Opioids Tramadol & Neurotoxicity

[DeathIndustrial88]

What are your thoughts on tramadol & neurotoxicity?

I've always wondered, since not only is tramadol a weak SNRI-type drug, but it also releases serotonin.
Drugs that release neurotransmitters have the potential to be neurotoxic.

This abstract says it has the potential to be & can cause things like Parkinson's Disease.
Can some one who's a little more knowledgeable read it & break it down a little in laymens terms?
Other than the SNRI effect, what would make tramadol neurotoxic?

Should some one like me who used 400mg doses daily every month (with 1-2 week breaks in between) for 10 years & went through tramadol withdrawal every single one of those months) be concerned with possible long term consequences?

What should some one who has experienced "Extensive tramadol intake alters redox balance through elevating lipid peroxidation and free radical leading to neurotoxicity and produces neurobehavioral deficits." monthly for years look out for?

I have had myoclonic jerks for the past 6-7 years with an unknown origin. They come & go in varying degrees every so often. Although they started after I accidentally gave myself convulsions & serotonin syndrome from mixing dextromethorphan & effexor, so it could very well be completely unrelated to my long term tramadol use.

I've also been a user of meth & amphetamines after different points in my life. So I can't really pinpoint any of my issues to tramadol.


Regardless of all that,
I'm curious if anyone has had any neuro-issues after using tramadol for a years & people's thoughts on what all this pathway signalling and it's different mechanisms have on the body, brain & how it can make a tramadol experience unique compared to other opioids.
Tramadol use to have an amazing high when I was opioid naive. Some times it matched the intensity of heroin for me, but with a more stimulated feeling.

I have tried effexor to see if it felt similar, but they really don't. And I find it hard to believe that some of the qualities tramadol has are either strictly it's opioid metabolite (which it may be) or just some weak silly SNRI effect. This drug seems to hit a lot more places than just those systems.

Neurobehavioral Consequences Associated with Long Term Tramadol Utilization and Pathological Mechanisms - PubMed

Tramadol is a synthetic analog of codeine used to treat pain of moderate to severe intensity and is reported to have neurotoxic potential. At therapeutic dose, tramadol does not cause major side effects in comparison to other opioid analgesics, and is useful for the management of neurological...

pubmed.ncbi.nlm.nih.gov

I also find this very interesting, as I use to binge drink coffee whenever I would dose tramadol. I felt like it potentiated it a great deal. And some how I never managed to have a seizure from it.

Caffeine attenuates seizure and brain mitochondrial disruption induced by Tramadol: the role of adenosinergic pathway - PubMed

Tramadol (TR) is an analgesic drug used to treat moderate-to-severe pain but it induces seizure even at therapeutic doses. The exact mechanism of TR-inducing seizure is not clear but inhibition of the serotonin, GABA, and nitrous oxide (NOS) pathways are the commonly proposed mechanisms...

pubmed.ncbi.nlm.nih.gov

 

[simstim]

If you've done the damage there's not a whole to do about undoing it and frankly worrying about it is more likely to cause symptoms than alleviate your worries.

Tramadol gives me a very pronounced tic. More gives me a seizure.

I think it's garbage and it's a dirty trick to call it an opioid.

My advice is to switch to kratom. It's a much better opioid once you find your dose sweet spot.

 

[DeathIndustrial88]

If you've done the damage there's not a whole to do about undoing it and frankly worrying about it is more likely to cause symptoms than alleviate your worries.

Tramadol gives me a very pronounced tic. More gives me a seizure.

I think it's garbage and it's a dirty trick to call it an opioid.

My advice is to switch to kratom. It's a much better opioid once you find your dose sweet spot.

See, now it's strange for me to hear that from people (well not really because tramadol is very fucking weak to me now a days).

but back in the day, about 1.5hr into the tramadol experience, it felt exactly like heroin, except more stimulating.

I don't know if I was a good metabolizer or what. But for me, tramadol beats the hell out of kratom any day.

