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  • BDD Moderators: Keif’ Richards

Opioids Tramadol is a Serotonergic painkiller

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BizMarkie1000

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Mar 25, 2026
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I've been on Tramadol for 6+ years for un-relenting back pain that does not improve with YEARS of physical therapy. This highly resonates an old family problem: GALLSTONES.

Now, Tramadol is starting to show signs of "tolerance". It used to have a very therapeutic antidepressant effect.

I asked my scumbag doctor to replace it with a more conventional painkiller like percocet (which I've successfully take before - NO WITHDRAWAL WHATSOEVER!!!) But these doctors care more about losing their mansions than facing a wrongful death lawsuit. (I'm NOT suicidal, but I am considering legal action).

So I figure this: Since it basically sucks the serotonin out of your Neurons, this leads to depletion of L-Tryptophan (not the cheap 5-htp shit).

I want to start taking L-tryptophan daily to replenish my body's supply of this vital amine precursor to serotonin. I have nothing left to lose.
 
You probably need a tolerance break.
This happens with all opioids.

I wouldn't say it's "sucking the serotonin out of your neurons" either. It's a very weak serotonin releaser & serotonin & norepinephrine reuptake inhibitor. It's metabolite O-desmethyltramadol is responsible for most of the effects, probably even the antidepressant effect.

All opioids can raise your serotonin levels in some way honestly. Some are just better at it than others. That's why there's always a slight risk of "serotonin syndrome" when combining any opioid with antidepressants.

I used tramadol for 10+ years & it kept it's magic until I started using heroin. And then it stopped working.
You most likely won't get the same antidepressant effect from oxycodone or hydrocodone. I know I don't. I prefer tramadol over the codones any day.
Of course, when I was on tramadol though, I had to withdrawal at the end of every month, which would reset my tolerance until the following month when I could get the script again. So that's probably why it kept on working for me.

I mean, in a sane world, a good doctor would just supplement you with some extra percocet on top of your tramadol for "breakthrough pain", but we live in a retarded world now full of opioid hysteria, so people gotta feel lucky that they even get what they can get. Shit I'd love to be on tramadol.
 
On TOP of being an opioid, Tramadol is ALSO an SNRI (Serotonin/Norepinephrine Reuptake inhibitor) which is a fancy way of saying it FLOODS the brain with Serotonin and Norepinephrine at much higher levels than even a healthy, non-medicated person needs to maintain enough reward and motivation to live a productive life.

That's how Tramadol resembles classical antidepressants like Effexor, Cymbalta, etc..
 
BizMarkie1000 said:
On TOP of being an opioid, Tramadol is ALSO an SNRI (Serotonin/Norepinephrine Reuptake inhibitor) which is a fancy way of saying it FLOODS the brain with Serotonin and Norepinephrine at much higher levels than even a healthy, non-medicated person needs to maintain enough reward and motivation to live a productive life.

That's how Tramadol resembles classical antidepressants like Effexor, Cymbalta, etc..
Click to expand...
Yes and it's SNRI effect is so weak that it's almost imperceptible.

What do you mean "is ALSO", as if I literally didn't just get done saying exactly what you just said. I just told you I've been on tramadol for 13 years & just described how it works, so I dunno why you're repeating that back to me.

If you don't believe it, go try Effexor. Effexor is almost structurally the exact same as tramadol. Except it feels nothing like tramadol whatsoever. Because it's an actual SNRI. Just because a drug is similar to another drug on a molecular level doesn't mean they're going to feel the same or even belong in the same class of drugs.

Benadryl is also a weak SNRI, but nobody calls it an antidepressant, because it's SNRI effect is incredibly weak.

Also, if your pain is as bad as you say it is, then why are you worried about having "normal serotonin levels for reward & motivation to live a productive life"? Because honestly, if your pain isn't being treated by something that affects those exact centers of the brain, then how you do you plan on living a "motivated productive life" while in constant pain?

Also, tramadol isn't just a weak SNRI, it's also a SEROTONIN RELEASER, like drugs like MDMA & methamphetamine. Except it's incredibly weaker at doing so than the latter drugs. Taking L-tryptophan or any sort of serotonergic substances with tramadol can put you at risk of seizure or serotonin syndrome.


