Tianeptine is a drug that has antidepressant and anti-anxiety effects. It has been shown to reduce depression in Parkinson’s disease and has been effective for Asthma as well.

Introduction to Tianeptine

Tianeptine, also known as stablon, is a drug primarily used in the treatment of Major depressive disorder. It has also been used to treat irritable bowel syndrome and asthma.

Tianeptine has antidepressant and anti-anxiety properties (R).

Tianeptine has a variety of effects on the body, including motivation enhancement, anxiety suppression, cognitive euphoria, focus enhancement, rejuvenation, and cognitive fatigue [R, R2].

Tianeptine was discovered and patented by the French society of Medical Research in the 1960’s. Its brand names include Stablon, Coaxil. Tatinol, Tianeurax, and Salymbra.

Tianeptine is available in European, Asian, and South American countries. It is banned in the United Kingdom. It is not medically prescribed by doctors in the United States [R].

Tianeptine has challenged the monoaminergic hypothesis of depression, as well as the proposed monoaminergic mechanisms whereby the action of most known antidepressants was explained (R).

Like almost every drug, however, no one is sure exactly how tianeptine works or helps the conditions listed.  The mechanisms listed are potential mechanisms by which it can help these conditions.

My Experience With Tianeptine

Tianeptine has a noticeably relaxing effect, but it also has a dopaminergic effect and my dopamine levels are very high.  A tiny dose of any dopaminergic drug such as modafinil, amphetamines or selegiline will be too much for me.  Tianeptine is no exception to that.

However, I am the exception.  The fact that tianeptine can increase dopamine function and also be anti-anxiety is very uncommon because, usually, dopamine can increase anxiety.  So tianeptine is a nice and unique mix.

When a client has anxiety and issues with SNPs of their dopamine receptors (DRD2 and DRD3), I will often mention tianeptine.

Health Effects of Tianeptine

1) Tianeptine Improves Depressive Symptoms

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Tianeptine was as effective as several classical antidepressants in patients with major depression, dysthymia or adjustment disorder. Also, extended treatment with tianeptine decreased the incidence of relapse/recurrence of depression (R).

In an open, non-comparative clinical study in patients with Parkinsons’ disease (PD), tianeptine decreased the severity of depression and also improved the quality of life in these patients (R).

In rats, tianeptine helped with drug-induced seizures and learning and memory impairment. This study shows that tianeptine may benefit depressive patients with epilepsy (R).

Tianeptine may have an additional potential for a specific subgroup of depressed patients like the elderly and those with chronic alcoholism due to a relative lack of sedative, anticholinergic and cardiovascular adverse effects (R).

Tianeptine helps depressive symptoms in postmenopausal women and may decrease appetite. However, it does not affect weight long-term and should not be used for obesity treatment (R).

Tianeptine reduces depression by:

  • Modulating the glutamate receptors, including NMDA and AMPA receptors (R, R).
  • Normalizing glutamate levels.  It reversed stress-induced increases of glutamate in the rat basolateral nucleus of the amygdala (R).
  • Potentiating AMPA receptor function in the frontal cortex (via phosphorylation of GluR1 subunits) (R).
  • Activating the Mu-opioid and delta-opioid receptors, which has antidepressive effects (R).
  • Increasing the release of BDNF (R).
  • Enhancing serotonin reuptake (R) – it helps soak up serotonin from outside of the cell, thereby increasing serotonin inside the cells (RR).
  • Enhancing the mesolimbic (pleasure center) release of dopamine and potentiating the dopamine receptors (DRD2 and DRD3 receptors) (RR).
  • Increasing the responsiveness of the α1-adrenergic system (R). A reduction in alpha-1 noradrenergic neurotransmission increases depressive behavior and likely plays a role in depressive illness (R).
  • Increasing norepinephrine (possibly).

2) Tianeptine Lessens Anxiety, Stress, and PTSD and Symptoms From Stress

In elderly depressive patients, a drug regimen of tianeptine or escitalopram improved anxiety symptoms and subjective and objective neurocognitive functions(R).

