Strange O-desmethyltramadol withdrawal

[belligerent drunk]

I originally thought about posting this in BDD, but I think the folk there will have no idea, so regardless of probably little discussion value, I'll post it here. It'll be a long post, but I'll try to provide a TL;DR at the end.

Preface: I've been using codeine daily for about half a year, skipping a day or two a few times each month. For about two months I've been using 500-650 mg taken in one dose, always on an empty stomach (>4 h since last meal), usually in the evening 10-15 minutes before dinner. During the day I don't really feel much discomfort, nothing to write home about anyway. When I skip a day or two, I start feeling slightly more discomfort as the 24 hours-since-last-dose mark approaches and it kind of stays on that level until about 70 hours, at which point I start feeling a little better. So, my tolerance and general level of dependence is fairly low. I've also never gone through hardcore opioid withdrawal, I guess that's worth mentioning as well. This is my first time using opioids daily long-term.

The problem: after reading about O-desmethyltramadol (O-DT) I decided to give it a try, so I ordered 2 grams. I assume it's a racemate, so it has NRI properties in addition to being an opioid. It arrived a few days before I had a short week, so I didn't need to wait long to give it a proper try. I consumed the 2 grams really fast (way faster than planned) as I had nothing to do at home. First few days I didn't take much to assess the way I react to it, but the last 3 days I took it two times during the day (around noon and then about 4pm), each time ca 250 mg. So that makes it 1.5 g in 3 days, total of 5 days for 2 g.

Strange things started almost instantly. On third day (when I hadn't used a lot yet) I felt pretty off in the morning, which was alleviated by taking the drug so it's safe to assume it was withdrawal. When I ran out, the next morning I woke up feeling pretty bad. The symptoms were identical to classical opioid withdrawal, only way more pronounced. By the 24-hour mark I was pretty much in fetal position on my bed feeling like death. As any genius would do, I figured that I'll try to "skip" the torture by getting drunk, so I started drinking, but it only seemded to make the matter worse yet I continued anyway. By about 9 pm I decided to try to sleep, but restless arm syndrome (yeah, arm not leg) wasn't letting me so I consumed 3 mg of bromazepam (I don't take benzos, so I have no tolerance), about 1 g of valerian extract and the last 40 mg of O-DT I had left for emergency, the situation resembling an emergency, honestly. I fell asleep quickly, I imagine, even though I don't really remember much after taking the other drugs.

What is even stranger, now, is that I woke up feeling fine. Fine as in exactly the way I would feel on the second day of abstinence from my usual codeine, perhaps ~10% more intense. Everything had returned to "normal". So what puzzles me is why the withdrawal was:
1) so intense
2) so short
3) started so soon

O-DT has a remarkable half-life of 8-10 hours and it has an active metabolite, so I would not imagine withdrawal starting practically 12 hours after last dose given my low tolerance/dependence. 3 days of semi-heavy use is not enough to cause a spike in tolerance/downregulation, is it?

Regarding the drinking, I did start pretty early. One study says that acetaldehyde does something with the opioidergic system, although I fail to completely understand what (would appreciate an explanation though!), but it seems like it may agonize it. Yet another study reports that acetaldehyde condenses with some endogenous opioid peptides making them inactive, so that should have an antagonistic effect.

This happened last week and I've been back to my codeine schedule as per usual. Right now I'm approaching the 48 hour mark since last dose and not feeling anything out of the ordinary. I ordered more of the O-DT, partially out of curiosity - I'm planning on doing some experimentation on myself with it. Yeah, I can be a masochist. Also, the vendor seems to be trustworthy, so I don't imagine I got something else or the drug was very impure (and I didn't notice any other effect of the drug that shouldn't have been there). I didn't run a test on it, because in all honesty I'm very lazy, but I might explore it with the second order.

TL;DR Practically no opioid dependence/withdrawal upon abstaining and no previous strong opioid withdrawal experiences. Took average-high doses of O-desmethyltramadol for 3 days, total of 1.5 g. Experienced very short (<20 hours) yet intense withdrawal that started as early as 12 hours since last dose. Possible explanation?

Thanks for your input in advance!

 

[Opiatehell85]

Hey BD,

do u think your withdrawal could of been from the codeine use and not the odt? I know you haven't had them previously but I'm kinda thinking that that's what has caused it? I know that when I move onto something else when I'm out of codeine eg morphine I still got some withdrawal and cravings for the codeine high, even when on the bupe I still had withdrawal from codeine especially on days 3,4,5. Just a thought.

you must have quite a high tolerance or you wouldn't be able to take 650mg at once, even for me after three years of codeine abuse I could never go higher 450/500mg without feeling breathless etc. I really do think you have a little addiction going on with the codeine, but I'm no expert obviously

hope ur feeling well today and not in discomfort my friend xoxo

 

[serotonin2A]

Codeine is a weak opiate, but using it everyday for 6 months could definitely put you on the edge of a dependence. Your desmethyltramadol binge probably worsened your dependence enough that you experienced withdrawal.

You stated that the symptoms were consistant with opioid withdrawal, but more pronounced. But have you ever experienced severe opioid withdrawal?

