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  • BDD Moderators: Keif’ Richards | negrogesic

EVERY one of us should get this test done! This explains a LOT of why I struggle(d)

H

Harmredux

Bluelighter
Joined
Apr 15, 2013
Messages
163
After 10 years of wondering how my tolerance began so high and why some chemicals simply don't affect me I had my doc run the cyp450 metabolism panels. I am still looking into implications, if someone out there knows some of the definite consequences, please share. I can say that pain meds I need way more than normal just for therapeutic use and benzos don't affect me. The 2 times in my life where I tried cocaine I was told it was great by otyher people using it and it had zero effect. Same for the one time I tried dexedrine, a large dose had zero effect.
Posting the 3 out of 4 that were not normal. It seems interesting and unfortunate that on one of the abnormals I am an ultrarapid and on the other a non/poor metabolizer.
Thank God my doc knew that I am in real pain and that he treated me with respect and kindness, also thankful that I never lied to him or messed up in any other major ways.

I detoxed from alcohol (not really huge, "just" 4 seltzers a day but sometimes up to 6-7) and now after a few days of recovery after a procedure and using a lot of pain meds I am definitely going to call it quits, I will never get relief from even the large dosages I am prescribed. I think it makes sense just to deal with the pain and the resultant high blood pressure and rapid pulse rather than the constant hassle of meds and running out early because my body just doesn't process them right. If anyone catches any identifying info on the uploaded files, please shoot me a PM, I think I am good but privacy is important.

Check this out, I *think* this is a pretty unusual situation to be in. I am kind of happy to have answers though and a reason to quit for good! I think that the chances for being abnormal on one are at most like >5% but on 3, and both ends of the spectrum?! I don't know if having one abnormal meaans greater chance or if I am truly a freak.


 
I reckon I got to be on the opposite end of that then! Took me a solid 2 months on the needle to get my first habit ; my tolerance drops so fast that I've overdosed several times even on conservative amounts when resuming after a period of not using ; and even after having previously been through over five years of multiple daily use I would have to be doing it for a minimum of 3 days in a row these days to experience withdrawal symptoms. I think somebody needs to write a paper on my physiology Xd
 
What are you taking for pain and at what dosage.. share if you want because it may be interesting to see if your experience getting off them is atypical.
 
I am scripted 120mg oxy and 60mg hydro per day. To even lower bp, not pain relief, I have always needed the equivalent of 200mg oxy daily.
To control pain, about 300mg.

If I could get oxymorphone (opana), it would probably be ideal because that's what my body can't make on its own. Oxymorphone is no longer available even in generics. I called every chain pharmacy including grocery stores and tried every independent pharmacy within 50 miles. It's no longer even listed in their catalogs/vendor list of available meds. It's not on back order, iy just doesn't exist anymore.

To help with pain while I taper off I am going to ask for hydromorphone (which my body can't make on its own) which is what hydrocodone turns into.

Keep in mind that this is not just about the pain meds and benzos, many, MANY drugs including a lot used for cancer and probably 75% of the top 200 most scrioted meds I have the same problem with.

Is there something that you are suggesting I keep track of while tapering off?
 
How is this testing done, by taking a blood sample and letting it react with some reagents? I am interested in getting it but no doctor ever asked me to do it.
 
Harmredux said:
After 10 years of wondering how my tolerance began so high and why some chemicals simply don't affect me I had my doc run the cyp450 metabolism panels. I am still looking into implications, if someone out there knows some of the definite consequences, please share. I can say that pain meds I need way more than normal just for therapeutic use and benzos don't affect me. The 2 times in my life where I tried cocaine I was told it was great by otyher people using it and it had zero effect. Same for the one time I tried dexedrine, a large dose had zero effect.
Posting the 3 out of 4 that were not normal. It seems interesting and unfortunate that on one of the abnormals I am an ultrarapid and on the other a non/poor metabolizer.
Thank God my doc knew that I am in real pain and that he treated me with respect and kindness, also thankful that I never lied to him or messed up in any other major ways.

