Tianeptine withdrawals - why so horrible?

[jambabomba]

Okey, there was threads and messages on this forum about tianeptine's withdrawals and how they are horrible. Some even said that heroine withdrawal was nothing compared to tianeptine.

So I started to thinking what could it be on neurochemical/pharmacological level what causes this? Is there component of NMDA overexcitation combined with opiate withdrawal so simultaneously excitotoxicity like in benzo withdrawals + opioid withdrawal pains or what is the mechanism that could make it worse than heroine as people claim?

 

[AlsoTapered]

I think you are overthinking it. Since it has DAT activity and opioid activity, I guess it's like stopping a stimulant and an opiate at the same time.

 

[CmonYouShouldKnowBetter]

Tianeptine is a dirty opioid. By "dirty" I mean it has more than one mechanism of action. So when you WD you are hurting by way of opioid, serotonin, and GABA.

 

[Skorpio]

Tianeptine is a dirty opioid. By "dirty" I mean it has more than one mechanism of action. So when you WD you are hurting by way of opioid, serotonin, and GABA.

Do you have any sources for the GABA activity? I always thought the purported SSRE effects of tianeptine were a smoke screen because people didn't understand tianeptine was an opioid until pretty late in the game.

I always thought it was rough because it's short acting, so withdrawals kick in hard and fast.

 

[Nas47]

yes i heard that too-bad withdrawl for the misaerable effect.bad stuff

 

[CmonYouShouldKnowBetter]

yes i heard that too-bad withdrawl for the misaerable effect.bad stuff

I think its great stuff! I used it often. I simply dose low and not more than once every few days. No WD or side effects

 

[CmonYouShouldKnowBetter]

Do you have any sources for the GABA activity? I always thought the purported SSRE effects of tianeptine were a smoke screen because people didn't understand tianeptine was an opioid until pretty late in the game.

I always thought it was rough because it's short acting, so withdrawals kick in hard and fast.

Metabolomic profiling relates tianeptine effectiveness with hippocampal GABA, myo-inositol, cholesterol, and fatty acid metabolism restoration in socially isolated rats - PubMed

Metabolomics revealed several dysregulations underlying CSIS-induced depressive-like behavior and responsiveness to Tian, predominantly converging into NMDAR-mediated glutamate and myo-inositol signalization and GABA inhibitory pathways.

pubmed.ncbi.nlm.nih.gov

Antiallodynic effect of tianeptine via modulation of the 5-HT7 receptor of GABAergic interneurons in the spinal cord of neuropathic rats - PubMed

Although tianeptine, an atypical antidepressant has been reported to have antinociceptive effects, the mode of action is different from that of tricyclic antidepressants despite structural similarities. We examined the antiallodynic effect of intrathecal tianeptine in neuropathic pain rats and...

pubmed.ncbi.nlm.nih.gov

Tianeptine modulates synaptic vesicle dynamics and favors synaptic mitochondria processes in socially isolated rats - Scientific Reports

Deregulation of synaptic function and neurotransmission has been linked with the development of major depression disorder (MDD). Tianeptine (Tian) has been used as antidepressant with anxiolytic properties and recently as a nootropic to improve cognitive performance, but its mechanism of action...

www.nature.com

 

[Skorpio]

Metabolomic profiling relates tianeptine effectiveness with hippocampal GABA, myo-inositol, cholesterol, and fatty acid metabolism restoration in socially isolated rats - PubMed

Metabolomics revealed several dysregulations underlying CSIS-induced depressive-like behavior and responsiveness to Tian, predominantly converging into NMDAR-mediated glutamate and myo-inositol signalization and GABA inhibitory pathways.

pubmed.ncbi.nlm.nih.gov

Antiallodynic effect of tianeptine via modulation of the 5-HT7 receptor of GABAergic interneurons in the spinal cord of neuropathic rats - PubMed