As people descend into opioid addiction, there are sometimes instances where withdrawal is unusually brief or mild. These are opportunities to escape an unpleasant fate, but are often not recognized as such until it is too late.

 

[clubcard]

It's a pure mu agonist so it won't replace a phenanthacine opiate (delta agonist) BUT it does raise serotonin levels so it does give an atypical withdrawal syndrome.

 

[serotonin2A]

It's a pure mu agonist so it won't replace a phenanthacine opiate (delta agonist) BUT it does raise serotonin levels so it does give an atypical withdrawal syndrome.

I don't believe that there is a delta component to the opiate withdrawal syndrome. The standard laboratory test to study whether opioids are likely addictive is to assess whether a compound can suppress the morphine withdrawal syndrome in rodents or monkeys. Pure mu agonists like fentanyl can completely suppress the morphine withdrawal syndrome, suggesting it is entirely due to mu effects.

 

[aced126]

I don't believe that there is a delta component to the opiate withdrawal syndrome. The standard laboratory test to study whether opioids are likely addictive is to assess whether a compound can suppress the morphine withdrawal syndrome in rodents or monkeys. Pure mu agonists like fentanyl can completely suppress the morphine withdrawal syndrome, suggesting it is entirely due to mu effects.

Surely opioids like buprenorphine (which is much less addictive than morphine) can suppress morphine withdrawal syndrome?

 

[clubcard]

I don't believe that there is a delta component to the opiate withdrawal syndrome. The standard laboratory test to study whether opioids are likely addictive is to assess whether a compound can suppress the morphine withdrawal syndrome in rodents or monkeys. Pure mu agonists like fentanyl can completely suppress the morphine withdrawal syndrome, suggesting it is entirely due to mu effects.

I can assure you that their is. If someone with a codeine (Pepsi) habit switches to tramadol, it stops the sniffles, but you get a full helping of the aches & pains along with the craving. I think I can even dig out a paper but from personal experience (after total hip replacement), tramadol is not you=r friend. I got swapped to ethoheptazine which is a partial agonist and I was STILL better.

 

[serotonin2A]

I can assure you that their is. If someone with a codeine (Pepsi) habit switches to tramadol, it stops the sniffles, but you get a full helping of the aches & pains along with the craving. I think I can even dig out a paper but from personal experience (after total hip replacement), tramadol is not you=r friend. I got swapped to ethoheptazine which is a partial agonist and I was STILL better.

The things you are bringing up don't have anything to do with delta. Tramadol is a prodrug to a moderate strength opioid. Thus, there is an upper ceiling to how much withdrawal it can suppress. Same with codeine...if someone is using a high dose of morphine (say for example several grams per day) then it is impossible to completely suppress the withdrawal syndrome with codeine.

Using tramadol as an example in this discussion is also extremely problematic because of its complex pharmacology. The upper dose you can use to suppress withdrawal is limited by its seizure-inducing capacity. Plus, higher doses induce seconday effects like stimulation that may actually worsen withdrawal in some people.

What is actually relevant to this discussion is whether fentanyl or another selective full mu agonist can suppress codeine withdrawal. The answer is that fentanyl can completely suppress codeine withdrawal.
.

Surely opioids like buprenorphine (which is much less addictive than morphine) can suppress morphine withdrawal syndrome?

Sure, but what does that have to do with delta receptors? Clubcard was claiming that opiate withdrawal has mu and delta components. If that is the case then a selective mu agonist would not be able to completely suppress opiate withdrawal.

Partial mu agonists may or may not be able to suppress withdrawal depending on the efficacy of the dependence-producing drug and the actual level of dependence. So buprenorphine may not be able to completely suppress fentanyl withdrawal if someone is using extrrmely high doses of fentanyl -- you might have to use a full agonist like methadone.

 

[clubcard]

If you have a HUGE amount or a very potent mu agonist, you won't notice the lack of delta. But look at the work of H Schmidhammer. Mu+delta makes stronger analgesic (eg codeine (prodrug to morphine) - check delta affinity compared to tramadol).

I DO have personal experience of this - YMMV true, but try getting a decent codeine habit & swap for the same amount of tramadol... and good luck.

 

[belligerent drunk]

Codeine is a weak opiate, but using it everyday for 6 months could definitely put you on the edge of a dependence. Your desmethyltramadol binge probably worsened your dependence enough that you experienced withdrawal.

You stated that the symptoms were consistant with opioid withdrawal, but more pronounced. But have you ever experienced severe opioid withdrawal?

As people descend into opioid addiction, there are sometimes instances where withdrawal is unusually brief or mild. These are opportunities to escape an unpleasant fate, but are often not recognized as such until it is too late.

No, as stated in the OP, I've never experienced severe opioid withdrawal, but from what I can understand the symptoms match.

I procured some more and did another binge of 400-600 mg/day for about 10 days. The withdrawal that followed was identical to the first. I'm back to "normal" now though. An interesting thing I noticed back then and now is that taking codeine AND O-DT produces an allergic reaction, an immense histamine release perhaps? The symptoms are: unbearable itchy sensation all over the body, moderate swelling of lips and some other parts of the face. I'm not prone to itchiness when taking either of the drugs alone, most of the time I don't even notice any. What could explain this kind of synergy?