In one breath you're saying tramadol FLOODS the brain with serotonin & in another breath you say it depletes it. So which is it? The only way you're gonna be deficient in serotonin is if you STOP TAKING IT.
 
I attended a Chronic pain support group. They told me most opioids are NOT serotonergic at all. (Except Tramadol and it's metabolite Nucynta).

Perhaps I was misinformed by them, but they seemed legit.

Anyway, I generally agree with you. I meant NO offense.
 
"Taking L-tryptophan or any sort of serotonergic substances with tramadol can put you at risk of seizure or serotonin syndrome."
Click to expand...
I actually brought this up face-to-face with a trusted doctor. (Because another Tramadol prescriber said to watch out for Serotonin Syndrome.

My trusted doctor said straight to my face: "Tramadol will NOT cause sert syndrome, and that other guy is just covering his own ass.

You can argue with me all you fucking want.

Fact is - I've known this trusted doctor face-to-face for over 10 straight years. I don't know you, and I cannot see you.

With all due respect - I will go with who I can see and hear in person.
 
BizMarkie1000 said:
I attended a Chronic pain support group. They told me most opioids are NOT serotonergic at all. (Except Tramadol and it's metabolite Nucynta).

Perhaps I was misinformed by them, but they seemed legit.

Anyway, I generally agree with you. I meant NO offense.
Click to expand...
All good then. I see you're new here, but some times people on here can be really difficult & condescending, so my bad thinking you were trying to be condescending toward me.

Well they're only partially correct. The healthcare industry gets a lot of things wrong. Even the "experts". Shit, America said Tramadol wasn't even an opioid at all for over 30 years & people believed it. That's how I use to get so much of it.

Anyway, back to the topic though. While it's true that tramadol has it's own unique weak SNRI effect, the serotonin aspect can be seen in many opioids. For example : Tramadol, Tapentadol, Pethidine, Methadone & Fentanyl

Some of the science around it is still murky though.

pubmed.ncbi.nlm.nih.gov

Opioid analgesic drugs and serotonin toxicity (syndrome): mechanisms, animal models, and links to clinical effects - PubMed

Drugs may cause serotonin toxicity by a number of different mechanisms including inhibition of serotonin uptake and metabolism, increased serotonin synthesis and release, activation of serotonin receptors, and inhibition of cytochrome P450 oxidases. Some drug interactions involving opioids can...
pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov


Here's a case of some one getting serotonin syndrome from one dose of Buprenorphine. Even though no clinicians recognize buprenorphine as having any effects on serotonin.


pubmed.ncbi.nlm.nih.gov

Serotonin syndrome triggered by a single dose of suboxone - PubMed

Suboxone (buprenorphine/naloxone) is an oral medication used for the treatment of opiate dependence. Because of its mixed properties at the opiate receptors, buprenorphine has a ceiling on its euphoric effects. We report the first case of serotonin syndrome caused by buprenorphine and review...
pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov


So I'm inclined to believe that most opioids cause their euphoria & "feelings of well-being" not only by raising dopamine, but by raising all 3 main neurotransmitters at the same time, just to varying degrees depending on the opioid.

But if you're worried about serotonin depletion, I think dopamine depletion from chronic use of opioids should also be something to worry about, cause dopamine plays a bigger role in reward & motivation than serotonin dose.
 
BizMarkie1000 said:
I actually brought this up face-to-face with a trusted doctor. (Because another Tramadol prescriber said to watch out for Serotonin Syndrome.

My trusted doctor said straight to my face: "Tramadol will NOT cause sert syndrome, and that other guy is just covering his own ass.

You can argue with me all you fucking want.

Fact is - I've known this trusted doctor face-to-face for over 10 straight years. I don't know you, and I cannot see you.

With all due respect - I will go with who I can see and hear in person.
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You go for it bud!

Last year my doctor told me I had a fungal infection & prescribed me an incredibly expensive antifungal med. Nothing changed, so I saw a dermatologist & it turned out to be bacterial, not fungal.

