Tianeptine

Summary

Tianeptine, known by its trade names Stablon and Coaxil, represents an unconventional type of antidepressant. Although it is primarily prescribed for its antidepressant properties, it is sometimes taken in high doses recreationally to achieve opioid-like effects. Its mechanism of action is unique and not fully understood, primarily involving the modulation of the brain’s monoaminergic system.
While Tianeptine falls under the classification of tricyclic antidepressants (TCAs), its pharmacological effects set it apart from conventional antidepressants. Unlike typical antidepressants that primarily influence monoaminergic neurotransmitters like serotonin, dopamine, or noradrenaline, Tianeptine is believed to operate on glutamate and glutamatergic mechanisms. This action is thought to enhance the brain’s adaptability to stress and depression. Clinical trials have indicated that Tianeptine is as effective as more commonly used antidepressants such as fluoxetine (an SSRI) and amitriptyline (a TCA). Remarkably, it appears to have fewer side effects and complications than traditional antidepressants.
Beyond its antidepressant qualities, Tianeptine also demonstrates anxiolytic (anxiety-reducing) properties, showing promise in treating panic disorders. Furthermore, it exhibits neuroprotective attributes and has been found to enhance cognition in individuals with depression. The combination of its anxiolytic and mood-enhancing effects, coupled with its potential neuroprotective and cognitive benefits, has led to its popularity as a nootropic.
At recreational doses, Tianeptine users report experiencing effects such as sedation or stimulation, anxiety reduction, increased motivation, and euphoria. Official prescription guidelines recommend taking Tianeptine in 12.5 mg doses thrice daily, with a 3-4 hour gap between doses. However, recreational users consume quantities ranging from 12 to 35 mg more commonly.
It is essential to note that limited information is available regarding the potential toxicity of recreational Tianeptine use. Some users have reported that its opioid-like effects can lead to physical and psychological dependence, akin to traditional opioids like heroin, morphine, or hydrocodone. Therefore, it is strongly advisable to exercise harm-reduction practices when using this substance.

Identifiers

IUPAC name
CAS Number	72797-41-2  30123-17-2 (sodium) 1224690-84-9 (sulfate) 2231739-19-6 (hemioxalate)
PubChem CID	68870
IUPHAR/BPS	7558
ChemSpider	62102
UNII	0T493YFU8O
KEGG	D02575
ChEBI	CHEBI:91749
ChEMBL	ChEMBL1289110
CompTox Dashboard (EPA)	DTXSID7048295
ECHA InfoCard	100.131.750 100.069.844, 100.131.750
Chemical and physical data
Formula	C21H25ClN2O4S
Molar mass	436.95 g·mol−1

Chemistry

Tianeptine, classified as a tricyclic antidepressant due to its molecular structure comprising three cyclic compounds, stands out for its distinct effects and mechanisms compared to other tricyclic antidepressants.
Variants in Sodium and Sulfate Salts
Like many medications, tianeptine can be synthesized in various salt forms to optimize bioavailability, absorption, and overall efficacy. Tianeptine is most commonly encountered in its sodium salt form, as it is available in pharmacies and prescribed by medical professionals. However, the sulfate salt variant has also emerged in the market, particularly on nootropic vendor websites, where it is touted as potentially superior to sodium salt. This superiority is often attributed to its extended half-life and prolonged duration of action.
While no formal scientific research supports the enhanced efficacy of the sulfate form, user testimonials suggest potential advantages, such as increased effectiveness and prolonged duration compared to the sodium salt. It’s crucial to note that the sulfate form is not more potent but is metabolized more slowly by the body, allowing for a once-daily dosing regimen that can be more effective. Users have reported that the sulfate form appears to carry a lower risk of addiction due to its slower metabolism. Furthermore, the sulfate form offers a more gradual experience compared to the sodium form, which achieves its peak antidepressant effect more rapidly and returns to baseline more abruptly.

