Tianeptine: The Anxiolytic Nootropic

tianeptine-8768651Tianeptine is a tricyclic antidepressant (TCA) that was originally made and marketed by the French company Servier in the early 1980s. Tianeptine is sold in Asia, Europe and Latin America under the brand names of Stablon, Tianeurax, Coaxil and Tatinol. It is important to mention that in the US Tianeptine is not FDA approved.

Despite the fact that Tianeptine has a tricyclic structure, its distinctive pharmacological properties make it a selective serotonin reuptake enhancer (SSRE). SSRE is different to most antidepressant agents (i.e., selective serotonin reuptake inhibitors (SSRI)) as it decreases serotonin levels as opposed to increasing them. Such mechanistic differences have led researchers to revisit the most documented monoamine hypothesis of depression. Briefly, the three best known monoamines are serotonin, dopamine and norepinephrine neurotransmitters. They are all linked with the regulation of motivation and mood.

The monoamine hypothesis suggests that depression symptoms result from reduced levels of these neurotransmitters. For example, deficiencies in serotonin are often associated with depression and anxiety disorders. Therefore, those kinds of disorders can be improved by reversing monoamine deficits. This explains why they are treated with traditional antidepressant medications that restore the neurotransmitter imbalances in the brain.

In contrast, Tianeptine appears to work by altering the levels of serotonin in a completely different way.

“Most importantly, compared to the SSRIs Tianeptine has a better side effect profile.”

This may provide a new safer and improved pharmacological treatment to the standard approaches in the treatment of depression as it is a better tolerated compound than more common antidepressants.

Tianeptine’s clinical efficacy has been successfully shown in the treatment of depression, anxiety, obsessive-compulsive type behaviours stress-related disorders and autistic symptoms. As an atypical nootropic, Tianeptine may improve the user’s cognitive function. Specifically, following the use of Tianeptine improvements in thought clarity, memory, abstract relationships comprehension and learning abilities have been reported. Some other reported benefits include better sleep quality, mood regulation and ability to relax. Furthermore, Tianeptine has been shown to have neuroprotective properties as it prevents pathological changes and glutamate toxicity in the amygdala and hippocampus areas of the brain.

How does Tianeptine work?

Although, Tianeptine has been studied for more than three decades its molecular mechanism of action remains unknown. However, current evidence suggests that by easily crossing the blood-brain barrier (BBB) it quickly starts working in the brain. There are several theories that have attempted to explain the mechanisms through which Tianeptine achieves its effects in humans.


Several scientific studies have concluded that Tianeptine provides its antidepressant effects through central neuroplasticity, some cellular and neurochemical mechanisms. Tianeptine reverses the pathological damage in certain areas of the brain that has been induced by stress.

It actually protects the brain during stressful experiences. Situations of high tension cause the hypothalamus to produce corticotrophin releasing factor (CRF) or corticotrophin releasing hormone (CRH). In turn, it boosts the production of adrenocorticotropic hormone (ACTH) on the anterior pituitary gland, which promotes glucocorticoid release. Unrestricted psychosocial and physical stress causes increased secretion of cortisol from the adrenal glands. That induces pathological changes on hippocampus and lateral amygdala. Changes like can lead to lower mood and clinical depression.

Tianeptine stops and reverses neural damage. It does that while encouraging synaptic plasticity and neuronal health. Long-term use of this compound may even normalize the hypothalamic-pituitary-adrenal (HPA) system. It lowers the stress and basal induced activity of the HPA system and this way helps the user to deal with stressful experiences. Tianeptine also promotes decrease of corticosterone, ACTH, and CRF, further contributing to its effects.


  • Relives stress and social anxiety
  • Improves mood and mental wellbeing
  • Powerful protective agent

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Other possible mechanisms:

Prolonged use of Tianeptine reduces programmed cell death, known as apoptosis, in the hippocampus. It seems to significantly affect the action of glutamate, the core excitatory neurotransmitter in the brain. By preventing overstimulation of glutamate receptors Tianeptine stops the body’s harmful responses to stress. In addition, higher sensitivity of glutamate receptors is the essential principle behind intellect, memory and concentration improvements in the users. In this specific way, Tianeptine is fairly closely related to other well-known nootropics, like Sunifiram, Aniracetam and Noopept.

One of the latest studies on Tianeptine shows that the substance works as an agonist of delta and mu opioid receptors. The latter help develop euphoria in an individual, which may provide a reasonable explanation as to why Tianeptine is effective when it comes to treating anxiety and improving mood. These results have opened up a whole new field of research on this substance.

More recently, animal model was used to demonstrate its anti-inflammatory properties by suppressing microglial activation.

Cognitive enhancement:

A number of studies support the claim that Tianeptine improves learning abilities and memory by preventing apoptosis and enhancement of behaviour against discriminative tasks. It sharpens spatial memory and preserves the hippocampus from unwanted changes. A study performed on animals found that Tianeptine promotes the long-term memory recall.

Another study on 20 patients with prior diagnosis of depression also produced positive results. The subjects have undergone a three-month Tianeptine treatment and have had cognitive function testing performed on them. It indicated a general improvement in attention, learning processes, immediate memory and reaction time. The results of this study shows that Tianeptine the cognition.

Recommended dosage of Tianeptine:

The typically recommended daily dosage of Tianeptine is 12.5 mg taken once per day. Do not exceed the recommended dosage and any increase in dosage should be done carefully following a consultation with your doctor. Tianeptine has high bioavailability.

Side effects of Tianeptine:

If used within the recommended dosage, Tianeptine is unlikely to induce any psychotomimetic side effects. However, the most reported side effects are drowsiness, dry mouth, dizziness, diarrhea, nausea, headache, constipation, fatigue, joint pain and palpitations. You should not use Tianeptine if you:

  • are pregnant or lactating
  • are allergic to Tianeptine
  • have kidney problems
  • take other similar substances, such as tetracyclic antidepressants, monoamine oxidase inhibitors (MAOIs) and SSRIs.


Tianeptine is an atypical antidepressant agent that has a growing body of evidence to become a popular anxiolytic nootropic. Many researchers predict that Tianeptine will be widely used in the treatment for anxiety-related disorders. Therefore, it can be expected to see Tianeptine among the best nootropics for depression. Further, the users of Tianeptine also report some nootropic and cognitive-enhancing properties, such as improved learning ability and memory.