In panic disorder patients tianeptine appeared to reduce their reaction to panic challenge (R).

In rats, tianeptine increased respiration and prevented morphine-induced respiratory depression (R).

In a multicenter study, Tianeptine (at 37.5mg dosage) was effective in treating Post-traumatic stress disorder (PTSD) patients when compared to the control (R).

In rats with predator-caused posttraumatic stress disorder (PTSD), tianeptine most effectively prevented the effects of psychosocial stress (R).

In rats given tianeptine, extinction learning and memory were increased. This indicates the tianeptine could change learning behaviors in exposure-based therapy (R).

Tianeptine has memory-protective characteristics, as it blocks the adverse effects of stress on hippocampus-dependent learning and memory (R). Tianeptine blocked stress-induced memory errors in two different tasks (R).

In an experiment where maternally deprived rats were subjected to swimming and field tests, tianeptine helped them cope with stress better (decreased the immobility time and increased the swimming time) (R).

In female rats, tianeptine reduced the effect of stress+lipopolysaccharide (LPS) on BDNF levels better than desipramine and fluoxetine (antidepressants) (R).

Tianeptine, along with similar antidepressive drugs, help restore the damage on biomolecules caused by stress (R).

In stressed rats, tianeptine reversed the decrease in catalase activity caused by saline (R).

In mice, tianeptine lowers stress-caused alopecia areata (hair loss) (R).

Tianeptine reduces anxiety by:

  • Inhibiting stress-induced changes in glutamatergic neurotransmission in the hippocampus and amygdala in animal models (R,R).  It indirectly alters glutamate receptor activity, which in turn affect neural plasticity (R).
  • Normalizing glutamate levels.  It reversed stress-induced increases of glutamate in the rat basolateral nucleus of the amygdala (R) and inhibited glial glutamate transporters (R). Tianeptine prevents the stress-induced reorganization of glutamatergic synaptic vesicles in the hippocampus neurons (R).
  • Enhancing serotonin reuptake (R) – it helps soak up serotonin from outside of the cell, thereby increasing serotonin inside the cells (RR).
  • Regulating prefrontal cortical activity and HPA axis activation in male rats (R).
  • Regulating glucocorticoid receptors in areas of the brain affected by stress from maternal separation (in rats) (R).
  • Increased GABA concentration (via GAD65 expression) in the spinal cord (R).
  • Tianeptine activates adenosine A1 receptors, which might help with anxiety (based on zebrafish) (R). This receptor is activated by adenosine and also lowers heart rate.

3) Tianeptine Benefits Memory and Learning

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Patients with Major Depression (N = 164) were randomly assigned to either tianeptine (37.5 mg/d) or escitalopram (an SSRI) for 12 weeks.

After 12 weeks, the tianeptine group showed significant improvement in commission errors, verbal immediate memory, Mini-Mental State Examination, delayed memory, and reasoning ability, whereas the SSRI group improved in delayed memory and reasoning ability but not in the other measures.

The treatment of Major Depression with tianeptine led to more improvements in neurocognitive functions, especially in commission errors and verbal immediate memory, compared with escitalopram. Both drugs improved subjective cognitive impairment of memory and concentration. (R).

It was shown to exert improving effects on learning as well as on working memory and on reference memory in rodents (R) and to exhibit vigilance-enhancing effects in rats (R) and monkeys (R).

A tianeptine hybrid of tacrine and tianeptine was promising in cellular models of Alzheimer’s disease (R).

4) Tianeptine is an Anti-inflammatory

Tianeptine causes the suppression of lipopolysaccharide (LPS)-induced TLR4 expression. It also has anti-inflammatory benefits in microglial cells (R).

Tianeptine sodium salt suppresses TNF-α-induced MMP-9 expression via inhibition of PI3K/Akt-mediated NF-κB activity and may help prevent invasion by cancer cells (R).

5) Tianeptine Combats Pain

Tianeptine has a bunch of mechanisms by which it can relieve pain.

