My answer is yes. Always do your own research. Tramadol is a combination opiate and the properties of an SNRI (antidepressant) and is very successfully used to treat both pain and depression (off-label), with no where near the addiction rate of other opiates.
What does this mean in terms of RLS and withdrawing from a DA? An SNRI, while great for depression, is terrible for the “symptoms” of RLS because it is a dopamine antagonist, essentially the opposite of a dopamine agonist. So instead of a tendency to down-regulate our receptors as the dopamine agonists do, Tramadol may very well have the tendency to up-regulate them, which is unbelievably great should it be the case. Here’s the proof, kind of: researchgate.net/publicatio...
I QUOTE: “Autoradiographic analysis of [(3)H]7-OH-DPAT and [(3)H]raclopride binding revealed a significant up-regulation of dopamine D2 and D3 receptors in the rat nucleus accumbens upon repeated treatment with tramadol. “
Wow, wow, wow, this is so great for RLS…if you’re a lab rat 😅
Could Tramadol be a gift from above in terms of RLS and withdrawing from a DA? I think so. Maybe the protocol for withdrawing from a DA should simply be low dose (100mg ?) Tramadol plus magnesium glycinate by day and ferrous bisglycinate by night, every night, not every other night. See BooFoo71. Then three months out from the DA start tapering the Tramadol. How low can you go 🤩? 50mg?At this point you can consider Gabapentin if you want to go lower or get off the opiate completely. Amen
Amen Amen. We all need to do our own research and stop praying for the RLS medical community to save us. The cavalry isn’t coming people. We are the cavalry.
MY FINAL WORD: Tramadol is great for a short term “treatment” and “relief” of RLS. I truly believe used properly it will not only help people get over the DA hump, but will up-regulate what the DA down-regulated. After putting the word Tramadol in the above search box, I saw this scenario play out again and again. See my reply to RestlessInLondon for my conclusion and ultimate advice: healthunlocked.com/rlsuk/po...
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I quote: Tramadol is a centrally-acting opioid agonist and SNRI (serotonin/norepinephrine reuptake inhibitor) used for the management of moderate to severe pain in adults.
There you have it. Tramadol will help with not only pain, and RLS and depression, but maybe it will help up-regulate our down-regulated dopamine receptors. That is so frickin other-worldly to me I wish someone would find evidence to the contrary. Please 😵💫
I’ve attached that link to my post for clarity. Thank you. Do you want to delete your reply then really think about this deeply and help me sort this out and whether there’s some serious drawback to Tramadol I’m missing.
It’s complicated. You really need to read what I wrote. And meditate on it. And understand what RLS truly is (lousy D2/D3 dopamine receptors), what DAs do to those receptors (down-regulate them) and what SSRIs/SNRIs do to them (up-regulate them as painful as that may be).
I understood from your earlier posts that iron nightly worked well for you? What happened? Or does the iron still work well for you and are you trying to help others?
Yes, iron is still working like a charm. Thank you for asking. It’s a bit more complicated. Here’s my explanation to RestlessInLondon. Augmenting on Tramadol is all but impossible.
“Hi Restless, your situation is very interesting and what I would expect once stopping Tramadol after being on a low dose for a year. I don’t believe you were experiencing augmentation, but rather tolerance to the opiate part of the Tramadol and suffering due to the dopamine antagonist (called SNRI) part of the Tramadol . See my recent post.
In other words, the Tramadol did not down-regulate your receptors as the DAs do, but very possibly just the opposite. I’m realizing that Tramadol is not an acceptable “long term” solution to RLS. Just too painful. You use it for a short period to come off the DAs (or some other stronger opiate you want to come off of) and to up-regulate your receptors, all at the same time ✨. Then switch to codeine as you have successfully done.
There’s no way you could stop a DA then be sleeping well two days after stopping it by just taking codeine. So it may have felt like augmentation, but in reality what you felt was no different than say someone on Effexor (also an SNRI) who is pre-disposed to RLS. Alas, no pain, no gain. You suffered, but in the process you helped your dopamine receptors and that is why you “feel better than you have in ages.”.
Tramadol should be used more like an antibiotic, only it’s an anti-da 😐 Tramadol up-regulates what has been down-regulated by the DA (say over a 3 month period), provides more than decent relief from RLS, but then it’s time to move on before your brain develops tolerance to its pain relieving qualities and you’re left with the uncomfortable dopamine antagonist portion of it.