I detoxed from alcohol (not really huge, "just" 4 seltzers a day but sometimes up to 6-7) and now after a few days of recovery after a procedure and using a lot of pain meds I am definitely going to call it quits, I will never get relief from even the large dosages I am prescribed. I think it makes sense just to deal with the pain and the resultant high blood pressure and rapid pulse rather than the constant hassle of meds and running out early because my body just doesn't process them right. If anyone catches any identifying info on the uploaded files, please shoot me a PM, I think I am good but privacy is important.

Check this out, I *think* this is a pretty unusual situation to be in. I am kind of happy to have answers though and a reason to quit for good! I think that the chances for being abnormal on one are at most like >5% but on 3, and both ends of the spectrum?! I don't know if having one abnormal meaans greater chance or if I am truly a freak.


Click to expand...

I don't think your CYP450 metabolism would stop you from feeling the effects of cocaine or dexedrine.

Amphetamines are metabolized by cyp3a4 and it didn't seem like you were out of the ordinary for that.

2c19 is tramadol and other opiates so that's interesting. Is 2c19 is necessary to convert a pro drug to its actual active metabolite? Then you could get a much higher dose of the pro drug, which means certain opiates would be much more effective for you than for a non ultra rapid metabolizer.
 
You are correct about 3a4,but the interesting thing is that I *never * felt the effects from stimulants. When I was given cocaine (I have only used it twice, 20 years apart) the first time I felt nothing even though it was at a club in NYC, I was given about 2 grams the second time and it lasted weeks because I just didn't get any kind of rush or high from it.

Then there's the fact that the 2c19 is the ultrarapid and the next nearest in similarity is the poor/non metabolizer.

The biggest problem is that I am in legit pain and I can't take the pain meds responsibly because it takes so much and I end up repeating doses way too often even though I am not getting high.

I burned through a half month in a week and now I have to just wait until I am really ill to take the meds and when I am down low enough I have a couple of sub strips. I guess I could get coke to try and see if there's some analgesic effect to help me reduce the constant need for pain meds, I know for sure that I will not get addicted to it because it has been in my possession and I had no desire to rip into it and it doesn't produce obvious effects.

I am already a few weeks sober from the modest 4-7 drinks and I am stacked up with a few meds like NAC which helps restore glutathione (and also reduces cocaine craving in animal studies, not that I foresee a problem if I try that route), and I am going to see my doctor to talk about all this and get clonidine and next month maybe a single script of hydromorphone (dilaudid) which DOES affect me, but I am only going to do that if I am having any lingering WD.

I guess in a way this should be a wake up call to stop all the hassle of being physically dependent something providing almost no benefits.
I hope in a few weeks you guys never hear from me again. I finally found a scientific reason why this has gotten so out of control dose wise, and I understand now that I have no choice but to do the anti inflammatory diet, exercise, all that healthy lifestyle crap.
 
Harmredux said:
You are correct about 3a4,but the interesting thing is that I *never * felt the effects from stimulants. When I was given cocaine (I have only used it twice, 20 years apart) the first time I felt nothing even though it was at a club in NYC, I was given about 2 grams the second time and it lasted weeks because I just didn't get any kind of rush or high from it.

Then there's the fact that the 2c19 is the ultrarapid and the next nearest in similarity is the poor/non metabolizer.

The biggest problem is that I am in legit pain and I can't take the pain meds responsibly because it takes so much and I end up repeating doses way too often even though I am not getting high.

I burned through a half month in a week and now I have to just wait until I am really ill to take the meds and when I am down low enough I have a couple of sub strips. I guess I could get coke to try and see if there's some analgesic effect to help me reduce the constant need for pain meds, I know for sure that I will not get addicted to it because it has been in my possession and I had no desire to rip into it and it doesn't produce obvious effects.

I am already a few weeks sober from the modest 4-7 drinks and I am stacked up with a few meds like NAC which helps restore glutathione (and also reduces cocaine craving in animal studies, not that I foresee a problem if I try that route), and I am going to see my doctor to talk about all this and get clonidine and next month maybe a single script of hydromorphone (dilaudid) which DOES affect me, but I am only going to do that if I am having any lingering WD.