I actually took 2 kratom 50mg extract pills yesterday and felt nothing from it. This is about the 100th (exaggerating a little) time I've tried kratom to no avail. I cannot say I've felt any sort of buzz or contentedness on kratom... like ever.
The confusion you have toward tramadol, I have with kratom. I can't understand why anyone would think kratom has any decent opioid activity whatsoever.


I also drank a shit ton of dirty poppy tea, which felt strong, strong enough to give me nausea and sedation, but there was absolutely no euphoria.
This seems to be typical of all my poppy seed experiences too.

Usually if an opioid works for me and makes me feel good, I'll get up and start doing things I wouldn't normally do (like cleaning, going for a walk, going out in public). I don't get any of this from kratom, poppy seed tea or my buprenorphine.

 

[WellTramer]

I use tramadol for 10 years and it is still good as an antidepressant and it is good for my chronic pain but i have to mix it with ibuprofen, metamizole or mušle relaxers or alprazolam.

 

[emkee_reinvented]

See, now it's strange for me to hear that from people (well not really because tramadol is very fucking weak to me now a days).

but back in the day, about 1.5hr into the tramadol experience, it felt exactly like heroin, except more stimulating.

I don't know if I was a good metabolizer or what. But for me, tramadol beats the hell out of kratom any day.

I actually took 2 kratom 50mg extract pills yesterday and felt nothing from it. This is about the 100th (exaggerating a little) time I've tried kratom to no avail. I cannot say I've felt any sort of buzz or contentedness on kratom... like ever.
The confusion you have toward tramadol, I have with kratom. I can't understand why anyone would think kratom has any decent opioid activity whatsoever.


I also drank a shit ton of dirty poppy tea, which felt strong, strong enough to give me nausea and sedation, but there was absolutely no euphoria.
This seems to be typical of all my poppy seed experiences too.

Usually if an opioid works for me and makes me feel good, I'll get up and start doing things I wouldn't normally do (like cleaning, going for a walk, going out in public). I don't get any of this from kratom, poppy seed tea or my buprenorphine.

Disagreed , imo Kratom till now beats the cake.


better then Oxycodone, better then o-DSMT. Codeine is nice though.

 

[simstim]

See, now it's strange for me to hear that from people (well not really because tramadol is very fucking weak to me now a days).

but back in the day, about 1.5hr into the tramadol experience, it felt exactly like heroin, except more stimulating.

I don't know if I was a good metabolizer or what. But for me, tramadol beats the hell out of kratom any day.

I actually took 2 kratom 50mg extract pills yesterday and felt nothing from it. This is about the 100th (exaggerating a little) time I've tried kratom to no avail. I cannot say I've felt any sort of buzz or contentedness on kratom... like ever.
The confusion you have toward tramadol, I have with kratom. I can't understand why anyone would think kratom has any decent opioid activity whatsoever.


I also drank a shit ton of dirty poppy tea, which felt strong, strong enough to give me nausea and sedation, but there was absolutely no euphoria.
This seems to be typical of all my poppy seed experiences too.

Usually if an opioid works for me and makes me feel good, I'll get up and start doing things I wouldn't normally do (like cleaning, going for a walk, going out in public). I don't get any of this from kratom, poppy seed tea or my buprenorphine.

Yeah you're never gonna feel kratom if you're on buprenorphine.

 

[DeathIndustrial88]

Yeah you're never gonna feel kratom if you're on buprenorphine.

I never felt kratom even before I knew what buprenorphine was & had short periods of abstinence even (where i tried it, kratom I mean). lol

I should reiterate that some kratom I do feel, even on buprenorphiine. But obviously the effects are not opioid effects, more akin to a good cup of coffee. Some times this can help me feel a little better. Although it's extremely mild, almost imperceptible & unpredictable. I think the 30+ other alkaloids are responsible for that. I wouldn't even classify kratom as a mu agonist if I had to go strictly by subjective effects alone


Taking heroin in the past completely elimated any desire or cravings for any other drugs in me. From alcohol, to meth, to benzos.. I Imagine this is why I never overdosed in all those years. The only drug I did still use and desire for a bit was cannabis. Probably because I was a stoner long before I was an opioid user & they compliment each other well.
Last night I tried kratom again to see if it'd even help with a mood lift, but still felt like going out & doing meth just to lift my mood & give me some energy (although I prefer opioids obviously) but the world is so fucked up right now that you can literaly find methamphetamine 100x easier than you can find opiates At least in my area. Pretty sad.