Tianeptine decreases pain by:

  • Activating the Mu-opioid and delta-opioid receptors, which cause pain relief (R).
  • Increasing GABA concentration (via GAD65 expression)  and activating the 5-HT7 receptors in the spinal cord, which reduces neuropathic pain (R).
  • Activating adenosine A1 receptors, which causes pain relief and reduces seizures (R).
  • Through anti-inflammatory effect.
  • Increasing serotonin and norepinephrine levels in the spinal dorsal horn (R).

6) Tianeptine Helps Treat Irritable bowel Syndrome

Serotonin plays an important role in the Enteric Nervous System in the intestinal tract, where it controls intestinal secretions and the movement of digestive material.

Increased Serotonin causes elevated secretions and movement, which contributes to pain, bloating and diarrhea in patients with Irritable Bowel Syndrome (IBS).

Tianeptine decreases serotonergic activity, and thus improves the symptoms associated with IBS and Nonulcer Dyspepsia.

In a multicenter, open-label, randomized controlled study, tianeptine was effective as the standard drug (amitriptyline) for treating IBS-D (Irritable bowel syndrome with diarrhea) patients (R).

7) Tianeptine Reduces Asthma

In an open study with 25,000 asthmatic patients, treatment with tianeptine provoked an abrupt disappearance of asthma attacks (R).

During asthma attacks, catecholamines and free serotonin are found circulating in the blood. Tianeptine decreases free serotonin in the blood.

It does so by enhancing serotonin uptake by platelets and serotonergic axons at the Central Nervous System.

Free serotonin is taken up by lung cells, which induces bronchial contraction (via 5-HT(3) and 5-HT(4) postsynaptic receptors) [R].

Dosage of Tianeptine

The usual dosage is 12mg 3X a day for a norma weight individual, but some people go up to 25mg at a time.

Contraindications of Tianeptine

In depressive patients with bipolar symptoms, tianeptine, and other antidepressive drugs worsened the mean scores of tests used to measure depression (R).

During pregnancy, tianeptine mimics opiates and may cause neonatal abstinence syndrome (R).

Tianeptine increased binge-drinking behaviors in adolescents but decreased overall alcohol consumption in adults (R).

Possible Side Effects and Negatives

Tianeptine’s side-effects are similar to the side-effects of other SSRI’s. These include nausea, constipation, abdominal pain, headaches, dizziness, and changes in dreaming.

Older patients should take a smaller dosage of Tianeptine, as should patients with renal failure.

Dosage does not need to be adjusted in patients with alcoholism or hepatic impairment, or patients on dialysis [R].

Liver Toxicity

Antidepressants, like tianeptine, increased the risk of liver toxicity (R).

Tianeptine decreases emotional memory

Healthy volunteers were randomized to receive a single dose of tianeptine (12.5 mg) or placebo, and subsequently completed a battery of tasks measuring emotional processing, including facial expression recognition, emotional memory, and attentional vigilance, as well as working and verbal memory. Tianeptine-treated subjects were less accurate at identifying facial expressions and showed reduced memory related to emotion and reduced attentional vigilance to positive stimuli (R).

Tianeptine Warnings

Tianeptine should not be taken in dosages of more than 100 mg/day.

Tianeptine may be mildly addictive, causing both physiological and psychological dependence [R].

Tianeptine may cause a euphoric effect, similar to that of opioids. This effect, combined with user tolerance may compel users to take higher doses than required [R].

Synergies and Drug Interactions

  • In mice, tianpetine combined with exercise exerted synergistic effects on the mouse hypothalamic-pituitary-adrenocortical (HPA) axis (R).
  • In mice, tianeptine increased sensitivity to imipramine, another antidepressive (R).
  • In mice, traxoprodil (NMDA antagonist) did not increase the effects of tianeptine (R).
  • Tianeptine does not affect melatonin levels long term in irritable bowel patients (R).