Although tianeptine, an atypical antidepressant has been reported to have antinociceptive effects, the mode of action is different from that of tricyclic antidepressants despite structural similarities. We examined the antiallodynic effect of intrathecal tianeptine in neuropathic pain rats and...

pubmed.ncbi.nlm.nih.gov

Tianeptine modulates synaptic vesicle dynamics and favors synaptic mitochondria processes in socially isolated rats - Scientific Reports

Deregulation of synaptic function and neurotransmission has been linked with the development of major depression disorder (MDD). Tianeptine (Tian) has been used as antidepressant with anxiolytic properties and recently as a nootropic to improve cognitive performance, but its mechanism of action...

www.nature.com

These all talk about tianeptine increasing gene expression of GABAergic interneurons especially (and all cover different aspects of that, so it seems like a very robust hypothesis).

The second paper shows that this effect occurs through a serotonergic pathway (5HT7 receptors specifically), as the protein expression effects can be blocked with a selective antagonist.

None of these studies produce any evidence that tianeptine acts as an agonist at GABA A or GABA B receptors (I even looked at some relevant looking references).

However I think we are crossing paths as my question was focused at the ligand binding to receptor level, and your answer was at the circuit level.

This distinction is important to make, because it highlights two different ways to view a drug's action. Looking at receptor binding affinities is simpler and easier to parse, and often allows one to generalize about a drugs effects (especially immediate effects). Looking at circuit level changes gives the most accurate picture of how a drug achieves a given effect, but often cannot be generalized beyond the specific effect caused by a specific circuit (such as how that second paper talks about how the increase in function of 5ht7 postive GABAergic interneurons in the spinal cord being responsible for anti-allydonia effects).

 

[deficiT]

I believe it's a tricyclic antidepressant in addition to being an opioid, so similarly to tramadol it affects your norepinephrine and serotonin levels in addition to typical opioid withdrawal effects.

 

[beebs76]

Metabolomic profiling relates tianeptine effectiveness with hippocampal GABA, myo-inositol, cholesterol, and fatty acid metabolism restoration in socially isolated rats - PubMed

Metabolomics revealed several dysregulations underlying CSIS-induced depressive-like behavior and responsiveness to Tian, predominantly converging into NMDAR-mediated glutamate and myo-inositol signalization and GABA inhibitory pathways.

pubmed.ncbi.nlm.nih.gov

Antiallodynic effect of tianeptine via modulation of the 5-HT7 receptor of GABAergic interneurons in the spinal cord of neuropathic rats - PubMed

Although tianeptine, an atypical antidepressant has been reported to have antinociceptive effects, the mode of action is different from that of tricyclic antidepressants despite structural similarities. We examined the antiallodynic effect of intrathecal tianeptine in neuropathic pain rats and...

pubmed.ncbi.nlm.nih.gov

Tianeptine modulates synaptic vesicle dynamics and favors synaptic mitochondria processes in socially isolated rats - Scientific Reports

Deregulation of synaptic function and neurotransmission has been linked with the development of major depression disorder (MDD). Tianeptine (Tian) has been used as antidepressant with anxiolytic properties and recently as a nootropic to improve cognitive performance, but its mechanism of action...

www.nature.com

I took Tianeptine sulfate (25 MG of Tia Sulfate 3 times per-day) to successfully get off of Klonipin (Tapered down to .25 MG once per-day for 3 weeks before jumping off - was as high as 2MG 3 times per day for a year). The last time I did this without Tiapneptine, the withdrawals were horrible. It was MUCH MUCH more tolerable when using Tianeptine for 3 months after the jump off. I did have a bit of heightened anxiety the first 3 days, the first few days I felt a faster heart rate, but I was able to sleep at night and overall would rate the withdrawal from Klonipin like a "2" on 1 to 10 scale when before it was like an "11!" So I think there has to be something in the Gaba department with Tia. There is no way this was a placebo. At the end of 3 months I tapered down on Tia to 12.5MG 3 times per day, and then 12.5 MG twice per day, and then totally jumped off of that. Tiapentine needs to be looked at for Benzo Withdrawal treatment IMO. Note : I did take Gabapentin 400 MG per day for the first 2 weeks after jumping off of Klonipin with the Tia Sulfate. I used Ibuprofen and Melatonin for sleep the firs tfew weeks. I also took Magnesium 500 MG twice per day. Other than that. that was about it, and I feel like I have totally recovered form Benzo use.

