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Mixing Tramadol and Methadone - What's the Real Deal Here?

SpunkySkunk347

Bluelighter
Joined
Jan 15, 2006
Messages
1,719
There is a TON of conflicting information regarding the alleged interaction between Tramadol and Methadone; it seems that every idiot wants to come on the Internet and chime in with their 2 cents.

Some sources say that tramadol displaces methadone at the receptor.

Some sources say that tramadol induces an enzyme which metabolizes methadone very rapidly, and diminishes effects.

Some sources say that mixing the two will provoke a lethal pharmacological interaction (as in, more lethal than mixing tramadol with any other opiate).

It is easy to imagine that these claims could have just been mere rumors that resulted when someone misinterpreted what someone else said. For example, someone might have read "Don't take tramadol if you're on methadone, because it blocks it" (meaning tramadol can't break through a methadone tolerance) as "Don't mix tramadol and methadone!!1 Tramadol blocks methadone!"

Then there are others who dismiss all these claims as the bullshit they most likely are. But who knows? The Internet is becoming an increasingly erroneous source of information (especially regarding drugs), and the Adv. Drug Disc. section of bluelight seems to be one of the last safe havens from these morons flocking to their computers.

Thanks for any response.
 
While certainly of use (in a general sense), this article doesn't materially elucidate the question at hand......

For the section devoted to tramadol, I must call bull-shittery on the very questionable usage of the 'at least 13' metric when referring to the cases of serotonin syndrome 'associated' from the [sum of] 'tramadol-alone' (i.e, acute) and 'other serotonergic drugs'. Even with the qualifier of sorts that follows this assertion, such assertions are very troubling, particularly when made by authors of such high stature. Inevitably, these numbers get quoted and referenced as virtual fact, which is simply not the case. Even a cursory search for documented cases of tramadol associated, related or suspected serotonin syndrome, hypertensive crisis etc will produce a far greater number. Furthermore, being that such events are largely a result of interaction, I would speculate that a good amount of actual cases are of an iatrogenic origin, and even if a case is ID'ed, such cases "tend" to not to find their way into the existing literature (something I have unfortunately witnessed, with little speculation). And of course, this does not take into account the many cases that were either misdiagnosed, clinically 'insignificant', and overlooked (even with toxicological reports). And there are the ME findings, which again, I have in a [confidential] # cases directly witnessed toxicological overlook of post-mort cause of death rulings, etc (wrongful 'what?', wink wink).

Point of my bitchfest, such vague numerical references actually find their way in med-school clin-pharm textbooks, hospital reference books, pharm/tox tables and...........coming soon, to a library near you (i.e, put into the wikipediphile's). What is not funny is the patient's that can suffer as a result of what may appear trivial overlook/misstep in context to the paper, or even journal as a whole......

This is not to detract from the legitimacy of the reference as a whole, or their authors (funny enough, I have personally communicated with one of the authors for his expertise in tox-pharm, and hold him in high-esteem), just a problem that is certainly not limited to this one article....

Oh......and as to methadone-tramadol, all I can really tell you (yes, after all that bitching), was that in my personal experience (meaning me personally, not as a clinician), years back when maintained on large doses of methadone, I ended up precipitating short-lived (but very real) opioid withdrawal by injecting two (or was it three) 100mg ampules of tramadol. As to po tramadol with methadone, I don't think I ever tried that......
 
still looking for feedback on this topic.
I've now read that mixing the two presents a risk of serotonin syndrome - is this true? I have never before heard that methadone was also a serotonin reuptake inhibitor, but apparently it is.
This worries me, as last Thursday at 9 am I took 40mg of methadone, and now tonight, being Saturday at 10pm, I've taken 300mg of tramadol. The methadone stopped giving me any noticeable effects sometime Friday, but I know the half-life is 24-36 hours, so that would mean there is still somewhere between 5 and 10mg of methadone still in my system. Should I be worried?
 
the only problem ( i guess you can say it's a problem) is combined NMDA antagonism. i have mixed tramadol with methadone before and had great results, but i also had klonopin, marijuana, and nicotine in my system
 
really? okay, thats reassuring to hear, was having an anxiety attack for a moment.
What doses were you taking if you don't mind me asking?

Think I should be worried at all about falling asleep?
 
200mgs tramadol, 30mgs methadone, and 1mg klonopin. methadone and tramadol both lower the seizure threshold too so that might be something to watch out for...
 
All at once I'm assuming?
I really regret taking that 300mg of tramadol tonight, its just making me feel anxious and sort of tense. I tried puking it up about an hour ago, but I dont know how well that worked, since I'm guessing most of it already absorbed into my system.
Oh well, I should start coming down in a few hours, then I'll feel comfortable with going to sleep.
And btw, I never knew tramadol was also an NMDA antagonist. I knew methadone was, but not tramadol. How potent of an NMDA antagonist is it?
I'm not too worried about seizures. I'm pretty below the "400mg daily limit" of tramadol, and I don't think 5-10mg of methadone lower my seizure threshold too significantly.
 
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Tramadol won do anything, you will just be wasting them if you decide to take them while your on methadone. The only thing you can do is stop taking methadone for a day or two then take something else and you will most likely feel it. Even after missing a day from dosing methadone i can feel the withdrawals pretty heavy and its not just all in my head. But yes give the done a break for a couple days and take something another opiate and you will most def. feel it, that or take benzo's while on the methadone and you will feel it that way too.
 