I guess in a way this should be a wake up call to stop all the hassle of being physically dependent something providing almost no benefits.
I hope in a few weeks you guys never hear from me again. I finally found a scientific reason why this has gotten so out of control dose wise, and I understand now that I have no choice but to do the anti inflammatory diet, exercise, all that healthy lifestyle crap.
Click to expand...
You should get opiates whose metabolites are more analgesic than the parent compound.

That way being an ultra rapid 2c 19 metabolizer would be in your favor.
 
Exactly right - but that's really only oxymorphone and hydromorphone and you can't get opana (or generic oxymorphone) anymore.

My doc will give me hydromorphone and I am going to have to just try and figure out how to keep my blood pressure and pulse from getting dangerously high when I am in pain.

Save the hydromorphone for when it's basically an emergency and just hope I can work for another 4-5 years with this pain constantly in the background. I can't work if the bp is dangerous on top of the pain.

And I am really worried about the other meds I can't use like a lot of cancer meds, literally hundreds of different meds for different conditions are metabolized by the things messed up in me.

Trying to stay positive and tell myself that being super healthy will replace the energy I have had to put into dealing with scripts
 
By the way, it was in fact a simple blood test. If you want the clinical codes to give to your provider I will find them for you. It took 2 weeks to get the results.
Does anyone know how rare it is to have both poor/non metabolizer AND ultrarapid metabolizer? I feel like either they must go hand in hand or it must be exceedingly rare, not sure which.
 
Harmredux said:
By the way, it was in fact a simple blood test. If you want the clinical codes to give to your provider I will find them for you. It took 2 weeks to get the results.
Does anyone know how rare it is to have both poor/non metabolizer AND ultrarapid metabolizer? I feel like either they must go hand in hand or it must be exceedingly rare, not sure which.
Click to expand...
There could be a range of reasons for being a poor metabolizer. Either you could have a mutation which affects the activity of the protein, or its stability (as either mRNA or protein), or a stop codon early in the sequence, making a truncated protein.

All of these mutations are similar because they affect the structure of the protein. You could also have mutations on the promoter region of the gene, causing a lower copy number each time the gene is transcribed.

For rapid metabolizer phenotypes, mutations to the enzyme structure are rare. Most enzymes are fairly optimized for their specific functions, and a random mutation will have a larger likeliehood of impairing function than of improving it.

Rapid metabolizers typically have mutated promoters which recruit the transcription machinery very efficiently. Sometimes duplications of entire gene occur, where 2 copies of the protein are produced each time the gene is transcribed.

The gene for CYP3A4 is on chromasome 7 near a handful of other CYP enzymes. However CYP2C19 is located on chromasome 10, making it unlikely that these alterations in enzyme function were produced by a shared initiating event.

As to how rare this is, it depends on your ethnicity. Different alleles have different frequencies in different geographical areas.

Figure 1 in the paper linked below shows pie charts of the major mutations in common cyp enzymes across the different continents.

www.ncbi.nlm.nih.gov

Worldwide Distribution of Cytochrome P450 Alleles: A Meta‐analysis of Population‐scale Sequencing Projects

Genetic polymorphisms in cytochrome P450 (CYP) genes can result in altered metabolic activity toward a plethora of clinically important medications. Thus, single nucleotide variants and copy number variations in CYP genes are major determinants of drug ...
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
 
Harmredux said:
Exactly right - but that's really only oxymorphone and hydromorphone and you can't get opana (or generic oxymorphone) anymore.

My doc will give me hydromorphone and I am going to have to just try and figure out how to keep my blood pressure and pulse from getting dangerously high when I am in pain.

Save the hydromorphone for when it's basically an emergency and just hope I can work for another 4-5 years with this pain constantly in the background. I can't work if the bp is dangerous on top of the pain.

And I am really worried about the other meds I can't use like a lot of cancer meds, literally hundreds of different meds for different conditions are metabolized by the things messed up in me.

Trying to stay positive and tell myself that being super healthy will replace the energy I have had to put into dealing with scripts
Click to expand...
That’s strange about not being able to get oxymorphone anymore. I have a close friend that still gets prescribed the little green generic pills but I don’t know where you are and I totally understand if you don’t want to say.they are from amneal pharmaceuticals.
But it wouldn’t surprise me if it’s getting harder and harder to find these days or if there are certain areas that don’t have it anymore.
Good luck my fellow bluelighter.
 