Pharmacology

In contrast to most prescribed antidepressants, tianeptine appears to exert minimal direct influence on monoamines such as dopamine and serotonin. Although tianeptine does cause a slight elevation in extracellular dopamine levels, the precise mechanism responsible for this release remains unknown.
Experiments conducted on rats have demonstrated that tianeptine does not raise serotonin levels in subjects. Instead, it has been observed to enhance serotonin reuptake, categorizing it as a selective enhancer. This contrasts with the most commonly prescribed antidepressants, selective serotonin reuptake inhibitors (SSRIs). However, tianeptine’s impact on serotonin is likely not a pivotal aspect of its mechanism.
Tianeptine also contributes significantly to enhanced neuroplasticity by modulating glutamate and its receptors, notably by indirectly affecting NMDA receptors. Such enhancements in brain plasticity have been associated with a substantial reduction in symptoms related to stress and depression. More recent research has suggested that tianeptine is also an effective agonist of μ-opioid receptors, which could contribute to its antidepressant and anxiolytic properties.
Additionally, tianeptine finds applications in treating conditions such as irritable bowel syndrome and asthma, aside from its use in managing depressive symptoms.

Subjective effects

Disclaimer: The effects detailed below are sourced from the Subjective Effect Index (SEI), a research compilation based on anecdotal user accounts and personal evaluations by contributors to PsychonautWiki. Therefore, it is advisable to approach these effects with a measure of scepticism.

It is essential to recognize that these effects may not manifest consistently or predictably, with higher doses more likely to induce the full spectrum of products. Moreover, increased amounts carry an elevated risk of adverse outcomes, including addiction, severe harm, or even fatality ☠.

Physical:

1. Stimulation
2. Heightened Physical Euphoria – More substantial euphoria has been reported, particularly at doses near or exceeding 100 mg. These sensations closely resemble those typically associated with opioids.
3. Bronchodilation – Tianeptine’s serotonin reuptake enhancement has been found to counteract bronchoconstriction.
4. Muscle Relaxation
5. Headaches
6. Dizziness
7. Constipation
8. Physical Fatigue

Visual:

1. Internal Hallucination – Users may enter a state of semi-consciousness and hypnagogia during heavy nodding at higher doses, leading to dream-like states and imagery up to level 3. Vaguely defined geometric patterns often accompany this experience.

Cognitive:

1. Heightened Motivation
2. Anxiety Suppression – Tianeptine has effectively mitigated the effects of panic attacks.
3. Cognitive Euphoria – More pronounced euphoria has been reported, especially at doses near or exceeding 100 mg. These sensations closely resemble those of typical opioids.
4. Enhanced Focus – Besides boosting concentration, tianeptine improves short-term memory retention, facilitates quicker learning, and enhances reaction time.
5. Thought Acceleration or Deceleration
6. Rejuvenation
7. Cognitive Fatigue – Though infrequent, some users may experience mental drawbacks, such as impaired thought processes.