I see you have a healthy ferritin level. Please try iron anyways - one time 🙏. Try it exactly this way. Take around 50 mg of ferrous bisglycinate around two to three hours before bed, on an empty stomach. If you’re like me, you should feel the RLS diminish greatly in an hour or two. Then proceed with the codeine as needed. If the iron did nothing for you then drop it, or keep taking it in the hopes that raising your ferritin even higher will help in the long run. If it does help then you just scored a home run!”
No need to copy-paste things I/we can easily find and I had read already. I think you jump to conclusions without really understanding. Our bodies are a bit more complicated than you seem to think. But that is just my view.
Tramadol is one of a handful of drugs doctors are willing to prescribe for RLS and that provides decent relief. So it’s ultra important to the RLS community. I didn’t come to a simple conclusion. I came to a complicated one you might not understand. Kaarina saved the post, so did several other people. Do you have any questions for me or are you here to just be you as usual? I see your conclusory, unhelpful comment got four likes from the old guard out there? Sad
I have a 40+ year career in science. Not neurobiology, but did touch upon it. And hence I know a tiny bit about scientific research are - more importantly - how to read and interpret papers. And maybe you are right, but personally I don’t think so. I wish you were though. Then we wouldn’t stay long on this forum, it could be deleted.
I didn’t say it was a cure for RLS Lotte. I’m saying it’s a darn good bridge post DA and that it does not down-regulate the dopamine receptors as the DAs do. Bridges save lives and I have a feeling Tramadol has saved countless lives. If you don’t think I’m accurate how about you enlighten us. You have 40 years in science -show off a little instead of just putting down my research. Terribly unprofessional don’t you think?
Plus, I don’t want to see Tramadol demonized on here on the false assumption it causes augmentation. I think we need to stop telling people that. Kaarina, are you out there? Do you have an opinion about telling your members that Tramadol causes augmentation?
Tell them about the soap under the sheets trick too. Just think how much pain and suffering could have been prevented if we hadn’t waited until the medical community decided that DAs were bad for RLS. AND, it’s not what I’m saying, I’ve attached articles that say Tramadol (an SNRI) upregulates dopamine receptors - just the opposite of augmentation. Did you read the articles? Did you see my name on them?
How about you find a couple articles where RLS experts claim that Tramadol causes augmentation. I LOVE doing medical research and I only found one article, based on one case study. It’s really only us on here that make that shameful false claim - as far as I can tell? Can someone, anyone, prove me wrong. I’m no fan of opiates. I’m a fan of saving lives and ending suffering.
My experience with opiates ( Targinact ) is extremely positive. After eighteen months, no dependency, no increase in dosage and it eliminates rls for 12 hours.
I am thrilled for you. I see an iron infusion did nothing for you. Imagine the DA at a center point with several lines jutting out like a sun. They represent journeys away from the DA with no return. You found one, yay. I’m looking for one that expedites our dopamine receptors return to baseline, which time alone will usually do. The problem is that as you stop the DA and try to return to baseline it is too painful a process without some other drug. Hence, not only do I want a substance that will hasten the receptors return to baseline, but also provide relief along the way. I have looked for just such a substance for over 10 years, here and there, nothing major. That substance is Tramadol. In my opinion it’s not meant for the long run as the Targinact is. I think it will be wonderful at getting people back to baseline post DA, with much less suffering. Once there, a person can make rationale decisions as to how they want to control their RLS going forward.
Well, hopefully no one will listen to you or that utterly false assertion that only we on here are claiming and NOT the medical community, nor the RLS experts.
I used tramadol to get off Ropinirole. It helped a little, although cannabis helped more.But, even though it up regulated my D2 and D3 dopamine receptors, my RLS was still classed as very, very severe.
I switched to Oxycontin and pregabalin and wasted 5 years with very severe RLS. So tramadol did not help.
I had an iron infusion. No change.
Your research and theories are interesting BUT, as we learn time and time again on here, one size does NOT fit all.
Your ferrous bisglycinate tip helps many, but it does nothing for others.
It's the same as Eryl's low carb diet. It works a treat for some, but does nothing for others.
Iron infusions definitely improve RLS dramatically for those whose RLS is caused by decades of anaemia. I personally know three people. But they don't work for around 40%. We don't know the reasons for that. Perhaps because dopamine receptors have been damaged by years on DAs. Perhaps because poor iron uptake is NOT the cause of RLS for them.
In my case, and those with spinal injuries, it's more likely to be damaged spinal column preventing dopamine flow.