While certainly of use (in a general sense), this article doesn't materially elucidate the question at hand......

For the section devoted to tramadol, I must call bull-shittery on the very questionable usage of the 'at least 13' metric when referring to the cases of serotonin syndrome 'associated' from the [sum of] 'tramadol-alone' (i.e, acute) and 'other serotonergic drugs'. Even with the qualifier of sorts that follows this assertion, such assertions are very troubling, particularly when made by authors of such high stature. Inevitably, these numbers get quoted and referenced as virtual fact, which is simply not the case. Even a cursory search for documented cases of tramadol associated, related or suspected serotonin syndrome, hypertensive crisis etc will produce a far greater number. Furthermore, being that such events are largely a result of interaction, I would speculate that a good amount of actual cases are of an iatrogenic origin, and even if a case is ID'ed, such cases "tend" to not to find their way into the existing literature (something I have unfortunately witnessed, with little speculation). And of course, this does not take into account the many cases that were either misdiagnosed, clinically 'insignificant', and overlooked (even with toxicological reports). And there are the ME findings, which again, I have in a [confidential] # cases directly witnessed toxicological overlook of post-mort cause of death rulings, etc (wrongful 'what?', wink wink).

Point of my bitchfest, such vague numerical references actually find their way in med-school clin-pharm textbooks, hospital reference books, pharm/tox tables and...........coming soon, to a library near you (i.e, put into the wikipediphile's). What is not funny is the patient's that can suffer as a result of what may appear trivial overlook/misstep in context to the paper, or even journal as a whole......

This is not to detract from the legitimacy of the reference as a whole, or their authors (funny enough, I have personally communicated with one of the authors for his expertise in tox-pharm, and hold him in high-esteem), just a problem that is certainly not limited to this one article....

Oh......and as to methadone-tramadol, all I can really tell you (yes, after all that bitching), was that in my personal experience (meaning me personally, not as a clinician), years back when maintained on large doses of methadone, I ended up precipitating short-lived (but very real) opioid withdrawal by injecting two (or was it three) 100mg ampules of tramadol. As to po tramadol with methadone, I don't think I ever tried that......

Thanks to the person reviving this thread be because in consequence I got to get a glimpse of myself from nearly a decade ago.
 
GABA-A agonists are drugs like muscimol. Most popular sedatives act to increase the ability of GABA to activate GABA-A receptors, or make the activation last longer - e.g. benzos, barbiturates, alcohol.
On the flipside, the GABA-A antagonists have the opposite effect, they act as anxiogenic stimulants that cause seizures at higher doses. These are drugs like pentylenetetrazol and bicuculline. Usually these only find use in the testing of anti-seizure medications, that is, to reliably induce seizures of known intensity in animal models.

Typical blood concentrations of tramadol at a 400mg dose approximates out to around 3 uM (Peak plasma concentrations following chronic 400mg/day dose were approximately 0.6mg/L.[ref], m.w. tramadol = 263), and GABA-A inhibition is only relevant at around 100 uM. So it might be a reason for the increased seizure potential at higher doses, but I suspect it's less relevant than tramadol's many other targets it does bind.
 
Typical blood concentrations of tramadol at a 400mg dose approximates out to around 3 uM (Peak plasma concentrations following chronic 400mg/day dose were approximately 0.6mg/L.[ref], m.w. tramadol = 263), and GABA-A inhibition is only relevant at around 100 uM. So it might be a reason for the increased seizure potential at higher doses, but I suspect it's less relevant than tramadol's many other targets it does bind.
So not really relevant in the complex pharmacology of Tramadol. If I interpret it correct.

The mother of my kids is on 200/ 300mg a day. I assumed it did the opposit of benzodiazepines, antagonize GABA-a, but I have to retract that I guess.
 
GABA-A agonists are drugs like muscimol. Most popular sedatives act to increase the ability of GABA to activate GABA-A receptors, or make the activation last longer - e.g. benzos, barbiturates, alcohol.
On the flipside, the GABA-A antagonists have the opposite effect, they act as anxiogenic stimulants that cause seizures at higher doses. These are drugs like pentylenetetrazol and bicuculline. Usually these only find use in the testing of anti-seizure medications, that is, to reliably induce seizures of known intensity in animal models.

Typical blood concentrations of tramadol at a 400mg dose approximates out to around 3 uM (Peak plasma concentrations following chronic 400mg/day dose were approximately 0.6mg/L.[ref], m.w. tramadol = 263), and GABA-A inhibition is only relevant at around 100 uM. So it might be a reason for the increased seizure potential at higher doses, but I suspect it's less relevant than tramadol's many other targets it does bind.

Tramadol also binds to delta-opioid receptors, which can cause convulsions due to a downstream anti-gabaergic effect: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4382405/
 
200mgs tramadol, 30mgs methadone, and 1mg klonopin. methadone and tramadol both lower the seizure threshold too so that might be something to watch out for...

Yes, but clonazepam is a great anti-convulsant benzo, so ...
 
It's much the same as how THC causes indirect anticholinergic-like effects without actually binding to acetylcholine receptors.
The dry mouth? Actually a downstream anti-cholinergic effect or am going to fast in my conclusion's.
 
The dry mouth? Actually a downstream anti-cholinergic effect or am going to fast in my conclusion's.

And it also dilates your bronchi, increases heart rate and impairs memory like atropine and scopolamine. The withdrawal symptoms of long term heavy cannabis use resemble cholinergic toxicity, with symptoms like excessive salivation.
 
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