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St John's Wort - Is it an Inhibitor or Inducer for Opiates?

Altered Perception

Altered Perception

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There seems to be contradicting information regarding St John's Wort. Whilst it is known to induce CYP enzyme's and supposedly react in the opposite way grapefruit juice does with opiates the RX list has mentioned it as a substance that potentiates opiates....

http://www.rxlist.com/st_johns_wort-page3/supplements.htm
Scroll down to "Medications for pain (Narcotic drugs)"

Medications for pain (Narcotic drugs)
Interaction Rating: Major Do not take this combination.
The body breaks down some medications for pain to get rid of them. St. John's wort might decrease how fast the body gets rid of some medications for pain. By decreasing how fast the body gets rid of some medications for pain, St. John's wort might increase the effects and side effects of some medications for pain.

Some medications for pain include meperidine (Demerol), hydrocodone, morphine, oxycodone (OxyContin), and many others.
Click to expand...

On the the other hand independant research has found "Following St. John’s wort administration oxycodone plasma concentration was significantly decreased by 50% and its half-life was shortened by 27%, resulting in the self-reported drug effects of oxycodone decreasing significantly (p=0.004)"...

http://updates.pain-topics.org/2010/08/st-johns-wort-may-thwart-opioid.html

But according to the rxlist only medications interacting with the (Cytochrome P450 2C19 (CYP2C19), Cytochrome P450 3A4 (CYP3A4) substrates) are decreased in effectiveness. So how does St John's Wort Really effect Opiates? and which is the correct information ? Is it the serotonergic effects that make it unpredictable and vary outcome?
 
As I know,
Method of extraction,and part of the plants determines pharmacologic activity of Hypericum.

The stem, has MAOI activity.
The flowering bulb has SNRI action, as welll as, increasing GABA A and B.

Hyperforin is responsible for the SNRI action, but,according to one source, it doesn't cross BBB, unlike Hypericin.

Still, according to another source,they removed hypericin and hyperforin, but,still, hypericum exerts itss antidepressant effects.

I think it's complicated.

So far, hypericum (flowering top) increases the effect of Benzos, I find that it's relaxing.
I tried other product,which they crushed the whole plants, I gets agitation and restlessness. This maybe due to the combo of MAOI and SNRI action from the stem and flowering top.

When I co ingest opiates ( codeine) with hypericum, it seems that the formation of active desmethylcodeine is inhibited. Codeine,Tramadol, are prodrug, requires CYP4502D6 to convert it to active metabolites, (unlike other opiates like oxycontin,morphine etc).

Via CYP4502D6, codeine is transformed to morphine. (10%).

This is my experience with hypericum and opioid.

Moclobemide, a RIMA, potentiates the effects of opioids.
I tried it.
Paroxetine, a SSRI and any SNRI , decreases the effect of opioids.

Any other input is appreciated
 
Thanks for sharing your experience. I didn't realise something that appears to be so basic and common knowledge could in fact be so complicated, difficult to answer and prone to misconceptions.

I had this question lurking in here and in BDD for the past few days and no one could answer it, I am really suprised no one seems to know for sure.
I have a lot riding on the answer and I've even had to stop taking "hypericum" with my pain meds just until I can figure it all out. :(
 
You already answered the question in the OP. Oxycodone's half life is significantly shorter while taking St. johns wort. Rx list isn't a perfect website and they made a mistake. Common sense says that induction of the enzymes that metabolize oxycodone will result in a reduced effects.
 
Okay thank you, all I needed to know was which source made the mistake and it turns out according to you "Rxlist' was inacurrate, so thank you for answering my question.

I am suprised it took this long for somone to actually respond in the way you did, thanks again your a legend! I can finally adjust my medication accordingly :D

As for everyone else who couldnt be bothered replying... :p
 
Altered Perception, I know you already got your answer, but I didn't really see an answer in here that explicated the effects of St. John's Wort on Oxycodone, so:

Oxycodone is metabolized faster when taken in conjunction with St. John's Wort because St. John's Wort induces CYP3A4 (Oxycodone is primarily metabolized by CYP3A) as well as CYP2D6 (which Oxycodone is secondarily metabolized by).





edit: ^^^it's highly likely that St. John's Wort is in fact NOT a CYP2D6 inducer.
 
