CYP2D6 production rate, DXM redose, DXO.

[Mracid]

Any1 know the production rate of CYP2D6 for an average male?

Now lets ask the question from another angle to get more answers,

Any1 know if when you redose low amounts of DXM over 12 hours you increase the ratio DXO/DXM in the blood compared to taking the whole dose one shot?

And does the body see the use of an enzyme as a message to produce more?

Thanks for reading and possibly answering .

 

[thadocta13]

Gosh I wish I was more proficient in pharmacokinetics. I know the basics and I know quite a bit from perusing BL for many years. But I wouldn't have the knowledge that an actual student of pharmacology or biochemistry would have. I have alot of experience with DXM though and I played around alot wth CYP2D6 inhibition via white grapefruit juice/grapefruits.

Now as for your question. Idk you knowledge of DXM but it is metabolized hepatically via CYP2D6 and like many drugs it affects its own metabolism by inhibiting that enzyme. As a result, redosing DXM at any point would cause a rise of DXO in the bloodstream because of the inhibition of the enzyme from the first dose. Taking a dose on a full stomach can cause this effect also. My theory on this based on experience is that the food causes a (obviously) delayed absorption rate of the drug. As the drug starts to enter the bloodstream in a small amount it starts to slowly inhibit the CYP2D6 enzyme. As the dose is slowly being absorbed and metabolized, the DXO/DXM ratio is increasing. I took a large dose 2 hours after dinner once and the dose slowly kicked in over a 2 hour period and was a very DXO heavy experience.

So the answer is yes there is a difference. A HUGE difference. Taking one single large dose will be absorbed relatively quickly and metabolized and it will reach the brain in a sufficient amount to do its thing. When staggering doses throughout a time period, the metabolism is affected and yes it causes a great deal of increase in DXO: DXM. Be careful doing this because this is how you will end up tickling your Sigma receptor and believe me you do NOT want to reach plateau Sigma. It is highly unpleasant and is practically exactly the same as having psychosis and schizophrenia. It is very difficult to remain rational and able to differentiate reality from delusion. It can be scarier than anything you've ever experience. It is a cold and scary experience unlike that of a difficult trip on a classic psychedelic.

Now as for more detail about the production rate/process of the CYP2D6 enzyme I'm not familiar with how it functions and how it is inhibited and how it becomes uninhibited after ceasing administration of an inhibitor.

 

[Mracid]

Thanks for the answer! Helps alot, I am not really trying to reach plateau sigma but rather wanted to know if I could lenghten a 1rs or 2nd plateau, as those plateau are more defined by DXO than DXM. Last night I divided a 350mg in 3 doses 3 hours apart making an increasingly intense trip that lasted about 10-12 hours and where I was moderately high, nowhere close to plateau sigma.

 

[adder]

DXM is metabolized by CYP2D6, so if anything, redosing actually causes the DXO/DXM ratio to drop and not increase in comparison to taking the same overall dose in one go. Also, why do you think 1st and 2nd plateau's are more defined by DXO and not DXM? DXM itself is a weak NMDA antagonist compared to DXO, why would you assume the effects of weakly dissociating doses are due to the latter and not the former? It appears that the truth is actually quite the opposite compared to the conclusions you arrived at. 1st/2nd plateau's effects are more due to DXM and redosing DXM makes less DXM be metabolized into DXO.

Anyway, I would venture a guess that redosing DXM over 12 hours could actually be dangerous.

 

[Mracid]

Well as the dosage increase the enzymes become saturated and a bigger amount of DXM should be accumulating so I thought the 3rd plateau was when you pass a certain level of enzyme saturation that would raducally increase the ratio of DXM/DXO, That was my thought.

And my thought about redosing is that yes it inhibits the enzyme but only the enzyme that metabolize it so technically, taking say 50mg instant or over 3 hours would give the same ratio of DXM/DXO if you split the dose equally. But Also with time the body can start reactivating some inhibited enzymes or make more, depends on how it actually works. Hence taking a medium dose over time would result in a low experiment that last longer.

Also about the plateaus, the 1rs and 2nd are dissociative, your perception is dissociated and your actions are but your mind is not really, but as you reach higher plateaus with DXM you get a serotoninergic effect that overloads the mind and dissociate your thoughts and make you lose the flow of your thoughts dissociating your mind. So I guess what I am saying is that I believe that NMDA antagonist action are not responsible for the dissociative side of DXM but for the perceptual alteration and intellectual complexity reduction. And that its the SSRI effect that overloads the mind to a point where it gets lost.

 

[adder]

I'm not a pharmacologist, so I just convey what I think based on my limited knowledge, but IMO as the enzymes get inhibited, less DXM is metabolized into DXO, still, it is not a complete inhibition, so I don't think we're talking about any real DXM accumulation unless one does indeed redose regularly for prolonged time. As you increase the dose of DXM, you also increase the levels of DXO, only not proportionally, so basically at all plateau's both DXM and DXO effects are present. The higher the dose, the more dissociation because NMDA antagonism gets more and more significant, this is not due to serotonergic effects of DXM (which obviously do play a great role in subjective effects). I suppose it is now pretty much agreed that high-dose dissociation and eventually anaesthesia are caused by dextrorphan. Other dissociatives with dissociative effects similar to DXM are poor serotonergics at best with some isolated exceptions. The pharmacology of DXM is certainly complex, but this one thing is certain as DXM itself has very low affinity at NMDA receptors.