I don't care how long you've known your doctor or how well you approve of him, that does not make him infallible or not ill-informed. I literally just linked you to the NIH saying the exact opposite.

Serotonin Syndrome is rare & I never encountered it much in my 13 years on tramadol, but it's still a risk.

Your doctor is an idiot. And you ARE very well misinformed. Especially to come on here & say tramadol FLOODS THE BRAIN WITH SEROTONIN & then turn around & say "but it won't cause serotonin syndrome!".... Contradictory statements right there. And now you are just coming off as condescending, so go figure your shit out yourself then.


Yes in some cases people can be on both tramadol AND an SSRI & be fine. Especially if the dose of tramadol is low. But if your tolerance to it is high, I imagine you aren't playing around baby doses of tramadol. And yes serotonin syndrome is absolutely a risk of taking tramadol. That doesn't mean it will happen, but to flat out say it can't cause it is your doctor lying to you. If you wanna trust a LIAR, then you go right ahead dude.

I'm sure the guy who got Serotonin Syndrome from buprenorphine in this case was also told buprenorphine doesn't cause SS.
pubmed.ncbi.nlm.nih.gov

Serotonin syndrome triggered by a single dose of suboxone - PubMed

Suboxone (buprenorphine/naloxone) is an oral medication used for the treatment of opiate dependence. Because of its mixed properties at the opiate receptors, buprenorphine has a ceiling on its euphoric effects. We report the first case of serotonin syndrome caused by buprenorphine and review...
pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov


Oh here's this for you as well -

Serotonin Syndrome Associated With Tramadol - PMC

pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov

Most psychiatrists are aware of serotonin syndrome with antidepressants but less likely to attribute it to other classes of medications such as analgesics.4 This is the first reported case in which serotonin syndrome was associated with tramadol alone without concomitant use of other serotonergic medications. Clinicians frequently prescribe tramadol as an analgesic since it is not considered a controlled substance. Awareness of its serotonergic effect is important in avoiding potential side effects and unwelcome interactions with other medications. Additionally, recognition is important regarding tramadol and its potential to cause serotonin syndrome, especially in light of concomitant usage with other serotonergic medications such as antidepressants.

And this was written along time ago, when doctors still thought tramadol "wasn't an opioid", you know because doctors are so correct about everything all the time & would never lie.

More

And more

Serious Reactions with Tramadol: Seizures and Serotonin Syndrome

www.medsafe.govt.nz www.medsafe.govt.nz

And more

Tramadol Pill Alone May Cause Serotonin Syndrome - PMC

pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov

Ridiculous that you get on here & argue with me & say tramadol is a serotonergic drug (more so than it even is) & then try to turn around & argue with me that it can't cause serotonin syndrome. Guess what bud? Anything that increasing serotonin has the potential to cause serotonin syndrome. You're literally on a forum asking for advice & then saying shit like "well I can't physically see you, so how can I trust you?"....Maybe go ask your doctor for advice then if you don't want to hear the truth.

I've taken tramadol with methamphetamine & dextromethorphan & never had serotonin syndrome. Does that mean I'm gonna go around telling people it can't cause SS? Absolutely not, because the obvious fact of the matter is that IT CAN, as shown by all the links I just gave you, which come straight from the National Institution Of Health. You know, a government-run website.

YOU may never get serotonin syndrome, but to say it CAN'T or DOES NOT cause serotonin syndrome in any circumstance is just flat out lying.
 
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I did NOT come here to make enemies.

My pain is sucking the life blood out of me, which makes me abrasive and irritable.

But it is NOT PERSONAL!

I'm sorry that I cannot control my temper sometimes. I know that millions of others suffer through needless pain that can make them just as much of a PRICK that I can be.

I do NOT want to be your enemy. AND, I appreciate you taking the time to link me with the NIH research. Taking that effort means a lot.

Perhaps, we can have a drink together one day? (Just saying - nothing bonds people better than a good drunken evening together!)
 
BizMarkie1000 said:
On TOP of being an opioid, Tramadol is ALSO an SNRI (Serotonin/Norepinephrine Reuptake inhibitor) which is a fancy way of saying it FLOODS the brain with Serotonin and Norepinephrine at much higher levels than even a healthy, non-medicated person needs to maintain enough reward and motivation to live a productive life.

