what causes my slow metabolism of drugs?

[Altered Perception]

My body reacts the EXACT same way to certain drugs as a person with hepatic liver impairment would. I experience side effects and a hypersensitive reaction to medications far below the thearaputic dose. I experience a ridiciliously long onset time for certain medications to kick in. I experience an accumulative effect towards medication upon redosing many hours later.

In fact the reaction between myself and someone with liver disease is so identical I was convinced i had liver damage after recently i suddenly developed even more sensitivity to my regular dose of oxycodone ive been taking everyday for the last 5 years for chronic pain. While most people develop tolerance to opiates i suddenly went the opposite direction and had to cut my dose in half as thats all i can tolerate now.

After extensive liver tests using both ultrasound and blood tests, it all came back clear. So i had to re-evaluate the situation and looking back on my past history i found that ive been experiencing similar issues for many years. In fact 5 years ago i made a topic on bluelight asking why it was taking tramadol 5 hours to kick in. And then i had the same problem with an oral dose of meth which took up to a crazy 7 hours to start working and now im having the exact same problem with my ADHS medication Ritalin.

The first time i noticed these problems i had a cypd liver enzyme test to find out if my liver enzymes were the cause of all my sensitivity to tiny doses of medications, the increased side effects and the very slow onset times. I was certain my test results would come back abnormal because the association between my symptoms and the ones mentioned in liver enzyme problems fit like a glove and yet the test came back negative leaving me even more confused.

I was told to repeat my dose of Ritalin several times a day and yet with each repeated dose the reaction i have is doubled then trippled because i seem to have an extremely slow clearance time and lagging onset and bioavalibility. The same thing happens when i repeat my oxyxodone dose. Every dose i take within a day has to be less than the previous dose to compensate for the accumulation effect and delayed clearance time.

My bod react like someone with liver damage or impaired liver enzymes but tests have shown i have neither. So where does that leave me? Im open to theories. Thanks

 

[Altered Perception]

Also worth mentioning the problem is not due to a slow digestion and it usually takes me 15 min - 40 min to process all other non-psychoactive medications like betablockers. The problem only occurs with specific psychoactive drugs

 

[sekio]

Do you have trouble with gastric reflux or acidity? if your GI tract is too acidic it's possible that some drugs would be less well absorbed than they should

 

[Altered Perception]

As you know I have a medical condition known as Autonomic Dysfunction and just as the name suggests I bounce between the two opposite extremes with too much Acid reflux one day to not having enough acid the next day.

When you say less well absorbed does that mean the strength of the medication is also comprimized? Because I still seem to get the full effect but onset time is greatly increased and half-life is also effected.

Here is another clue if it helps with this puzzle; The medication with the longest onset time for me is Modafinil. If I posted how long it takes for it to start working I dont think you guys would believe me but here it goes: Around the 11 hour mark.

Also here is another clue; If I take tramadol together with my oxycodone I seem to be able to piggyback off the rapid onset time of the oxycodone. Otherwise without it the tramadol takes up to 5 hours to work. I know its a pro-drug that needs to be converted but it shouldnt take as long as it does.

Seiko, Thanks very much for replying to my post, i really appreciate it

 

[sekio]

This makes me think the problem is not with absorbtion but rather your mind responding to the presence of drugs in your body. Food gets eaten, digested, absorbed, and excreted again in a period of ~48 hours. Sugar, water, fat, etc for instance is absorbed in under an hour. It should not take upwards of 11 hours to absorb a dose of the fat-soluble drug modafinil. It's entirely possible that you are feeling the effects but not "noticing" them.

Do you always take drugs in the same dose/setting? Have you ever tried taking your oral medications through another route (e.g. plugging?) Have you had blood drawn to confirm medication is making it into your body?

 

[ebola?]

What happens when you use routes of administration other than oral?

ebola

 

[sekio]

More disorganised, rambling thoughts:

It is curious that "fun psychoactives" - opioids, stimulants and the like - are the drugs you have issue with.

How long have you been using stimulants and depressants, respectively? Do you try to achieve euphoria or other good feelings / a "high" with your usage? Have you ever, and if so, how long?

Do you use drugs in the same setting (location, time of day, emotional/mental state)?

How are you judging the effects? Do you have some objective measure to judge drug efficacy with (pupil diameter, blood pressure, EEG) or are you going by "feel"?

Experiment: Take a bolus dose of oral niacin (vitamin B6) and time how long it takes you to feel the flush from it. (Niacin causes blood vessels in the skin to dialate, making you feel warm and flushed for a few minutes. It's a pretty visible indicator compounds are making it into your blood.)

If your enzymes were messed up, it would not explain why only the "fun" psychoactives are effected. It would also likely result in either a prolonged effect profile (in the event the metabolic enzymes were not working) or generally reduced efficacy (in the case of too many enzymes) for most drugs, not a delayed onset and unreliable effects.

Too much or too little gastric acid changing the absorption rate of drugs seems unlikely. Acid levels would change the effectiveness of the drugs because some of it would remain in the intestine. It would also effect the absorption of other drugs too, so I doubt that theory now.

