First Bad Comedown
Bluelighter
- Joined
- Nov 26, 2010
- Messages
- 562
Grapefruit juice is well-known to interact with different drugs, especially stronger opiates like oxy.
Grapefruit juice is a potent inhibitor of the cytochrome P450 CYP3A4 enzyme.
Anything that inhibits the P450s can prolong or increase the effects of a drug.
And oxycodone is known to cause digestive problems like nausea and constipation with continued use!
But gastroparesis onset directly linked to grapefruit....twice.
Hmm.
That is rather severe, so I would assume that any inhibition of P450 enzymes could cause major metabolic changes in your system.
Hydrocodone is a substrate for both CYP3A4 and CYP2D6 enzymes, meaning they react to form a different compound (morphine).
But you are inhibiting the CYP3A4 with grapefruit, causing its effect to slow down.
Oxycodone is mainly metabolized by CYP2D6, so I don't know if there is any overlap.
Enzyme interactions are damned complex and understanding them won't really explain gastroparesis.
Maybe a little nausea and cramping, which is fairly common in some people.
But not hours of food sitting along with a lack of drug activity, then a sudden onset.
I should mention that a much milder version of those events has occurred to me with hydrocodone.
I find myself feeling almost nothing from it, until suddenly my gut starts moving.
It is the serotonin activity involved in digestion that exposes some of the brain pathways to the drug.
On nights when I am completely empty, there might not be ANY effect no matter how long I wait.
If I am too full, the effect is delayed until gastric movement occurs.
I literally have to time it just right to achieve the desired effect, and movement in my intestines is the key.
Its kinda like first and second-pass metabolism with alcohol.
A portion of it is absorbed in the mouth and stomach, but when the stomach empties into the small intestines, there is a sudden increase in blood alcohol content.
This is a big cause of alcohol poisoning, because people are not aware just how much they have had if their stomachs are full.
I have come to believe that there is much more than first and second pass.
I think that each section of the intestines represents its own metabolic potential, exposing more of the brain to the contents of the bloodstream.
Serotonin, which drives digestion, also influences blood distribution throughout the brain!
I imagine that this is a seamless event for most people, undetectable and uninteresting. The gut is firmly bound to the brain.
Only on night of heavy drinking could someone relate to the idea that the further down the gut it travels, the more regions of the brain will feel the effects.
Even all the way down to the large intestines!
In fact, the lower it goes the more euphoric the experience.
The seamless nature of the brain-gut circuitry has been interrupted in both of us.
Whatever the contents of our bloodstreams, be it alcohol or opiates, it does not effect our brains the same way.
Even smoking weed seems to rely on the movement down below!
Some days it feels normal, some days it does NOT.
I do not really believe that each segment of intestines further absorbs the drug...
Many drugs are easily absorbed in the first section of small intestine and stomach.
And the similar effect with smoking pretty much rules that out.
It is the smooth uniform contraction of the GI that allows the brain even, uninterrupted access to ANY drug or drug metabolite in the bloodstream.
I hope this is making sense to you.
Think of your gut like an accordian that is being constantly tugged on.
Sometimes it is not a gentle tug, but a pull or push.
The rhythm of this instrument is critical to the right notes being played in the mind.
It turns out that digestion, along with a number of emotions, are the result of a carefully tuned symphony of events.
And I never would have understood this so well before.
That is the best explanation I can offer you buddy.
Your accordian, your symphony, is out of sync.
In general, I recommend against regular drug use even opiates.
If I understand your other posts correctly, you often fail to feel any euphoric effects in the first place.
And you are tinkering with your metabolic enzymes...
If you didn't take oxycodone, you wouldn't have some of these problems.
But my guess would be that you DO feel some reward from taking it, or you just wouldn't be interested.
Combating gastroparesis with medication like D2 antagonists sounds like a very temporary solution to me - treating the symptom not the cause.
Medicine is capable doing more harm than good, especially when it come to anti-psychotics.
The cause is your damaged serotonin transmission.
And there is no drug to correct this, yet.
But I HIGHLY recommend exercise when you have a full stomach.
Healthy diet with lots of fiber and fluids should be a daily part of your life!
But if you stray from this healthy diet for even a day, I firmly believe that getting your BLOOD PUMPING will combat the lack of digestive ability.
It will push your symphony back into sync.
Anytime I have a bad feeling in my gut, especially when it effects my mood...I do pushups on the spot.
Especially if I really don't want to.
It is when I am the least comfortable that it makes the most difference.
I do quite a few - up to 300 in a night!
But it takes a lot to get me winded now.
The whole point is to do something that makes your heart pump faster.
This will increase enzyme activity, metabolism throughout the body, and encourage gastric emptying.
And it increases plasticity in the serotonin nerves in your brain!
Exercise is about the ONLY treatment that exists for MDMA related serotonin toxicity.
I wish I had more advice for you, but I don't.
Maybe a mild amphetamine like selegeline would help you.
Maybe low-dose ketamine.
I have considered both.
I will stick to my daily exercise regimen for now.
