Tylenol #3's vs norco 10/325 for MDMA comedown

[socalrollin]

Simple question guys, I know a lot of this will be opinion but any factual info will be greatly appreciated. Which opiate would you rather have for a comedown after a huge event and a good amount of MDMA? And for those of you that really know, what one would actually work better? Thanks BL peeps!

 

[fatstep]

Well Id rather have the norco honestly, it's stronger

 

[avcpl]

Consider this from The Consequences of 3,4-Methylenedioxymethamphetamine Induced CYP2D6 Inhibition in Humans:

"It has been shown that a dose greater than 50 mg would almost completely inactivate CYP2D6 in the liver, with a dose of 100 mg almost completely inactivating CYP2D6 for up to 24 hours."


Since this is the enzyme that converts codeine into morphine, so you may not feel anything from the tylenol 3s...

It also is responsible for converting hydrocodone to hydromorphone but hydrocodone is not considered a pro-drug the way codeine is...
"Inhibition of Cytochrome P450 2D6 Metabolism of Hydrocodone to Hydromorphone Does Not Importantly Affect Abuse Liability"

 

[socalrollin]

Very interesting, I'm glad I asked. Thanks for the info so far guys. Interesting side note, I got burned on some "Molly" recently and got some rc similar to MDMA but nowhere close in reality. Anyways, the comedown was like a cocaine come down so I popped what opiates I could find "t #3's" and wow it worked wonders. Helped me relax and slowed my heart rate, also increased my mood drastically. I didn't expect this from a lil codeine considering my opiate tolerance. I was surprised with their effectiveness to say the least. I don't really even like codeine, I prefer any other opiate to be honest.

 

[futura2012]

"It has been shown that a dose greater than 50 mg would almost completely inactivate CYP2D6 in the liver, with a dose of 100 mg almost completely inactivating CYP2D6 for up to 24 hours."

Is that in regards to MDMA you mean avcpl or in regards to the opiate?

 

[avcpl]

^that is in regards to MDMA inactivating the enzyme CYP2D6 which would then affect the metabolism of the opiate...

 

[futura2012]

It inhibits the enzyme but doesnt inactivate it. CYP2D6 is needed to metabolize MDMA if it inactivated it then MDMA would be very toxic.

An example of this is when you combine Piperazine and MDMA the enzyme gets heavily inhibited and you get intoxicated.

Where did you find the evidence to suggest it becomes inactive after 50mG?

 

[avcpl]

It inhibits the enzyme but doesnt inactivate it. CYP2D6 is needed to metabolize MDMA if it inactivated it then MDMA would be very toxic.

An example of this is when you combine Piperazine and MDMA the enzyme gets heavily inhibited and you get intoxicated.

Where did you find the evidence to suggest it becomes inactive after 50mG?

MDMA indeed inhibits it's own metabolism and much is eventually excreted unmetabolized. 2D6 is not the only enzyme involved though.

http://www.erowid.org/references/texts/show/382docid345

then scroll down to page 108 and look at figure 2.

As you can see on the graphs at the 150mg dose even at the 10 hour mark(!) blood concentrations of MDMA are still higher than they are at the peak of the 100mg dose! That is why I no longer redose, there is no point--take 150mg and you will have all the MDMA in your blood you could possibly need!

And why do you think unmetabolized MDMA is so neurotoxic? consider this:

"These data demonstrate that MDMA when injected directly into the brain produces 5-HT release but no neurotoxicity, suggesting that it must be metabolised peripherally in order to produce compounds that induce free radical formation and neurotoxicity in the brain."

http://www.ncbi.nlm.nih.gov/pubmed/11351932

I said where I got the quote, it's in the post! Here is a link and another quote:

http://www.maps.org/w3pb/new/2008/2008_O_23051_1.pdf

"The observation in vivo that MDMA inhibits its own metabolism has been explained by quasi-irreversible mechanism-based inhibition (MBI) of CYP2D6, as characterized in vitro"

Here is another paper with several relevant studies summarized:

http://www.maps.org/research/mdma/protocol/review2.pdf

 

[futura2012]

MDMA indeed inhibits it's own metabolism and most is eventually excreted unmetabolized

I always assumed the drug had to be metabolized to be broken down and stop its action.

2D6 is not the only enzyme involved though.

Agreed but seems to be the most prominent involved with the metabolization of MDMA. Your second link seems to report this is not the case. I read mixed reports about this.

The observation in vivo that MDMA inhibits its own metabolism has been explained by quasi-irreversible mechanism-based inhibition (MBI) of CYP2D6, as characterized in vitro

I dont totally understand this sentence but isnt inhibition different to inactivation.

Ive done a bit of research on bzp > MDMA and everyting points at double inhibition of CYP2D6 being the cause of the intoxication by MDMA and bzp.

http://www.4shared.com/folder/s3K-05dx/MDMA_BZP_Research.html

 

[avcpl]

I always assumed the drug had to be metabolized to be broken down and stop its action.

No, not with MDMA. Likely due to receptor down-regulation and serotonin depletion I would imagine. Again, that's why it's pointless to re-dose (unless you have taken a fairly small dose initially) and pointless to take high doses (above 150mg)--even when the blood is saturated with MDMA the response curve is the same. My wife and I did an experiment (actually she wasn't aware!) and she redosed and I did not (taking a chance my roll would end before hers), but both ended the same time anyway (this was with approx. 130mg initial dose).

I dont totally understand this sentence but isnt inhibition different to inactivation.

Ive done a bit of research on bzp > MDMA and everyting points at double inhibition of CYP2D6 being the cause of the intoxication by MDMA and bzp.

I'm not sure what you don't understand. The MDMA metabolism is inhibited because one of the enzymes in it's metabolism (2D6) is inactivated.

I don't know about BZP, but there does not appear to be any link between 2D6 inhibition and neurotoxicity as evidenced by poor metabolizers (those who genetically lack the enzyme)