 

[negrogesic]

I have done a LOT of drugs, and have experienced acute withdrawal from a wide array of opioids (from high dose heavy duty narcotics like methadone, oxycodone, IV heroin, fentanyl, poppy pods, to lighter stuff like tramadol and kratom), and from my extensive experience with tianeptine, I would classify it as being somewhere in between. Once you get a serious tianeptine habit going (tianeptine sodium) the withdrawal starts to manifest as soon as 4 hours after dosing, so it is definitely fast moving, but the benefit is that the whole thing (acute withdrawal) is over far more quickly than with something like oxycodone (tianeptine sodium sort of feels like oxycodone-light if I had to draw a parallel).

I also have experienced horrific withdrawal from benzo addictions that were unspeakably brutal and did not notice any gabaergic tinge to tianeptine withdrawal.

There is however something a bit different with tianeptine withdrawal (ontop of the opioid withdrawal symptoms), sort of reminiscent of antidepressant withdrawal, akin to tramadol withdrawal perhaps, though a bit different.

Make no mistake, tianeptine withdrawal sucks and can be very acute, but it certainly doesn't compare to the sheer agony of cold turkey heroin withdrawal, or the prolonged seemingly endless hell of acute methadone withdrawal. Those that think tianeptine withdrawal is worse than the withdrawal from things like heroin lack experience with opioids.

 

[beebs76]

I have done a LOT of drugs, and have experienced acute withdrawal from a wide array of opioids (from high dose heavy duty narcotics like methadone, oxycodone, IV heroin, fentanyl, poppy pods, to lighter stuff like tramadol and kratom), and from my extensive experience with tianeptine, I would classify it as being somewhere in between. Once you get a serious tianeptine habit going (tianeptine sodium) the withdrawal starts to manifest as soon as 4 hours after dosing, so it is definitely fast moving, but the benefit is that the whole thing (acute withdrawal) is over far more quickly than with something like oxycodone (tianeptine sodium sort of feels like oxycodone-light if I had to draw a parallel).

I also have experienced horrific withdrawal from benzo addictions that were unspeakably brutal and did not notice any gabaergic tinge to tianeptine withdrawal.

There is however something a bit different with tianeptine withdrawal (ontop of the opioid withdrawal symptoms), sort of reminiscent of antidepressant withdrawal, akin to tramadol withdrawal perhaps, though a bit different.

Make no mistake, tianeptine withdrawal sucks and can be very acute, but it certainly doesn't compare to the sheer agony of cold turkey heroin withdrawal, or the prolonged seemingly endless hell of acute methadone withdrawal. Those that think tianeptine withdrawal is worse than the withdrawal from things like heroin lack experience with opioids.

I hear ya. I take the Sulfate version. I am sure you can withdrawal from it but I have not experienced anything that bad. Then again, I don't ever go above 200 MG when I do do that. I don't really notice much the next day other than feeling a bit "blah." It sounds like the Sodium is a totally different animal. It comes on faster and goes away faster, but has a bigger risk for withdrawal. How much of the Sodium do you take at once? Have you tried the Sulfate? It is a nice lil warm feeling for 6 hours at 100MG +.

 

[negrogesic]

I hear ya. I take the Sulfate version. I am sure you can withdrawal from it but I have not experienced anything that bad. Then again, I don't ever go above 200 MG when I do do that. I don't really notice much the next day other than feeling a bit "blah." It sounds like the Sodium is a totally different animal. It comes on faster and goes away faster, but has a bigger risk for withdrawal. How much of the Sodium do you take at once? Have you tried the Sulfate? It is a nice lil warm feeling for 6 hours at 100MG +.