 

[clubcard]

Tramadol doesn't cover a codeine habit - as I know from bitter experience. I was prescribe codeine and switched to tramadol, and suffered a withdrawal.

 

[serotonin2A]

Tramadol doesn't cover a codeine habit - as I know from bitter experience. I was prescribe codeine and switched to tramadol, and suffered a withdrawal.

Tramadol is a pretty weak opioid. It isn't suprising that you didn't get much relief. I've been prescribed both and codeine definitely has higher maximum efficacy; I'm sure it could support a stronger dependancy than tramadol. You are likely to experience withdrawal anytime you switch from a stronger to a weaker opioid with lower efficacy.

procured some more and did another binge of 400-600 mg/day for about 10 days. The withdrawal that followed was identical to the first. I'm back to "normal" now though. An interesting thing I noticed back then and now is that taking codeine AND O-DT produces an allergic reaction, an immense histamine release perhaps? The symptoms are: unbearable itchy sensation all over the body, moderate swelling of lips and some other parts of the face. I'm not prone to itchiness when taking either of the drugs alone, most of the time I don't even notice any. What could explain this kind of synergy?

All opioids can induce histamine release. Opiates are especially bad and codeine might be one of the worst ones because the dosages are so high. You are taking it for the 10% that is metabolized to morphine , but codeine itself can probably induce histamine release. You are lucky that you don't get really itchy with just codeine. Adding another opioid would make the histamine reaction much worse.

 

[belligerent drunk]

All opioids can induce histamine release. Opiates are especially bad and codeine might be one of the worst ones because the dosages are so high. You are taking it for the 10% that is metabolized to morphine , but codeine itself can probably induce histamine release. You are lucky that you don't get really itchy with just codeine. Adding another opioid would make the histamine reaction much worse.

Yeah, isn't the reason IV codeine is a really bad idea because of its histamine releasing property (which is too much given the needed dosage)? Anyway, the reason I'm puzzled is because the first time this allergic reaction occurred I had not taken O-DT for about 24 hours, so this definitely cannot be a case of just simple "addition" of effects, there is definitely some synergy. Why?

 

[clubcard]

From 100mg tramadol to 80mg DHC - delta withdrawal feels different, try it and see,

 

[serotonin2A]

From 100mg tramadol to 80mg DHC - delta withdrawal feels different, try it and see,

I'm not trying to say that the withdrawal syndromes don't feel different. They very well may feel different. My point is that it is a big jump to go from your observation to the conclusion that what you experienced is due to effects on the delta receptor.

There are at least three different receptors that opiates hit -- mu, delta, and kappa. Delta activation has never been shown to contribute to the morphine withdrawal syndrome. In contrast, kappa agonists produce a withdrawal syndrome. So why assume that the difference you detected is caused by delta, when it might actually be related to kappa, or it could simply be mu efficacy differences?

 

[clubcard]

Mu + Delta has been proven to multiply up potency - I've already pointed out the leader in this field, there are dozens of patents (so, no excuse, you can read them) and another dozen papers - which I bought purely for interest but they are in a secure format that uses a different Adobe reader so I cannot copy.... but the patents say it all. Don't assume affinity is full, partial, silent, inverse or an - tagonist in it's effects. I speak from experience & from doing my homework.

 

[serotonin2A]

Mu + Delta has been proven to multiply up potency - I've already pointed out the leader in this field, there are dozens of patents (so, no excuse, you can read them) and another dozen papers - which I bought purely for interest but they are in a secure format that uses a different Adobe reader so I cannot copy.... but the patents say it all. Don't assume affinity is full, partial, silent, inverse or an - tagonist in it's effects. I speak from experience & from doing my homework.

Take a look at this reference.

http://www.ncbi.nlm.nih.gov/pubmed/11602675

Chronic delta activation does not produce a withdrawal syndrome. There are certainly interactions between mu and delta receptors, but that doesn't necessarily mean that delta receptors contribute to the opiate withdrawal syndrome. Your view of the difference between tramadol and opiates is predicated on the belief that chronic activation of delta receptors causes a specific withdrawal syndrome that is distinct from the withdrawal syndrome produced by selective mu agonists. But I haven't seen any evidence supporting that interpretation.

 

[clubcard]

You went through all the patents as well?

 

[serotonin2A]

You went through all the patents as well?

It isn't my conclusion -- it is the current consensus of scientists who study opiate withdrawal. But I'm not really sure how the patent literature would be relevant in this case. Sure, there are lots of interesting opioids in the patent literature. But this is a discussion of biology and that puts its squarely in the realm of the peer reviewed literature.

 

[DarkStarCrashes]

I have been a daily tramadol user for years but have never ordered straight O-DT. I know that O-DT is a metabolite of tramadol however I was under the impression that pure O-DT had a lot more narcotic and traditional opiate qualities than taking tramadol does. I almost ordered some O-DT last week but my vendor stopped carrying it the day before I was ready to order. In the case of OP isn't say 400mg of O-DT drastically different in effects across the board than 400mg of tramadol?