Last edited:
Skorpio said:
There could be a range of reasons for being a poor metabolizer. Either you could have a mutation which affects the activity of the protein, or its stability (as either mRNA or protein), or a stop codon early in the sequence, making a truncated protein.

All of these mutations are similar because they affect the structure of the protein. You could also have mutations on the promoter region of the gene, causing a lower copy number each time the gene is transcribed.

For rapid metabolizer phenotypes, mutations to the enzyme structure are rare. Most enzymes are fairly optimized for their specific functions, and a random mutation will have a larger likeliehood of impairing function than of improving it.

Rapid metabolizers typically have mutated promoters which recruit the transcription machinery very efficiently. Sometimes duplications of entire gene occur, where 2 copies of the protein are produced each time the gene is transcribed.

The gene for CYP3A4 is on chromasome 7 near a handful of other CYP enzymes. However CYP2C19 is located on chromasome 10, making it unlikely that these alterations in enzyme function were produced by a shared initiating event.

As to how rare this is, it depends on your ethnicity. Different alleles have different frequencies in different geographical areas.

Figure 1 in the paper linked below shows pie charts of the major mutations in common cyp enzymes across the different continents.

www.ncbi.nlm.nih.gov

Worldwide Distribution of Cytochrome P450 Alleles: A Meta‐analysis of Population‐scale Sequencing Projects

Genetic polymorphisms in cytochrome P450 (CYP) genes can result in altered metabolic activity toward a plethora of clinically important medications. Thus, single nucleotide variants and copy number variations in CYP genes are major determinants of drug ...
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
Click to expand...
WOW! THANK YOU! Could I PM you about advice on how to best spend time researching this? I have 3 mutations and 1 is non-metabolizer, 2 ultrarapid, (1 is normal in the CYP450 sequence tested) .
I'm wondering if I might be of some use to some pharmocogenomics. I got most of what you relayed above and I really should see what this entails as far as future treatment.
 
Harmredux said:
WOW! THANK YOU! Could I PM you about advice on how to best spend time researching this? I have 3 mutations and 1 is non-metabolizer, 2 ultrarapid, (1 is normal in the CYP450 sequence tested) .
I'm wondering if I might be of some use to some pharmocogenomics. I got most of what you relayed above and I really should see what this entails as far as future treatment.
Click to expand...
Sure thing. My door is open
 
deadhead4lyfe89 said:
That’s strange about not being able to get oxymorphone anymore. I have a close friend that still gets prescribed the little green generic pills but I don’t know where you are and I totally understand if you don’t want to say.they are from amneal pharmaceuticals.
But it wouldn’t surprise me if it’s getting harder and harder to find these days or if there are certain areas that don’t have it anymore.
Good luck my fellow bluelighter.
Click to expand...

I thought the generic ER was still available too.

There were studies on ssri's and opiods that concluded the opiods that didnt have a prodrug were more effective.
Not sure if there is any connection there or not tbh
 
tapentadol might be an option in op's case.
In terms of analgesic effects it is relatively strong, comparable to oxycodone even if there is less euphoria

Opioids - Nucynta/Tapentadol Megathread and FAQ-All Nucynta threads will be Merged here!

Nucynta/Tapentadol Megathread and FAQ Nucynta IR, 50, 75, & 100mg tablet bottles. What is Nucynta? Nucynta, also known as Tapentadol is a Schedule II Mu opioid agonist and Norepenephrine Reuptake Inhibitor used for the treatment of moderate to severe chronic pain. It is similar to Tramadol...
bluelight.org bluelight.org
 
I wouldn’t know but it can be made from morphine, is heroin necessary step in synth idk but guess not. I think it’s more of a chemist exercise than a profitable product to be made intentionally. Tho with enough funding I think it shouldn’t be insanely hard (less hard than spider goats etc) to train microbes to shit it out. I wonder about close relatives of 6-mam that are potentially legal and active, that topic was probably chewed up as much as it could have been...
 
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