More Details on The Mechanisms by Which Tianeptine Works

  • In rats, tianeptine activates the mTORC1 signaling pathway and increases dendritic outgrowth, spine density, and synaptic proteins through mTORC1 signaling under toxic conditions in rat primary hippocampal neurons (R).
  • It normalizes the stress-induced changes in the amplitude ratio of NMDA receptor to AMPA/kainate receptor-mediated currents, which may contribute to its neuroprotective properties (R). In rats, tianeptine inhibited stress-induced re-scaling of the ratio of NMDA receptor- to AMPA/kainate receptor-mediated excitatory postsynaptic currents (R).
  • Tianeptine and other antidepressants helped reverse most changes in the insulin-like growth factor-1 of the olfactory bulb in animals (R).
  • With constant tianeptine use, there were changes in structure-dependent mitoproteome in the brains of stressed rats (R).
  • Antidepressants, such as tianeptine, may increase neuronal activity by increasing the field potential through preventing the glycine-induced ion current (R).
  • Tianeptine affects NCAM140 expression and CREB phosphorylation to cause an antidepressive effect (R).
  • Tianeptine prevented B27 deprivation-induced decreases in levels of postsynaptic density protein-95, BDNF, and synaptophysin (R).
  • Tianeptine lowered the effects of dexamethasone-caused cell viability and proliferation (R).
  • Tianeptine prevented contraction of the uterine smooth muscle and increased glutathione peroxidase and catalase activities in uteri. In contracting uteri, tianeptine decreases copper-zinc SOD activity (R).
  • Presumably, actions upstream of dopaminergic neurons are involved, such as tonic GABAergic and glycinergic inhibition of dopaminergic perikarya (RR).

Tianeptine on SelfDecode

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24 COMMENTS

  • Dave

    Mike and Cody what do yall mean when you had a bad experience with newmind? They have been great to me so far I am thinking about buying some tianpetine from them but I wanna know what’s so bad about it. Everything else I’ve had from there is great though.

  • Blake

    I agree with you Mike I had a bad experience with newmind. I personally think that Tianeptine is a great alternative for opiates and those seeking to get off of harder substances.

  • Mike

    I’ve experienced the beneficial effects for the last year of use. My main source of negative feelings was the amount of money I was spending on this product which I knew, like most drugs, is a lot cheaper when one doesn’t have to go through middlemen. The other source of negative thoughts was knowing I was now an addict, for the first time in my life. I have an affinity for drugs but until tia, cigarettes were the only drug that got me – and I got rid of them 32 years ago.

    I just went through an intense hallucinatory experience that put me in the hospital for 2 and a half days. The reason was an excessive loss of potassium. Tia sodium, being a sodium, will depress ;potassium so this needs to be monitored if larger quantities of tia are being taken – larger means anything over a gram a day.

    I much appreciate the good information regarding this supplement. It IS a good stimulant, like all opiates are for me. This is not a classic opiate, but close enough.

    Find a good supplier in China and stop going through so much money. I’ve bought from just about everyone over here. Good quality from everyone except a bad experience with New Mind. Rude bastards as well. Avoid New Mind. They make it easy to avoid them so it won’t be difficult.

    Again . . . thanks for the excellent information.

  • Doug

    It actually made me feel blue and melancholy…I was taking the genuine Stablon tablets. Perhaps a different form would be better?

  • Steven

    Tianeptine Sodium and its siblings Sulfate, Free Acid, and even the new tianeptine oxalate have many more than these 7 benefits, which are just the tip of the iceberg, really. The problem isn’t the tianeptine itself, the problem is finding a reliable vendor to buy tianeptine sodium that doesn’t sell it as a chemical for research purpose because those impurities ware hard on your body. I used to get Stablon, but now I only order from Supplements for Work. As good as sodium gets.

  • Mic

    I have read that tianeptine helps to heal ulcers. Is that true? On one, forum, though, I read that it irritated the stomach.

