increasing tramadol metabolism

[wafflehead77]

I was wandering if any of the tramadol enthusiasts on this board have used a cyp3a4-inducer to enhance the metabolism of tramadol into M1.

Theoretically it should work, and since M1 is has a higher binding affinity to mu receptors, should give trams more of an opiate feel to them.

Now, this is nothing new, people have known this for a while, but has anyone tried it? I am specifically interested in hyperforin, an active ingredient in St. Johns Wart. It is not the strongest cyp3a4 inducer, but it is the most easily obtainable. All the others I have found are RX-only, and are not very common.

For those who are fluent in chemistry and pharmacokinetics/dynamics, is this substance (hyperforin/St. Johns Wart) capable of a high enough enzyme-induction to cause a significant difference in tramadol metabolism?

The only downside of this seems to be that the threshold for seizures appears to be lower, but the only indication of this I have seen pertains to carbamazepine, and may be specific to this drug interaction, and not cyp3a4 induction in general.

[SpecialGuy69]

I think you got the wrong enzyme there:

Tramadol undergoes hepatic (http://en.wikipedia.org/wiki/Hepatic) metabolism via the cytochrome P450 (http://en.wikipedia.org/wiki/Cytochrome_P450) isozyme (http://en.wikipedia.org/wiki/Isozyme) CYP2D6 (http://en.wikipedia.org/wiki/CYP2D6), being O- and N-demethylated to five different metabolites. Of these, M1 (O-Desmethyltramadol) (http://en.wikipedia.org/wiki/O-Desmethyltramadol) is the most significant since it has 200 times the μ-affinity of (+)-tramadol, and furthermore has an elimination half-life of nine hours, compared with six hours for tramadol itself.

[eveline]

Human liver microsomes catalyzed the NADPH-dependent metabolism of tramadol to the two primary tramadol metabolites, namely, O-desmethyl-tramadol (metabolite M1) and N-desmethyl-tramadol (metabolite M2). ... Tramadol was metabolized to M1 by cDNA-expressed CYP2D6 and to M2 by CYP2B6 and CYP3A4.I can't find anything on whether M2 has opioid activity. But I think making the tramadol metabolize to M2 faster would leave less to metabolize to M1. Assuming that M1 is a stronger opioid than M2, which is likely since it's the one they talk about, that's bad.

That said, I actually have tried SJW (normal dose, one 250 mg capsule) with tramadol (200 mg), I have no idea why really. I think I was thinking about the serotonergic effect, but in that case I should have been like "I *shouldn't* take these two together because of serotonin syndrome". I actually did feel like it increased the effect, but it was only a couple times so it could have been for any other reason (amount of food in my stomach or whatever)... I normally get off on tramadol anyway. So if you want to try it, be careful because of serotonin syndrome.

Oh, and as for the seizure thing: I have read that SSRIs and tricyclic antidepressants lower the seizure threshold, so it's possible SJW does too. So be careful of that too...

[nova67]

Yeah I have also heard the SJW increases the tramadols effects...but It never did anything to me...but considering the chemistry of the two...it *should* work that way....and the lowering of the seizure threshold depending on the dose you need to get high is playing with fire...I mean I would rather be able to take more and keep the seizure threshold were it is...than bring it down IMO

[wafflehead77]

I think you got the wrong enzyme there:

Yeah, I meant 2D6. 3A4 is spoken of so often that it seems to be the default cytochrome 450 enzyme my mind goes to.

Shit.

[SpecialGuy69]

Yeah, I meant 2D6. 3A4 is spoken of so often that it seems to be the default cytochrome 450 enzyme my mind goes to.

Shit. that asshole 3A4 enzyme, fuckin up my fun!