The fact remains that we do NOT know for sure as there have not been enough human trials or research. Millions more in funding is required.
What we do know is that dopamine agonists are very bad news. You are extremely lucky you have never gone down that route.
We also know that ferrous bisglycinate helps some, but not all. Similarly, a low carb diet helps some, but not all.
Your theory on tramadol has been tested on rats. And yes, tramadol up regulates D2 and D3 receptors so it MIGHT reset some people's receptors. But as dopamine agonists can cause permanent damage to said receptors, it won't work in the same way for everyone.
Until human trials are carried out, extensively, we remain reliant on the human trials out there involving lots of participants.
I note what you say about tramadol and will not in future say it definitely causes augmentation. There is only one case study. However, if it up regulates D3 receptors, that could cause increased RLS for people.
And Kaarina's role on the forum is as a moderator. She does not add research or comments. Every moderator on Health Unlocked is there to keep the forum running smoothly, not to add comments or research.
I have always enjoyed debates with you, but it would be better if you didn't become so frustrated, and rude, when people express an opinion which doesn't match yours. If you remained positive in your views, without becoming rude or angry, people will listen. They may not agree, but they will listen and perhaps research further.
Jools it was a long time ago and i can’t remember who was involved it might have been Dr B or Dr Early or even Dr winkleman. They did a study on iron infusions on some people which worked their RLS disappeared. But after a while their ferritin levels dropped think it was 6 months for some cant remember how many then some a year others 2 years. It’s probably still out there on youtube most likely.
First, I’m not angry. I welcome attacks, They don’t make me look bad. About a dozen people have now saved my posts. That tells me they weren’t aware of these facts and should be. I knew about Tramadol being an SNRI a year ago but failed to post it on here. Till now. And the iron at night trick should be told to every newbie, if you want to be a leader on here and you’re one of the ones who spring into action every time someone comes on here. Your experience and mine are pretty much irrelevant, don’t you think? Like you said, I’ve never been on the DAs and you’re an exception because of your auto-immune disease. The facts are what they are and I’ll just keep trying to tell people these things myself. They have a right to know. OUR BRAINS ARE SWIMMING IN IRON - by day, with essentially zero stored iron. You’re too smart not to see the whole picture now. Our brains crank up the dopamine and iron because the “reception” is so darn poor. Both have potential deleterious effect when too high so there’s no way any of that heavy metal iron is getting stored any time soon. Mayo claims our “low brain iron STORES” are due to, most likely, our “down -regulated striatum dopamine receptors.” I couldn’t agree more. It’s a new era and the buzz word is up -regulation. “ And not only do people post-DA need this, we all do. Tramadol may very well be one way. Pretty exciting, no? EVERYONE, new and old on here, should understand these basic facts and act accordingly. Don’t you think?
Certainly. And I do tell people about iron as first line treatment. Here in the UK, iron infusions are not likely to happen on the NHS, so ferrous bisglycinate is a quick and easy way to go. However, most 'newbies' are on dopamine agonists and have been for years. Their dopamine receptors are likely damaged. Permanently. And thus unable to take up iron etc.And by all means they can try tramadol to get them off dopamine agonists.
But it remains the case that we all respond differently to different treatments.
Otherwise we would all be on a low oxalate diet/low carb diet etc and all have the same result.
The iron at night trick has to be described exactly as I do, not just “hey try taking some iron to raise your ferritin over 200.” You know this counselor. You don’t want to tell people about this potentially life altering therapy, nor should you have to.
I’ve taken Tramadol for about 9y to treat RLS and yes it works extremely well — initially!
However, over time its effectiveness diminished and my dose was gradually increased to 150mg from 50mg. That’s when I started experiencing some bad side effects. The worst side effect was involuntarily falling asleep for a few seconds. Especially dangerous when driving. Also, in the evening, before taking the medication, I had intense RLS sensations.
When I changed doctors, I was informed that this medication is not ideal for treating RLS because augmentation has been documented and apparently it happened for me. So, I was gradually taken off this medication over 6mo!!!
While everyone reacts differently to medications, I have to caution you about this drug. Despite being less controlled than oxycodone for example, this drug is highly potent and overcoming dependency from it is worse than overcoming dependency from a typical opiate. This drug affects 3 neurotransmitter systems in your brain and you will be going thru 3 withdrawals if discontinue it. Personally, I will never take that drug again. I’d rather live with RLS than go thru that again. Fortunately, there are better treatments out there!