The sulfate is definitely milder feeling and less potent by weight than tianeptine sodium (which has far higher abuse potential due to its strikingly different pharmacokinetics, specifically far quicker time to peak plasma).

I would dose quite high, usually 500mg each dose (which roughly resembles 60-80mg of oxycodone), and take this dose a few times a day. Sometimes I'd dose over a gram in a single dose. I've used the sulfate plenty of times but wasn't a fan. I've also had a number of other variants, like the ethyl ester, free acid, and the iodo variant.

If I were you, I'd quit while you're ahead, or stick to occasional doses of the sulfate. I don't mess with tianeptine anymore personally, can't control myself with that stuff so I avoid it. If I buy a 5g bag of tianeptine sodium for instance, I'd consume it until it gone (and would probably do the same with the sulfate to be frank).

 

[beebs76]

I hear ya. I guess if you are looking for that Oxy Feeling ya have to go with Sodium and go high. That has to be a bit pricey after awhile... I just use Tianeptine Suflate for a nice little low-grade "buzz." I am afraid to try the Sodium because I think I'd like it too much. Tianeptine Sulfate 100MG with some nicotine Vapes is a ncie lil start to your evening IMO. And then take another 100MG the next morning. That is how I do it.

 

[AlsoTapered]

i concluded that tianeptine is a supergonist. Don't confuse that with meaning 'super potent' but rather that it's interaction with the MOR is greater than that produced by the endogenous opiates.

It's a well studied phenomenon in other classes of medicines but isn't well studied within MORs.

It's POSSIBLE that carfentanil and a few other compounds are also superagonists but only BU72 has been confirmed as such.

That means your body cannot reproduce the effects of high-dose tianeptine. I say 'high dose' because at the doses involved in it's use as an antidepressant aren't sufficient to produce a level of MOR activation that the body cannot reproduce.

Anyone designing an opioid with a view to keeping people using would surely pick a superagonist since treatment with an agonist or partial agonist wouldn't be very successful.

Even before I read all the papers, I had noted people rapidly moving from posts saying 'this stuff is great' to 'this stuff is awful' due to it's severe withdrawal syndrome.

 

[beebs76]

Let me ask you this, do you think Tianeptine can be a threat of overdose like other Opiates? I have seen a lot of differing opinions on that. I am very careful with it and only take 100-200MG at a time on the weekends to cut loose a bit. I have never felt the withdrawal many people talk about, but I take the Sulfate. Anyhow, one time I took 400 MG of the Sulfate and drank a few beers and noticed later that evening when sleeping my breathing was not as intense (more shallow). I get it from a reliable vendor and have even taken drug tests the day after taking it and I have always passed the U.I. It reminds me a lot of Tapentadol and Tramadol.

 

[AlsoTapered]

If you are aware enough to NOTICE changes in respiration, you aren't overdosing.

Case Reports of Fatalities Involving Tianeptine in the United States

Abstract. Tianeptine is a tricyclic anti-depressant that is also known to have opioid receptor activity. We present two fatal cases of tianeptine intoxication i

academic.oup.com

Tianeptince can and has caused fatal overdoses, specifically at high doses and mixed with alcohol.

 

[beebs76]

That is wild. Thanks for sharing. I think the Sodium is much more dangerous for overdose (at high doses) than the Sulfate.

 

[AlsoTapered]

That is wild. Thanks for sharing. I think the Sodium is much more dangerous for overdose (at high doses) than the Sulfate.

I certainly wouldn't trust in that. the MW of the sulfate salt is higher so obviously it's less potent by weight but be it the sodium salt or the sulfate salt, it's the freebase that crosses the blood-brain barrier so the action won't differ.

 

[beebs76]

Hmmm... I took Sulfate for like 12 days in a row, my last dose was 200MG at night, and then I took a few days off and didn't feel much other than slight nausea and a fast heart rate for a day. But I am on Cymbalta so I wonder if that is why I didn't have the side effects some have?