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I'm not an expert in pharmacology but to me it seems that it depends entirely on the opioid used. St. Johns Worth is NEVER an inhibitor of a CP450 enzyme. It is an inducer of CYP1A2, CYP2D6 and CYP3A4.. This means that opioids that are metabolised with this enzyme are metabolised quicker... This however doesn't necessarily mean that it will be less potent, as some metabolites are more potent then the parent compound. For oxycodone this means it'll be less potent, because the metabolites are known to be (a lot) less active then the parent compound. Codeine is metabolized to morphine by CYP2D6, so inducing the enzyme should actually potentiate codeine. Therefore, RXlist is NOT wrong.

In short: St. Johns Worth is an inducer of CP Enzymes 1A2, 2D6 and 3A4. It is never an inhibitor of CP450 enzymes. It can potentiate some opioids with metabolites more potent then the parent compound.
 
Wizzle said:
For oxycodone this means it'll be less potent, because the metabolites are known to be (a lot) less active then the parent compound.
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Well... oxycodone is O-demethylated to oxymorphone by CYP2D6. Oxymorphone is definitely more potent than oxycodone.
 
Indeed I was wrong about that, serves me right for using wiki as a source for oxycodone metabolites.. The rest still stands though.

Just a question for anyone who knows: when using St. Johns Worth for inducing CYP450 enzymes, will the increased metabolism to oxymorphone (2D6) outweigh the potency reduction caused by inducing metabolism to noroxycodone (3A4)?
 
Wizzle said:
I'm not an expert in pharmacology but to me it seems that it depends entirely on the opioid used. St. Johns Worth is NEVER an inhibitor of a CP450 enzyme. It is an inducer of CYP1A2, CYP2D6 and CYP3A4.. This means that opioids that are metabolised with this enzyme are metabolised quicker... This however doesn't necessarily mean that it will be less potent, as some metabolites are more potent then the parent compound. For oxycodone this means it'll be less potent, because the metabolites are known to be (a lot) less active then the parent compound. Codeine is metabolized to morphine by CYP2D6, so inducing the enzyme should actually potentiate codeine. Therefore, RXlist is NOT wrong.

In short: St. Johns Worth is an inducer of CP Enzymes 1A2, 2D6 and 3A4. It is never an inhibitor of CP450 enzymes. It can potentiate some opioids with metabolites more potent then the parent compound.
Click to expand...

Rxlist is wrong. They included many examples of opiates whose effects are reduced from st johns wort. Their explanation doesn't say that bioactivation is responsible for increased effects, it says the effects are increased because it takes longer for the medications to be metabolized.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1884478/

^This study also claims that SJW has no effects on CYP2D6 which is the enzyme responsible for producing morphine from codeine and oxymorphone from oxycodone. CYP3A4 was induced which is responsible for producing almost worthless metabolites.

Any way you look at, SJW will decrease the effects of most opiates metabolized by the cytochrome enzyme system. If you look at Davevanza's experience above with codeine, he noted a decrease in codeine efficacy. This has also been my personal experience with hydrocodone,oxycodone, and codeine.
 
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Although that is technically right you cannot expect such a site to be so precise.. It is made for laymen and not professionals, although they might have stated increase or decrease of effects.

Seems my table of CYP450 interactions is out-of-date though.
 
grrr8Dane said:
^^I've noticed that some CYP450 tables have conflicting information. Here's a CYP450 table that I've found to be quite accurate.
Click to expand...

Yeah it can be pretty irritating when half the stuff says one thing and half says another. The consensus seems to be 2D6 is induced less than 3A4 though at any rate.
 
^^Well in that case, If you've found anything on there to be incorrect, it'd be much appreciated if you could fill me in on what you've found to be wrong.
 
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