 

[DeathIndustrial88]

This say 7-hydroxymitragynine is a full agonist at mu.

"7-Hydroxymitragynine was found to be a full agonist at MOP and a competitive antagonist at DOP and KOP, while mitragynine and speciociliatine were partial agonists at MOP"

Investigation of the Adrenergic and Opioid Binding Affinities, Metabolic Stability, Plasma Protein Binding Properties, and Functional Effects of Selected Indole-Based Kratom Alkaloids

Selected indole-based kratom alkaloids were evaluated for their opioid and adrenergic receptor binding and functional effects, in vivo antinociceptive effects, plasma protein binding, and metabolic stability. Mitragynine, the major alkaloid in Mitragyna ...

www.ncbi.nlm.nih.gov

Does this mean kratom (or it's metabolite anyway) is a FULL agonist?
Shouldn't this mean a full agonist "high" should be able to be achieved with kratom?
I thought kratom was merely a partial agonist as far as opioid activity goes?


Has anyone felt a better effect from kratom than say buprenorphine? I always found buprenorphine to be much stronger than kratom by a long shot, even in opioid activity aspects. But if kratom produces full agonist effects, then i'm confused.

 

[simstim]

This say 7-hydroxymitragynine is a full agonist at mu.

"7-Hydroxymitragynine was found to be a full agonist at MOP and a competitive antagonist at DOP and KOP, while mitragynine and speciociliatine were partial agonists at MOP"

Investigation of the Adrenergic and Opioid Binding Affinities, Metabolic Stability, Plasma Protein Binding Properties, and Functional Effects of Selected Indole-Based Kratom Alkaloids

Selected indole-based kratom alkaloids were evaluated for their opioid and adrenergic receptor binding and functional effects, in vivo antinociceptive effects, plasma protein binding, and metabolic stability. Mitragynine, the major alkaloid in Mitragyna ...

www.ncbi.nlm.nih.gov

Does this mean kratom (or it's metabolite anyway) is a FULL agonist?
Shouldn't this mean a full agonist "high" should be able to be achieved with kratom?
I thought kratom was merely a partial agonist as far as opioid activity goes?


Has anyone felt a better effect from kratom than say buprenorphine? I always found buprenorphine to be much stronger than kratom by a long shot, even if opioid activity aspects. But if kratom produces full agonist effects, then i'm confused.

You aren't confused. Buprenorphine is far more potent than kratom

 

[DeathIndustrial88]

You aren't confused. Buprenorphine is far more potent than kratom

True.
Potency doesn't always equal better effects though right?
Bupe may be potent but it hardly activates the receptor compared to full agonists.
I guess I'm confused why some sites say 7HOM is a full agonist & others say partial.
And if it were a full agonist, shouldn't better effects be achievable if dosed high enough compared to a partial agonist? Especially isolated 7HOM?

 

[moonyham]

Yo bro I'm the same, first few weeks I tried tramadol it was like heroin for me too. But only if I took 200-300mg instead of 100.

If anything it was better than heroin. I was in a total state of bliss, nodding away as the world zoomed by in a blur.

 

[DeathIndustrial88]

Yo bro I'm the same, first few weeks I tried tramadol it was like heroin for me too. But only if I took 200-300mg instead of 100.

If anything it was better than heroin. I was in a total state of bliss, nodding away as the world zoomed by in a blur.

