is metabolised into the active metabolite norbuprenorphine primarily by CYP3A4 (also CYP2C8, and to a lesser degree 3A5 and 3A7, seem to be involved). Buprenorphine and norbuprenorphine are primarily deactivated by UGT1A1, UGT1A3 and UGT2B7. I do not know if St John's Wort affects those enzymes? There is also a high interindividual variability in metabolism of bupe and the specific metabolic path.
If it's true that acute administration of SJW inhibits CYP3A4 and chronic administration induces CYP3A4, then that would mean taking SJW occasionally or beginning to take it should lessen norbuprenorphine and taking it long-term should increase norbupe.
There is also a TON of confusion and misinformation on drug forums about the effect of SJW on enzymes and the effect of enzymes on bupe (for example a quick search turned up lots of people claiming CYP3A4 is responsible for
deactivating bupe/removing bupe from the body - which is incorrect).
I have read many anecdotal reports of SJW bringing on withdrawals in people who are on bupe or making their bupe wear off faster.
For example, in another thread znegative said:
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.
As for the other drug's you're taking and the possibility of serotonin syndrome:
So, you are talking about combining SJW, bupe and bupropion (Wellbutrin), while having recently been taking fluoxetine (Prozac), but you would be stopping it just before starting the SJW?
This study found that SJW decreased the half-life of hydroxybupropion and decreased the plasma concentrations of bupropion, probably mainly by increasing the clearance of bupropion.
Bupropion has also been suggested to be able to cause serotonin syndrome when taken with other serotonergic drugs, and there are a few case reports, however as there is no evidence that bupropion has any significant serotonergic activity it is thought that serotonin syndrome is unlikely and extremely rare.
As for the fluoxetine, I have heard of people stopping it one day and starting SJW the next with no problems, however a doctor said that since there are potential risks (serotonin syndrome, side effects) from combining fluoxetine and SJW and fluoxetine takes a long time to clear from your system it is advisable to leave at least a two-week gap between the two.
. . . . .
In addition to all this, because SJW is known to have various effects on enzymes and drugs, stopping the SJW or it wearing off could potentially create adverse opposite effects as well.
TLDR: The risk of serotonin syndrome seems relatively low but the best idea is to talk to your doctor. There is also a risk that the SJW will make the buprenorphine and the bupropion less effective.