Yep, not meant to be a long term treatment in my mind, anymore than say a combination of Effexor (an SNRI) and codeine. The codeine will lose effectiveness and then you’ll be left with the agony of taking a dopamine antagonist. SSRIs and SNRIs are a lot of times what drives people to take DAs in the first place. When your RLS worsened in your mid-40s what other drugs were you on, if any? Antidepressants? Calcium Channel Blocker? Any injuries?
I started off with DAs in my mid 40s. I was on them for about 2y. I’ve had RLS since childhood. Prior to that the only drugs I was on were ARBs for hypertension and Lipitor.
Tramadol and DAs are not optimal drugs for treating RLS and it is possible, though unlikely, that the DAs worsened my RLS. I think the only reasons they’re prescribed is because they are less tightly controlled.
But one always has to approach drug treatment with foreknowledge of the side effects because all the agents currently at the disposal of doctors are all potent medications.
The heart medications likely worsened the “symptoms” (not the receptors) of your RLS because they too tend to antagonize dopamine and might be what drove you to the DAs, which very likely down-regulated your receptors. However, if you were taking the statin during this time it may have acted as a counter weight to the drag the DA put on your receptors.
Wow, we’ve known from reports that statins and ARBs worsen the symptoms of RLS, but here’s why for the ARB. It is a potent D2 antagonist. pubmed.ncbi.nlm.nih.gov/259... You may have suffered while on it, but theoretically it should have upregulated your receptors.
I quote: “High doses of simvastatin upregulate dopamine D1 and D2 receptor expression in the rat prefrontal cortex: possible involvement of endothelial nitric oxide synthase”
So for sure if you’re a lab rat your dopamine receptors are up-regulated by Lipitor.
Wow!!! This is shocking news for me! My understanding was that these medications were mostly benign! I was on fairly large doses for both statins and several ARBs! (Mostly on olmesartan and atorvastatin)
Thank you for all this information !!
Incidentally, I am currently on another medication - Zepbound (Tirzapetide) for weight loss. This medication DEFINITELY makes my RLS worse even though I'm on 5mg oxycodone and 1400mg of gabapentin. My daughter who just finished her pharmacy degree informed me that GLP-1 agonists also antagonize dopamine receptors. So for 2-3 days after my weekly injections I have bad nights. For now I'll stick with this medication because the positive impact on my health has been huge.
It almost seems that most pharmaceuticals fix one problem and cause a few other problems.
I know where you’re coming from. I’m on a proton pump inhibitor after 10 years of saying no. I have a terribly annoying condition called EoE as well as reflux which results in food getting stuck in my esophagus upwards of 5x a day. Dilations only help temporarily. I am sooo much better with the PPI. I used to be on 25mg of iron a night. Now I’m on 50+. It’s ok, we do what we must, right Niko 😅
I was on Pramaprexol for about 17 years and augmented. I went through a year of hell trying many different drugs to help the severe RLS.
Tramadol (50mg) gave me great relief for several weeks, then less and less. Do, I increased to 100 mg., which worked better for a few more weeks. Then I had to increase to 150 mg, and it become less effective after a few short weeks. I was scared to continue to increase because it made me feel so doped up/buzzy every night and I didn't like the daytime side effects. I assumed I augmented on Tramadol, so I kept searching for other solutions.
Thanks to Jools and this forum, I contacted Dr. Berkowski and got Suboxone(buprenorphine), which has been a life saver for me. I take .33 mg nightly (1/6th of a film) and it works perfectly so far, with no noticeable side effects. I started with 1 mg and kept reducing over time to take the minimum. This is the only drug I take and I would like to ween off, but still haven't discovered a natural solution.
Is it your theory that if I returned to Tramadol, this drug could actually repair the damage to my dopamine receptors over time?
Steve, you were already on Tramadol for six months after other drugs failed to relieve post-DA RLS. And I saw you did a cold swap to Kratom for a month, then back to Tramadol. At any point did it seem like you had returned to baseline RLS? To me, that’s the point of Tramadol, to get you back to baseline quicker so you can regroup and chart a new course.