Anecdotally, I've heard many stories of modafinil experiences that basically are summed up as, "I've been awake, alert, and working for 36 hours since I took modafinil, but I don't feel it kicking in yet." - especially in recreational stimulant users.

I also know that in chronic recreational drug use, the body adapts to build tolerance to drugs based on the situations they are used in. For instance, a heroin user may find that it takes them a certain quantity of dope to get high when they're at home, but if they go somewhere new, or use in a different setting (different time of day, with different people, different ROA) it can seem more effective. So if you're using oxycodone habitually at around the same time every day, say before breakfast, you will eventually reach a time when it seems like it's not doing anything. You can get around this to an extent by switching it up or taking breaks.

 

[Foreigner]

If this is all reactions to oral based drugs, then it could be genetic. The CYP450 group of liver enzymes can have drastically different rates of metabolism, some slow, some normal, and some rapid.

 

[Altered Perception]

It's entirely possible that you are feeling the effects but not "noticing" them.
Do you always take drugs in the same dose/setting? Have you ever tried taking your oral medications through another route (e.g. plugging?) Have you had blood drawn to confirm medication is making it into your body?

What happens when you use routes of administration other than oral?
ebola

Perhaps you are right. The whole reason I discontinued the modafinil was because I wasn't feeling it at all in normal doses of 100mg. I am usually very sensitive to psychoactive substances so I thought It would be the same for modafinil but all it did was put me to sleep and give me vivid dreams. So then the doctor asked me to take it up to 200mg followed by 300mg until I get results and finally at 300mg it hit me hard but it happened 11 hours later.

I always take drugs in the exact same dose and settings at home. My method is ALWAYS oral route. Although that one time I tried meth (you may remember my posting about it) I got tired of waiting 7 hours for it to kick in so I snorted a line and it worked within 30 minutes, but then something very unexpected happened: the stuff that dripped behind my throat and into my stomach caused a secondary effect which hit me 7 hours later and that accumulation was just too much for my body to handle. I haven't snorted since.

If this is all reactions to oral based drugs, then it could be genetic. The CYP450 group of liver enzymes can have drastically different rates of metabolism, some slow, some normal, and some rapid.

I actually had a CYP450 liver enzyme test 5 years ago when i first posted about these issues on the forums here and someone suggested I take the test, it came back normal but I too thought exactly as you did because it seems like the logical reason. Perhaps the test was faulty ? Maybe I should repeat it?

Also I never used to have any of the listed issues prior to my drug overdose which caused my disability and damaged my Autonomic Nervous system 15 years ago. All of these problems started afterwards. I used to be a raver for 5 years and take drugs every weekend and each time my response to every drug I tried was just as normal as the rest of the population out there.

 

[ebola?]

The whole reason I discontinued the modafinil was because I wasn't feeling it at all in normal doses of 100mg.

I find modafinil really subtle if administered when well-rested.

ebola

 

[Altered Perception]

I thought I would reply to these questions in a separate column here if that's okay.

How long have you been using stimulants and depressants, respectively? Do you try to achieve euphoria or other good feelings / a "high" with your usage? Have you ever, and if so, how long?

Before developing Autonomic Dysfunction I used for 5 years almost every weekend and I did it to get as high as I could. Since the overdose and disability I am no longer able to achieve any euphoria because I am incapable of taking the high enough dose required for euphoria as that would most likely kill me in my current hypersensitive state. Even therapeutic doses are a challenge so i only take the minimal active dose for purely medical purposes.

Do you use drugs in the same setting (location, time of day, emotional/mental state)?

Yes to all of the above.

How are you judging the effects? Do you have some objective measure to judge drug efficacy with (pupil diameter, blood pressure, EEG) or are you going by "feel"?

I judge the effects by any slight change to my mental or physical state and by feel, for example when i get pain relief from oxycodone I know it has worked but when i overdo it by a fraction I get respiratory depression, bradycardia etc. But other substances like stimulants (which I am recently trying out for Chronic Fatigue and hypersomnia) tend to hit me harder than I prefer, even at very small doses and when i end up feeling ill its often reflected in my body temperature, blood pressure and heart rate and feeling like my eyes are about to pop out of my head.

Experiment: Take a bolus dose of oral niacin (vitamin B6) and time how long it takes you to feel the flush from it. (Niacin causes blood vessels in the skin to dialate, making you feel warm and flushed for a few minutes. It's a pretty visible indicator compounds are making it into your blood.).

Great advice from an obviously wise man. I will do that and report back.

So if you're using oxycodone habitually at around the same time every day, say before breakfast, you will eventually reach a time when it seems like it's not doing anything. You can get around this to an extent by switching it up or taking breaks.

That's exactly the point I had reached after 4 years of use... but then suddenly last week following some horrible recent adverse effects to MDVP (I bought it thinking it was meth) it just changed something in my body and I'm experiencing all these side effects to my regular everyday dose of oxycodone so Ive had to cut back even further. My initial reaction was that MDVP had damaged my liver but after tests thats not the case so I'm confused what's happening and so here I am trying to make sense of things. And I cant express how grateful I am that you guys are brainstorming on this.