  • Ron

    I would appreciate it if you could clarify re dosage. You recommend 12 mg 3x/day but I am reading that the sulphate (vs. sodium) version is long acting and does not necessarily require the 3x/day split (and your recommended vendor no longer carries the sodium version, btw). So, do you generally recommend that even the sulphate version be split into several times per day ? Thanks for you input!

  • Gary

    I know it’s not recommended but I do not use tianeptine in doses any lower than 200mg. I don’t feel anything unless I use at least this much. My tolerance is off the charts. I have been on SSRIs and SSNRIs for years and use kratom daily. BUT…. at this dosage I great a really pleasant effect and it makes the days I use it wonderful. I only use tianeptine on the weekend, I don’t want it to become a habitual thing for me as it is not cost effective at the dosages that I require. The most I used in one day was 800mg and that was a bit too much so I never go over 600mg in any one given day now.

  • An-Marie

    My experience with Tianeptine sulfate is as follows : neuropathic pain in feet and legs are notably diminished (probably by modulating NMDA-receptors), no positive effect on dopamine, instead my fatigue worsened and motivation went to zero, anxiety, depression and stress worsened. Although I had some good days on Tianeptine, my symptoms all came back and got worse. Except for vivid dreams, I had no bad side effects. I tried 25 mg, 37.5 mg and 50 mg. They all gave me very bad ánd good moments. It’s very unclear to me wether I tried one dosage long enough, or wether I changed the dosage to soon. Is it that you have to keep trying for weeks to notice some lasting results ? What if you’re symtoms worsen, should you stop or continue ?
    A former “practitioner” claimed that my mu-opioid and delta-opioid receptors are worn out, so maybe using tianeptine is making this problem worse in the long term or isn’t able to do its work properly because of this ?

  • Allan

    It mentioned that Tianeptine decreased the ability to pick up positive stimuli, and “reduced positive affective memory and reduced attentional vigilance to positive stimuli,” which seams very similar to acute Tryptophan depletion-an amino acid- and this makes me wonder if taking supplemental Tryptophan while using Tianeptine, might reduce some of the potential negative symptoms of Tianeptine.
    I think it’s important to note that Tianeptine’s working on the u-opioid receptors in the brain, in and of itself, could explain its primary anti-depressant abilities. The opiates are the best-anti-anxiety, and antidepressant found anywhere in nature!
    I spent years of my life addicted to the fruit of the poppy, and I tried everything natural, and medicinal-from amphetamines to barbiturates-and from cannibas-to Mitragyna Speciosa- and it wasn’t until the opiates, that the heart of my pain, anxiety, and depression, were put in check- albeit short-lived, because of the factors of illegality, but more so, the factor of tolerance, which led to ever increasing doses to the point of the unmanageability that these substances create in the life of an addict. I am noting this because I believe it is the fact that Tianeptine tickles the u-opioid receptors, which account to the primary source of anti-depressant actions.
    Of course, there are other things at work in the brain affected by Tianeptine. It doesn’t have the effect of a classic opiate or opioid, as it does not cause oversedation. It actually has a stimulating effect, which is one of the good qualities of this medicine, but tolerance, and the very short half-life of Tianeptine, is one of its biggest problems, as it can lead to an addiction, that, apparently, is very difficult to get past once the person has become addicted!
    The tolerance, and short half life, leads to many users of Tianeptine- those with a predisposition to addictive behavior-increasing the dosages, which is one factor in the use of Tianeptine, by those vulnerable to becoming addicted, that should be taken into very serious consideration before using this substance to deal with their depression!
    This is the same pitfall that the classic opiates present to those that become addicted to them, while trying to medicate their own psychological and emotional pain! I suspect, developing a way to stop the development of tolerance, the brains response to the repeated use of the opiates, would be a major step in battling addiction.

  • Andy

    This study was particularly enlightening: Tianeptine in an experimental medicine model of antidepressant action

    Mainly because most studies showing tianeptine’s efficacy were on rats, but this study done on humans was clearly a negative. Some excerpts…

    Tianeptine-treated subjects were less accurate at identifying facial expressions, though this was not valence specific. The tianeptine group also showed reduced positive affective memory and reduced attentional vigilance to positive stimuli.