I really can't imagine what level of function I would be at without it.
You should be exercising every single day.
Good luck.
Grapefruit juice is a potent inhibitor of the cytochrome P450 CYP3A4 enzyme.
Anything that inhibits the P450s can prolong or increase the effects of a drug.
And oxycodone is known to cause digestive problems like nausea and constipation with continued use!
But gastroparesis onset directly linked to grapefruit....twice.
Hmm.
That is rather severe, so I would assume that any inhibition of P450 enzymes could cause major metabolic changes in your system.
Hydrocodone is a substrate for both CYP3A4 and CYP2D6 enzymes, meaning they react to form a different compound (morphine).
But you are inhibiting the CYP3A4 with grapefruit, causing its effect to slow down.
Oxycodone is mainly metabolized by CYP2D6, so I don't know if there is any overlap.
Enzyme interactions are damned complex and understanding them won't really explain gastroparesis.
Maybe a little nausea and cramping, which is fairly common in some people.
But not hours of food sitting along with a lack of drug activity, then a sudden onset.
I should mention that a much milder version of those events has occurred to me with hydrocodone.
I find myself feeling almost nothing from it, until suddenly my gut starts moving.
It is the serotonin activity involved in digestion that exposes some of the brain pathways to the drug.
On nights when I am completely empty, there might not be ANY effect no matter how long I wait.
If I am too full, the effect is delayed until gastric movement occurs.
I literally have to time it just right to achieve the desired effect, and movement in my intestines is the key.
Its kinda like first and second-pass metabolism with alcohol.
A portion of it is absorbed in the mouth and stomach, but when the stomach empties into the small intestines, there is a sudden increase in blood alcohol content.
This is a big cause of alcohol poisoning, because people are not aware just how much they have had if their stomachs are full.
I have come to believe that there is much more than first and second pass.
I think that each section of the intestines represents its own metabolic potential, exposing more of the brain to the contents of the bloodstream.
Serotonin, which drives digestion, also influences blood distribution throughout the brain!
I imagine that this is a seamless event for most people, undetectable and uninteresting. The gut is firmly bound to the brain.
Only on night of heavy drinking could someone relate to the idea that the further down the gut it travels, the more regions of the brain will feel the effects.
Even all the way down to the large intestines!
In fact, the lower it goes the more euphoric the experience.
The seamless nature of the brain-gut circuitry has been interrupted in both of us.
Whatever the contents of our bloodstreams, be it alcohol or opiates, it does not effect our brains the same way.
Even smoking weed seems to rely on the movement down below!
Some days it feels normal, some days it does NOT.
I do not really believe that each segment of intestines further absorbs the drug...
Many drugs are easily absorbed in the first section of small intestine and stomach.
And the similar effect with smoking pretty much rules that out.
It is the smooth uniform contraction of the GI that allows the brain even, uninterrupted access to ANY drug or drug metabolite in the bloodstream.
I hope this is making sense to you.
Think of your gut like an accordian that is being constantly tugged on.
Sometimes it is not a gentle tug, but a pull or push.
The rhythm of this instrument is critical to the right notes being played in the mind.
It turns out that digestion, along with a number of emotions, are the result of a carefully tuned symphony of events.
And I never would have understood this so well before.
That is the best explanation I can offer you buddy.
Your accordian, your symphony, is out of sync.
In general, I recommend against regular drug use even opiates.
If I understand your other posts correctly, you often fail to feel any euphoric effects in the first place.
And you are tinkering with your metabolic enzymes...
If you didn't take oxycodone, you wouldn't have some of these problems.
But my guess would be that you DO feel some reward from taking it, or you just wouldn't be interested.
Combating gastroparesis with medication like D2 antagonists sounds like a very temporary solution to me - treating the symptom not the cause.
Medicine is capable doing more harm than good, especially when it come to anti-psychotics.
The cause is your damaged serotonin transmission.
And there is no drug to correct this, yet.
But I HIGHLY recommend exercise when you have a full stomach.
Healthy diet with lots of fiber and fluids should be a daily part of your life!
But if you stray from this healthy diet for even a day, I firmly believe that getting your BLOOD PUMPING will combat the lack of digestive ability.
It will push your symphony back into sync.
Anytime I have a bad feeling in my gut, especially when it effects my mood...I do pushups on the spot.
Especially if I really don't want to.
It is when I am the least comfortable that it makes the most difference.
I do quite a few - up to 300 in a night!
But it takes a lot to get me winded now.
The whole point is to do something that makes your heart pump faster.
This will increase enzyme activity, metabolism throughout the body, and encourage gastric emptying.
And it increases plasticity in the serotonin nerves in your brain!
Exercise is about the ONLY treatment that exists for MDMA related serotonin toxicity.
I wish I had more advice for you, but I don't.
Maybe a mild amphetamine like selegeline would help you.
Maybe low-dose ketamine.
I have considered both.
I will stick to my daily exercise regimen for now.
I really can't imagine what level of function I would be at without it.
You should be exercising every single day.
Good luck.