Methadone inhibits CYP2D6, effectively potentiating itself?

[RoboRobot]

"Methadone is associated with inhibition of CYP2D6 and UGTs 2B4 and 2B7 reactions in vivo, even though it is not a substrate for these enzymes."

"Although not well recognized, methadone inhibits CYP2D6 in vivo and in vitro and UGT2B7 and 2B4 in vitro."

So, I did some searches and could not find anything on this topic here on BL.

I read two studies (well, three) stating that Methadone inhibits the Cytochrome P450 isozyme, 2D6 (CYP2D6).
(Which I quoted above.)

One study specifically mentioned the potentiation of DXM.
So, I'd like to get some feedback on these studies.

And to effectively potentiate methadone with itself, would you have to take a dose of methadone to inhibit CYP2D6, and then re-dose later after inhibited?

Sounds like how DXM inhibits it's own isozyme (enzyme) that processes DXM into DXO, which to my knowledge, is also CYP2D6.

Being prescribed methadone, I'll report later on effects of DXM and any potentiation, as I've been planning a nice dissociative vacation anyway.

Regardless, I couldn't find these studies on the forums, so I'll post the three links here that go in depth and the research done to prove how methadone inhibits CYP2D6, and also can induce greater psychological effects from DXM.

Also, I know someone was asking how to inhibit the UGT enzymes for hydromorphone on another thread, and many said there aren't a lot of OTC , if any, to do so.
I'll have to relay that information over there as well.

Regardless, these studies have some very good information, go in-depth, and prove it by phenotyping human subjects with codeine in one study, and DXM in the other, both which go through O-demethylation via CYP2D6.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3403206/ (thadone inhibits CYP2D6 and UGT2B7/2B4 in vivo: a study using codeine in methadone- and buprenorphine-maintained subjects)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1381486/ (Inhibition of human cytochrome P450 2D6 (CYP2D6) by methadone)

https://www.ncbi.nlm.nih.gov/pubmed/16089243 (Dextromethorphan-induced delirium and possible methadone interaction)

 

[Thomas29]

https://liferaftgroup.org/long-list-of-inhibitors-and-inducers-of-cyp3a4-and-cyp2d6/


ACCORDING TO THIS SOURCE METHADONE DOES INDEED Inhibit CYP2D6 Yet why does Everyone think it is OBSURD to think such a thing about Methadone?

 

[serotonin2A]

Methadone is N-demethylated by CYP2B6, CYP2C19, and CYP3A4. Because methadone is not metabolized by CYP2D6, inhibition of CYP2D6 would have no influence on its potency or biotransformation.

EDIT: I just noticed that in your post you noted that methadone is not a substrate for 2D6. If you already know that, then you would know that it wouldn't "potentiate" itself.