That's how Tramadol resembles classical antidepressants like Effexor, Cymbalta, etc..
Click to expand...
More Serotonin really doesn't help much against depression for most people. If anything high serotonin levels lead to apathy, reclusiveness and a certain numbness to live. Being more numb can be preferable in some situations but I wouldn't say that's the ideal state one wants to live in.

From my understanding, Tramadol is particularly moodboosting at the "beginning" of usage (which can be quite a long time if you take low dosages or spread out your dosing schedule) because of the energy caused by Norepinephrine combined with the opioid and slight serotinergic effect.

To highlight my point that more serotonin certainly isn't always great, during opioid withdrawal you will see a huge increase in serotonin too. Note the fact that your pupils get dilated a lot during these moments, very similarly to when using LSD or MDMA. Sadly you will feel terrible instead of euphoric.
 
Serotonin biosynthesis goes kind of like this
Tryptophan ==> 5-hydroxytryptophan ==> serotonin

The first reaction is catalyzed by tryptophan hydroxylase, which is the rate limiting step of serotonin synthesis. Feedback inhibition occurs, where high levels of serotonin inhibit the enzyme.

The second reaction, by aromatic L amino acid decarboxylase is subject to a lot less feedback inhibition and other regulation.


What I am getting at, is that l-tryptophan isn’t as efficient at increasing serotonin levels as 5-hydroxytryptophan.

Also, I am unsure if serotonin reuptake inhibitors tend to decrease brain serotonin levels due to higher levels of serotonin utilization. It seems more likely that reported decreases in serotonin signaling downstream of SSRI/SNRI use are due to downregulation of signaling pathways, rather than simply by using up brain pools of serotonin (which are always going to exist in an equilibrium between synthesis and release; and SSRI/SNRIs aren’t going to affect the release as much as they will slow the reuptake).
 
You should slip a xanny in your doctor's coffee so he becomes retarded and gives you a script for everything.
 
What I am getting at, is that l-tryptophan isn’t as efficient at increasing serotonin levels as 5-hydroxytryptophan.
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If you prefer 5-htp, then God Bless! Different things help different people!

I did NOT come here to argue, or to be a prick.

Pain makes me such a prick... It's been YEARS since I had a woman. I need to get a hooker.
 
Is it just me? Or wasn't Bluelight originally hosted by Russia? I'm having the WEIRDEST Deja Vu....

(Feel free to correct me if I'm wrong... Not like I have a problem with who hosts it)
 
BizMarkie1000 said:
Is it just me? Or wasn't Bluelight originally hosted by Russia? I'm having the WEIRDEST Deja Vu....

(Feel free to correct me if I'm wrong... Not like I have a problem with who hosts it)
Click to expand...
Might have been .ru but my memory not that consistent as i would like. No can t find a reference, it has been .org and .nu which was a island somewhere. domain names don t mean anything really. Though the way that island took advantage of the i*net hype stuck. Is it still above water i wonder ? But welcome on this site.

https://en.wikipedia.org/wiki/.nu

But the problem you describe interpreting messages is universal, hard to write a consistent text especially without eye contact. Reoccurring phenomenon for me even reading back thing s i wrote myself. But the problem you describe pain and such also.

Just lost my login what the, but any exp with Kratom ?
 
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Yeah.. I use Kratom (Wild Red Bali) - Only on days withOUT any Tramadol. Kratom NEVER MIXES with Tramadol on the same day!

Maybe you might ask me if I use Cannabis? I had to stop Cannabis because it was virtually worthless against pain (PLUS causing Insomnia, weird YELLOW vomiting, panic attacks, and a generalized "uncomfortable numb" feeling all around).

But I don't judge ANYONE who receives benefit from Cannabis! Do what you gotta do! We're all wired differently in our brains.
 
However, lately - my level of pain, despair, stress, and anxiety have been raising my blood pressure.

Am I wrong for quitting Cannabis? Am I being too "Self-righteous" about this?
 
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