Same! Every time I'd get the script, I usually had to start out with 300-400mg spread out over an hour or so. Otherwise I wouldn't feel much. Even with no tolerance.
And this same dosage usually did it for me daily even after that. Of course the nods would get weaker & weaker but I actually kind of liked just feeling good & normal on tramadol.

Buprenorphine just makes me tired. And not in a good or euphoric way either.
I was much more content & productive on tramadol. It's too bad I can't use it instead of buprenorphine for maintenance.
Been having extensive cravings for it lately... like to the point where I wonder if it's even worth living the next 30 years of my life if I'm never going to get to be productive and enjoy feeling how I use to be able to feel. Sounds pathetic, but it's honestly where I'm at. Feeling more irritable & angry every day.
I thought tramadol was slightly more enjoyable in some aspects than heroin too, but once I started really getting into heroin, tramadol could barely hold me.

 

[crzydiamond]

It’s intriguing, how people have different experiences with these drugs.

Personally, buprenorphine gives me opiate energy ( as someone mentioned above, the “feeling good” where I get productive— clean the house, go outside n work in yard, etc. [not the meth type frenetic energy; I feel like anyone who’s done opiates-esp heroin when it was heroin and not fentadope— understands what I mean by opiate energy)

Mind you, I don’t dose bupe high. I take doses of about 1 mg 2-4 times a day. I try n stay at 2 mg but spacing it out even if I take 4 I feel good. But I also don’t really let it sit 15 min like they recommend. After about 5 minutes I invariably take a drink of water.

I think maybe that’s why I get full agonist effects. Even to the point of pinned eyes. I think if I’m lucky about half of the bupe actually gets in my system

Tramadol by itself could put me in a sort of “ relax on the couch in a floaty type way”. But I never had anything comparable to a dope high on it.

But I will say this for tramadol. It has excellent synergy with other opiates. ( i dont know about bupe as I didn’t have both simultaneously)

But back when I had easy access to tramadol and oxy (real) and fentanyl patches (Sandoz sticker type that I abused the heck out of orally. A piece of that in my gum was amazing. Side note: Weirdly, no other sticker type brand produced that effect and I really believe that was why they went out of production for a time back in 2012-13. ) I felt better; better high if I took a tramadol or 2 when I was using the patches or 15 mg Oxys.

Tramadol potentiates opiates IME

And there must be something to that because last year every time I used I came up positive for heroin, fentanyl, and *tramadol*. ( SE Pennsylvania )

I never took any tramadol during that time so it clearly was mixed in the “dope”

Does anyone else notice the synergy between tramadol and opiates ?

 

[DeathIndustrial88]

You might be a poor metabolizer of tramadol, crzydiamond.

Before I got into heroin & then ontop bupe, tramadol use to produce almost identical "highs" to me as heroin. Especially around 1.5hrs into a dose.
I'd be scratching my body & my nose would turn red (from rubbing it so much). I was literally in heaven. I could nod, but if I needed to do something, I could snap out of it and I'd be awake & have tons of energy. I would WANT to clean something or work out or whatever. This feeling would last most of the day too.
Heroin also gave me that kind of energy. except it was shorter lived. but just as good.

I first tried bupe in 2015ish. Some one gave me a strip and told me to only take a quarter of it.
So I mistakenly took that quarter on a morning before work, with my usual tramadol dose.
And holy shit, I could NOT stop nodding at work. It just kept going & going too, for hours.
It wasn't very euphoric but it was heavy as fuck. Everyone kept coming up to me and asking me if I had got enough sleep. I was like.. "uhhh.. oh yeah, I didn't". lol
It didn't give me energy that day tho.

Flash forward a few years & I started buying subs in between heroin grabs & that's when discovered that it gave me some energy comparable to tramadol & heroin. Although it was mild, it kept me out of withdrawals longer & so I thought "wow, fuck it, I can live with a more mild sense of energy if it means not dealing with withdrawals anymore". But boy was I wrong. There was no "wow, I want to clean so bad right now" or "I wanna go for a walk & listen to the same songs over & over again (and I would actually enjoy it!!!)" type of motivation on bupe ever though. Even when it did have me feeling somewhat good, I still felt mostly lazy.
I loved working out really hard to get that next-day sore body feeling, where I could just take more trams or heroin & make it go away.
Where as if I try to work out on bupe, I'll feel that next day soreneness no matter how much bupe I take.