    In healthy human volunteers, however, Lechin and colleagues (2006) demonstrated an acute decrease in plasma serotonin and increase in platelet serotonin following a single oral dose of tianeptine, consistent with an effect to enhance serotonin uptake.

    Acute tryptophan depletion has been shown to decrease the recognition of facial expressions of fear in healthy female volunteers and specifically reduce the recognition of happy faces in recovered depressed patients

    Technical limitations of early microdialysis techniques, such as the presence in solution of citalopram, may have elicited some autoreceptor effects to explain this discrepancy. Additional findings such as the lack of effect on the firing rates of serotonergic neurons have cast further doubt on the role of serotonin in tianeptine’s mechanism of action. Of note, tianeptine shows no affinity for known neurotransmitter receptors.

    Such effects may be mediated via modulations of glutamatergic neurotransmission; tianeptine reduced stress-induced amygdalar glutamate efflux in rats and affects signaling cascades such as potentiating AMPA receptors via phosphorylation of the GluA1 subunit. One recent study representative of a diverse literature surrounding tianeptine’s action shows tianeptine to be a µ-opioid receptor agonist, proposing this as the initial molecular target to trigger downstream effects

    End of excerpts – basically, most of tianeptine’s actions are due to downstream effects because of its agonism for the mu-opioid receptor… not exactly a long-term answer if one is trying to treat depression.

  • Joseph Galazin

    I am utterly confused now!! I read a lot of your information about inhibiting MTOR and why and when we should….and how its even linked to depression in one link you provide. But then I stumble across tianeptine where it stimulates mTOR to provide its antidepressant effect. So can you explain why you advocate inhibiting it at times, yet tianeptine, scopolamine and ketamine all activate it, and this seems to be the mechanism behind the rapid antidepressant effects of these subtances!

    Please reply, because I was just about to go hardcore into mtor inhibition to help my depression until I saw this tianeptine post.

    1. Natcha M

      Depression involves a lot more than mTOR (inflammation, dysbiosis, neurotransmitter imbalances, nutrient deficiencies) so simply fixing mTOR isn’t gonna fix the depression. Antidepressant drugs don’t fix depression through targeting mTOR either. ~Team SelfHacked

      1. Joe

        Actually tianeptine ketamine sarcosine and scopolamine to name a few require mtor signaling….

      2. Joe

        Ketamine sarcosine tianeptine and scopolamine to name a few require mtor signaling for their antidepressant response so wouldn’t inhibiting mtor conceivably cause depressive symptoms in some?

  • Emmie

    On reading this is sounded good for my BiPolar friend. Later I saw that it is not a good idea for BiPolar depression. A contradiction ?

  • Beca

    With Phase One methylation defects including SUOX (Yasko test) and CBS, would the sulphate form be contraindicated in this situation? Tian. sounds wonderful otherwise and well matched to symptoms.

  • Mikey

    Would highly recommend looking in to the sulfate version of Tianeptine. Single dosing (25-40mg) in the morning with a steady release throughout the day and for me and many others, sulfate is the only form of Tianeptine that works.

    1. dawn fischer

      I got the recommended product, which is sulfate in 25mg capsules. It’s a powder. In this article Joe suggests 15mg 3x/day. Can’t make that math work out. 2nd day experimenting with this, first time using a Nootropic. I am no stranger to depression, but never going back to lexapro. Hoping with good other practices Tianeptine will be a breakthrough. Would love to hear about other’s experience with how to dose with these 25mg caps, and how it’s working for you.

  • cody

    i have some and it seems to make me angry and irritable? anyone experience this?

  • Rob

    How long did it take for you to notice Tianeptine effects?

    1. Joseph M. Cohen

      30 min

  • Luigi G

    i love tianeptine – it has been the only drug to make such a difference in my life, however, i have an addictive personality so doses have increased. I am having a break from it for now.

    1. dawn fischer

      how much did you use, and for how long. How does taking a break from it feel?

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