Opioids No effects from oxycodone?

[Nofx5868]

EDIT: I think I discovered what is going on... more details in post #9

A friend of a friend is looking for some help with figuring out why he doesn't seem to get any effects from oxycodone anymore. In the past (3+ years ago), he has taken oxycodone with great results, but that is no longer the case. He has already done a fair amount of googling, but hasn't come up with anything conclusive and would like to open a dialog with some more experiences/knowledgeable people. Here is some background on him:

He regularly uses marijuana and alcohol, and has in the past used various prescription opiates (hydrocodone, oxycodone, and a few others) to good effect. He doesn't really take anything else, but probably smokes and drinks more than he should. He has recently been given some 30mg oxycodone pills that he is certain are real/legit. One of his good friends is a bit of an opiate connoisseur, and has been using the same exact pills to great effect.

This friend of a friend has tried several different methods for dosing, and has been disappointed by all of them. The issue is not tolerance, because prior to receiving his most recent batch he had not used any opiates or similar in 6+ months, and has never taken more than 5-10 pills in any given 6 month period... he thinks that just about rules out tolerance as a possibility.

First, he tried insufflating a reasonable amount, 15mg. This resulted in no effects. This guy has used opiates to good effect a few years ago, so he knows what to look for. A couple days later, he tried again, this time insufflating 30mg. This time, the only noticeable effect was nausea. A couple days later, he took 30mg orally on an empty stomach, and again, nausea was the only outcome. Meanwhile, his friend is able to insufflate 30mg at a time to great effect, even though he uses regularly and definitely has a much stronger tolerance. Finally, he has even tried plugging a couple of times, 15mg the first time then 30mg several days later. Again, these didn't produce any effects, this time not even nausea. One other note of possible interest is that relatively recently, about 6 months ago, he had some prescription cough syrup containing oxycodone and was able to use that to great effect. Also, one other thing to note is that he is not open to the idea of IVing anything.

This leads him to several questions:

1. Is it possible to prevent the good effects from occurring by taking too much? However, 15mg doesn't seems to him like an unreasonable starting place.
2. Is it possible that some sort of health problem may be preventing the oxycodone from working properly? Perhaps, for example, if this guy has unknowingly damaged his liver with alcohol, could that prevent the oxycodone from working properly? Would the liver come into account in all cases, or only when the oxycodone is taken orally? Can we rule out liver damage based on the fact that insufflation doesn't get the job done?
3. Is there anything he can do, such as taking a supplement or exercising more, that would increase the positive effects of the oxycodone?
4. Any other ideas?

Thanks for any help, my friend's friend will be very grateful for insights anyone may be able to provide.

 

[shadowstryker]

Is it a friend of a friend or you we're talking about? Maybe your friend's friend would be better suited to post here and could possibly provide more info.

A 30mg Oxy pill is a pretty decent amount for just one pill, are you sure it isn't extended release?

 

[Formidable]

if this "friend of a friend" was suffering from a failing liver or liver damage there would be noticeable physical symptoms, such as jaundice. furthermore, the bioavailability of oxycodone is much higher with oral consumption.

 

[Nofx5868]

Is it a friend of a friend or you we're talking about? Maybe your friend's friend would be better suited to post here and could possibly provide more info.

A 30mg Oxy pill is a pretty decent amount for just one pill, are you sure it isn't extended release?

I can answer any other questions anyone may have. It's also definitely not extended release, it's a 30mg IR roxy, and like I said, another friend uses them to great effect.

 

[Blackout2906]

It's either fake pills or tolerance issue ... I don't think there's any gray area with this subject matter. Check your source and make sure you're getting quality product.

 

[Formidable]

if this friend has no tolerance and they are doing the same amount as everyone else in the room but not getting the same results it would indicate a possible neurological issue. i know that's vague but this situation honestly doesn't make any sense.

 

[SKR]

^That's a pretty fair assessment really. If it were me I would need 10 of those pills for a 30min buzz and to hold me for 17hrs, but you should get high by simply swallowing one 30mg pill if no tolerance, should get a lil buzz with a low tolerance using my loose definitions of tolerance.

May be you just need more, I implore you to stop!

 

[Formidable]

after doing a bit of research on what could cause random opiate tolerance i came across a study done on the mc1r gene and its effect on the opioid receptors. but if you don't have red hair the chances are high that you don't carry this gene. however this isn't to say it's impossible.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1362956/

 

[Nofx5868]

Ok, I think I've figured out what is going on here! Maybe someone here who knows a bit more about the science behind this all can help me piece everything together, but I definitely think I'm onto something...

According to my research, there are two main enzymes that metabolize oxycodone - the primary enzyme is CYP3A4, and the secondary is CYP2D6. Oxycodone is metabolized by CYP3A4 into noroxycodone, an inactive substance, while the CYP2D6 metabolizes it into oxymorphone, the (good) active substance. The efficacy of each enzyme pathway varies greatly from person to person, and some people, referred to as "ultra-metabolizes", have enzymes that act upon the oxycodone so quickly that very little of the active ingredients are created (IE the CYP3A4 enzyme rapidly breaks the oxycodone down into an inactive substance, while CPY2D6 actually produces very little oxymorphone). My understanding from all this is that the more of the drug that is metabolized by your CYP2D6, the more potent the effects will be. This means that there are two ways to increase the effects - either prevent the CYP3A4 from metabolizing the substance, or increase the amount that is metabolized by CYP2D6.

My research has led to a couple other discoveries that seem to support my theory. If you refer to my first post, you'll see that I mentioned my friend noticed much stronger effects when the oxycodone was taken in the form of a cough syrup. This is (apparently) because the cough syrup also contains dextromethorphan (DXM), which is primarily metabolized by CYP3A4 - this means that more of the oxycodone will be metabolized by your CYP2D6, leading to more oxymorphone. Another fact that supports this theory, that I didn't specifically mention before, is that the previous experiences that yielded positive results were from oxycodone that also contained acetominophen... and guess what, that is also metabolized by CYP3A4, which again leads to more oxymorphone. These two facts seem to strongly support my theory, unless I'm missing something.

Based on everything I've found, it looks like my friend will need to supplement his oxycodone with something else that inhibits (occupies) the CYP3A4 enzymes, but does not inhibit the CYP2D6 enzymes. One item that meets this criteria is grapefruit juice, but there are a few others that I am currently looking into that may do the trick as well. I'll share this information with my friend and report back with his new findings. In the meantime, can anyone here add any insight here that may help improve my friend's experience, or correct anything that I may have gotten wrong? One question I have in particular is, how much grapefruit juice should be consumed, and when? I don't know enough yet to know if the juice should be taken immediately before each dose of oxycodone, or if it should be consumed regularly (a couple times a day) during any time period that my friend will be using oxycodone? Anyway, thanks in advance for any help...