 

[thadocta13]

Wow my bad I don't see how I mixed that up. That doesn't make sense what I said. A normal dose of DXM is rapidly converted into DXO where it exhibits NMDA and sigma effects and I think possibly pcp receptor effects. Grapefruit juice inhibits this enzyme and causes an increase in DXM levels. DXM produces effects different than DXO. I personally think that prolonged dosing of DXM causes a really high level of DXM and exhibits strong Sigma receptor effects. It is a very strange and intense experience similar to psychosis. This only occurs when taking multiple doses over a time period. Taking 2 doses of DXM I'm pretty sure both are readily metabolized into DXO. Also about 5 or 7% of the Caucasian population lack or are deficient in the CYP2D6 enzyme. There are alot of factors that play into the metabolism of DXM. It varies drastically person to person. I've seen it produce so many different effects in different people. Because of the differences in body chemistry and metabolism. Some people don't like it because it gives them a long weird buzz. Usually people deficient in CYP2D6. Some people rapidly metabolize it. And also sometimes I get different experiences on different doses because sometimes it feels like it is rapidly converted to DXO and produces a strong dissociative effect and other times it slowly kicks in but is a nice smooth strong buzz that feels more of a controllable dissociative effect. Feels like a little bit higher levels of DXM than DXO. This drug is just so of and unique in its broad range of effects. I would love to know more about how Plateau Sigma is achieved. If these drugs already bind to Sigma receptors then what happens to those receptors when DXM starts to saturate the receptors? Plateau sigma is very unique and occurs out of nowhere. All of a sudden your vision alters and.your body feels strange almost nonexistent and your thoughts become delusional and for me I get very paranoid. I have to calm myself down constantly. So why does this happen? It only happens when you keep taking doses and DXM builds up and IME it occurs after you have been under the influence for quite some time. Its like time plays a role. I cam fry all day on DXM but if I prolong it into the next day I almost always end up in plateau sigma. Usually it happens some time after my.last dose. As if it takes some time for the receptor to saturate or something. Anybody know more about this? Its so intriguing to me how this plateau is so unique and fucked up.

 

[Mracid]

Well I was curious, and I found a computer simulation of DXM double dosing and redosing, and it seems that when you double dose you do not increase the ratio of DXM/DXO altho when you redose more than 5-6 times you increase it and the more you redose the more its increasing (so by redosing 3 times there is not real change in the ratio as the liver isnt overloaded yet). Altho I was wrong with the plateaus and the ratio, the plateaus are created by the binding site affinity of the drug and metabolites. Also I think the SSRI action does amplify dissociation at higher dosage which contributes to the effect, and some link has been made between 5-HT1A activation through NMDA antagonists, so a SSRI increase serotonin levels which increase 5-HT1A receptor activation which (I assume here that there is a heteromere of 5-HT1A-NMDA) would lead to a greater decrease in NMDA activity.

 

[thadocta13]

Yes I would recommend to the OP to read William Whites DXM FAQ. It has graphs showing a normal dose, a dose with someone deficient in CYP2D6, one showing double doses, and one showing repeated dosing. You ate correct a 2nd dose does not raise DXM levels. The slope of the metabolism is slightly slowed. By its very similar to the graph line showing the first dose. DXM increases with repeated dosing and that's what causes Plateau Sigma. Very interesting that DXM has to build before it causes such a drastic change in effect. It definitely isn't NMDA action as DXO acts heavily on NMDA. And I feel like the Serotonin increase doesn't really contribute to its dissociative effects. Whenever I feel an increase in 5-HT it produces alot of side effects and has antidepressant properties. The reason I think this is because I will he frying very hard and I later in the trip I can feel the serotonin working. Affecting muscles, reflexes, my jaw chatters sometimes which is a unique effect of serotonin for me personally. The serotonin seems.to increase over time. It definitely adds to.the experience but I don't quite think it plays a major role in its dissociative effect. I feel like the obviously NMDAR plays a role and also Sigma and PCP receptor sites. Those two receptors are fascinating as they are responsible for a whole whore house of effects. I've done.alot of dissociatives and none come close to replicating the Plateau Sigma experience.

 

[thadocta13]

So to put it simply, repeated dosing over 12 hours will cause DXM levels to rise. Redosing does not. If you want a heavy DXO trip than taking a single large dose will do you just fine. Sometimes I redose with about half my original dose at about 1 1/2 hr after first effects to achieve a stronger dissociation and longer duration.

 

[Mracid]

That is what I was shooting for originally, longer duration, higher dissociation, and higher NET inhibition, as DXO retains NET inhibition. I simply decided to make things interesting by sliding in some generalized information about DXM to see if some1 would challenge it so that I can get new insights about how to see DXM pharmacologically speaking, but when I started the post all I wanted to know was if I redosed, I would change the Identity of the experiance instead of lenghtening it.

That post made me learn a shitload about DXM, cuz I learned by having theories challenged, new information sought for, and outside Ideas on how it works. So thanks for answers and have a good day!