I think maybe you did return to baseline and your baseline is unacceptable and not something you can treat with magnesium by day or iron at night as some of us do. You’re in an enviable position in that you have a sure thing in your back pocket. If you think you’d like to do another reboot - meaning stop the strong stuff and see what baseline feels like and give yourself another shot at a low drug, more natural approach to dealing with your RLS, I say go for it. Sub out Bup for Tramadol. Not sure how much? 100mg? You can always go back to Bup. If several months go by and the Tramadol seems to be failing that’s a good sign and time to stop the Tramadol and switch to Codeine. Please don’t waste that opportunity and run to the Bup. Give yourself a few days, just a few days 🙏, on low dose codeine. If you’re miserable and not sleeping you will have your answer and you can run back to Bup with my blessings and feeling good about your choice without regret.
RestlessInLondon did this and in two days he was sleeping and feeling great on the Codeine. Mr. London owes me an update however. 🫤 Lastly, why did you go on a DA in first place at such a young age? Were you on an SSRI or tricyclic or heart medication? Sports injury?
And it never hurts while on Tramadol to take magnesium glycinate by day and ferrous bisglycinate by night. If you feel really daring you might want to try berberine by day as well.
For a feel good story that is quite similar to yours, pay special attention to RKM7:
I have always had RLS as far back as I can remember, but it was manageable. I would kick for the first 30 to 60 minutes at night, but then fall asleep and sleep fine, waking rested.I was put on CPAP after a sleep study, due to frequent nightly urination. At a follow up visit, I checked the box on a questionnaire asking me if my legs were irritated at night. Without much discussion or an end game, the sleep doctor prescribed Miropex. I wasn't a good advocate for my own health and very busy at work and with family life. So, I just started taking it, gradually increasing the dosage until it simply stopped working. Then the hell came.
If my RLS baseline is back nearly 20 years ago when I could easily live with it, I am not remotely close. If I take a Suboxone dose too small (or have too much sugar or beer near bedtime), my legs are crazy.
I have never tried low dose codeine, but why is that a better alternative to Suboxone? Is it because you believe Tramadol or Codeine can help heal the dopamine receptors, but Suboxone won't?
I should explain a little more. Tramadol is different from other opiates. It is structurally similar to Effexor and Codeine, both. You could literally make your own home brew Tramadol by combining low doses of the two. Then after about three months you drop the Effexor which was probably starting to overtake the Codeine anyways. Then you’re left with up-regulated receptors and the pain relieving qualities of codeine. We know from ONE article that Tramadol up-regulates the receptors. We know from dozens of articles that drugs like Effexor up-regulate dopamine receptors. Drugs like Effexor are just too painful for us with RLS.
We need to find weaker, more natural, more short acting dopamine antagonists that we take on and off for a lifetime, along with other great things like anaerobic exercise and intermittent fasting. Fun, rewarding and receptor up-regulating. Eryl is a good example, as well as ChrisColumbus, of going au-natural. Slow and steady wins the race. Oy, such a corny cliche 🫤
Anyways, if your baseline is pretty good, as you say, then codeine should suffice. And that’s why I told you to also take magnesium by day because it seems to be a much weaker dopamine antagonist that won’t affect your sleep. GreekStudent went from DAs to Gaba and magnesium to just magnesium. That’s my hope for you. And if magnesium doesn’t quite cut it, take some ferrous bisglycinate before bed, no matter how normal your ferritin is. Everyone’s serum brain iron (not to be confused with ferritin) drops at night, along with dopamine, and we get symptoms of RLS then, as opposed to during the day, when these levels are higher.
Here’s RestlessInLondon. He seems to have successfully worked his way from DAs to Gaba like drugs to Tramadol and now just codeine. I hope he keeps going 🙄 healthunlocked.com/rlsuk/po...
The member RKM7 was on DAs for 15 years and here’s her recovery story:
RKM7 profile imageRKM7Hidden 2 years ago
You’re back!!! It’s great to read your post!!
Thanks so much for your encouragement and advice! I remember noticing that I had good nights when I took the iron and then bad nights when I didn’t take it. You’re advice to take it every night made sense to me and It has made such a difference! I can only hope that others on this site will try this approach!!
I just completed 3months of berberine so as you have advised, I’ll take a month off. Yes, my cholesterol has come down too!! I’m thrilled!!
I also continue with fasting overnight and that helps! Whenever I eat later in the evening or have sugar in my diet the RLS acts up again. I would still be suffering every night if you hadn’t recommended these changes!
I plan on slowly reducing my Gabapentin dose over time. I’m hopeful that I will only need a lower dose or maybe none at all.
Love your quote!! How true!! I’m forever grateful to have found you!! I hope you’ll always know the difference you have made in my life! I hope to stay in contact with you here whenever you check back in. 💕
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