Flash forward another 5-6 years & having taken bupe every day at various dosages, it no longer provides anything even CLOSE to tramadol or heroin. In reality, it just makes me heavy & tired. Where as tramadol and heroin may given me nods, but they didn't make me "tired" or too heavy feeling to do anything like bupe does.
Even at 1mg a couple times a day, that 1mg is still hanging around in your system til the next day, so taking more the next day just causes you to build up closer & closer to the ceiling effect unfortunately.

Bupe + tram were a great mix, but weirdly, the last chance I got to use tramadol was a year ago & it did absolutely nothing.
And now a days I'm wishing I could be on any other opioid.
Now the only way to get anything remotely nice out of bupe is if I take a few days off, which is almost impossible since I'm some one who likes to take something every day.

In a way, it was like the "system" said here, have opioids for awhile. Then took them away from me & put me on a more potent, longer acting & less useful opioid. And now I'm trapped on that because I've been opioid dependent for so long.
But looking back at it now, minus the times I was in withdrawal, I actually functioned BETTER on full agonist opioids than I do now on state approved "opioids".

 

[crzydiamond]

You may be right about not me not metabolizing tramadol well.

In general, I have an absurdly fast metabolism with most things.

But I don’t think i metabolize codeine well either. Never really could feel much difference between Tylenol with codeine and Tylenol without codeine. I read somewhere that like 25% of people can’t metabolize codeine well or at all.

I would get a lounge around lazy high from tramadol but not what you describe.

It’s fascinating how some drugs affect different people very differently

Bupe really gives me that “get things done” energy. And i get like super pinned eyes on it. (I have a long history of opiate use including stints in a methadone clinic —which incidentally *that* made me sleepy and that was heavier )

If anything, on bupe I sleep lightly, more so than ever in my life. It’s not at all sedating to me. At the end of a day at work I am tired and can sleep, but I don’t dose bupe after like 3-4 pm simply because of the way it gives me the up energy.

I had a hard time sleeping at all when I first took it. I had to take clonazepam or hydroxizine to even get sleep.

I like the bupe cause I feel amazing throughout the day at work, I’m moving around most of day and interact with people and it is like how I always felt more like talking to people when high on heroin.

So my work days are fun.

And yes I realize bupe has an insanely long half life but after like 30odd hours half is out of my system so dosing 2-4 mg a day isn’t going to put me to ceiling.

Even on methadone with that half life, if you were dosing 50 mg daily your actua blood level was like 75 -80 mg from buildup.

But it does process out as well it doesn’t all just sit there.

And sometimes I don’t take any bupe. Like today I woke up still feeling good and was off so didnt even remember to take any and I realized at like 1 pm I was fine.

Just interesting stuff

But for instance , my mom gets almost wired on Benadryl. But it knocks me out.
Maybe I got lucky n got some weird genetic mutation that makes bupe the opposite for me

Anyone else get opiate energy on bupe to the point it feels like a heroin high ?

 

[DeathIndustrial88]

Yeah what's weird too is I never felt jack shit from codeine, or at least I didn't perceive to.
Yet tramadol rocked my world. I *think* tramadol & codeine are metabolized by the same enzyme, so this makes no sense to me.

Drugs are incredibly weird.
I hated hyodrcodone & opiates in general as a teenager. Every time I tried them, I just felt sick & some times puked. Couldn't understand wtf ppl liked about them so much.
Now I'd thoroughly enjoy some hydrocodone right about now. lol
I was the same when I first discovered bupe. Well actually when I discovered it for like the 3rd time.
But I guess the 5 years I've spent on it everyday probably make a huge difference too as far as tolerance goes.