Toxicity

The toxicity and potential long-term health consequences of recreational tianeptine use remain unexplored within scientific research, and the exact toxic threshold remains unknown.
Based on anecdotal reports, no adverse health effects appear to be associated with experimenting with the drug individually at low to moderate doses, provided it is used sparingly (though absolute certainty cannot be guaranteed). Before consumption, it is imperative to conduct independent research to confirm the safety of combining two or more substances.
Utilizing harm reduction strategies is strongly advised when engaging with this substance.
Lethal Dosage
The LD50 (lethal dose for 50% of individuals) of tianeptine has not been officially determined; however, it seems to possess a substantial therapeutic index and margin of safety. In a tragic incident in 2007, a 26-year-old individual consumed excessive tianeptine in conjunction with alcohol, resulting in a fatality.[22] Nonetheless, accidental ingestion of a lethal dose is unlikely. To ensure safety while using tianeptine, it is recommended not to exceed 100 mg in a single amount or 300 mg within a day.
Tolerance and Potential for Addiction
The chronic use of tianeptine may be considered mildly addictive and can lead to physical and psychological dependence. In cases of physical dependence, withdrawal symptoms may manifest if one abruptly discontinues use.
Tolerance to many of tianeptine’s effects, including its therapeutic benefits, develops with prolonged usage. Consequently, individuals may need progressively larger doses to achieve the same impact. Subsequently, it takes approximately 3 to 7 days for the tolerance to decrease by half and 1 to 2 weeks to return to baseline (without further consumption). There is a possibility of cross-tolerance between tianeptine, other tricyclic antidepressants, and opioids.
Notably, due to tianeptine’s relatively short duration of effects, some users may feel compelled to engage in frequent redosing. The euphoric potential impact of high doses (exceeding 100 mg) might encourage users to surpass recommended dosages, leading to rapid tolerance escalation and intensified adverse effects. Additionally, tianeptine possesses properties as a μ-opioid agonist, potentially contributing to addiction and withdrawal dynamics reminiscent of opioids.[23] For individuals seeking to discontinue tianeptine, it is advisable to taper off usage rather than abruptly discontinuing it to minimize negative discontinuation symptoms.
Tianeptine withdrawal can manifest with as little as approximately 500 mg per day, and the severity increases proportionately to daily dosage and duration of use. Withdrawal symptoms mirror opioids, including flu-like symptoms, teary eyes, runny nose, dry heaves, and emotional instability. Due to tianeptine generally having milder recreational effects than other opioids, withdrawal from this substance can be notably more challenging than discontinuing a similarly euphoric dose of a traditional opioid.

Legal status

Tianeptine is available by prescription in numerous European, Asian, and South American nations and is marketed under brand names like Stablon and Coaxil.

Here is the regulatory status of Tianeptine in various countries:

1. Canada: Tianeptine is unregulated in Canada, meaning it can be legally possessed without requiring a license or prescription.
2. Germany: Tianeptine is classified as a prescription medicine in Germany in accordance with Anlage 1 AMVV.
3. Russia: Since 2010, tianeptine has been categorized as a Schedule III controlled substance in Russia.
4. Sweden: Tianeptine lacks approval as a prescription medication in Sweden and is consequently treated as a controlled substance.
5. Switzerland: Tianeptine is not controlled under categories A, B, C, or D in Switzerland, suggesting it may be considered legal.
6. United Kingdom: The Psychoactive Substance Act, effective since May 26, 2016, renders the production, supply, or importation of Tianeptine illegal in the United Kingdom.
7. United States: Presently, Tianeptine is not federally regulated in the United States. Nevertheless, many nootropic vendors have discontinued its distribution due to its potential for recreational use and abuse. In March 2018, the Michigan state legislature passed a bill designating tianeptine sodium salt as a Schedule II controlled substance, marking it as the first state to classify it.

FAQ

• What is Tianeptine?
• Tianeptine is a medication primarily prescribed for its antidepressant properties. It is available under brand names such as Stablon and Coaxil.
• How Does Tianeptine Work?
• Tianeptine’s mechanism of action is unique among antidepressants. While it is classified as a tricyclic antidepressant (TCA), it is believed to modulate glutamate and glutamatergic mechanisms, enhancing the brain’s adaptation to stress and depression.
• Is Tianeptine Available Over the Counter?
• The availability of Tianeptine varies by country. In some places, it is available by prescription only, while in others, it is unregulated and can be obtained without a prescription.
• What Are the Common Uses of Tianeptine?
• Tianeptine is primarily prescribed for the treatment of depression. It has also shown promise in treating panic disorders and has potential nootropic (cognitive-enhancing) effects.
• Is Tianeptine Addictive?
• Tianeptine can be mildly addictive, and prolonged use may lead to physical and psychological dependence. Users may develop tolerance, requiring higher doses for the same effect.
• What Are the Potential Side Effects of Tianeptine?
• Common side effects include headache, dizziness, constipation, and physical fatigue. High doses may lead to euphoria and heightened physical joy, similar to opioids.
• Is Tianeptine Safe to Use with Other Substances?
• Combining Tianeptine with other substances can be dangerous, particularly depressants like alcohol or benzodiazepines. Always conduct independent research to ensure the safety of combining substances.
• Is Tianeptine Legal in My Country?
• Tianeptine’s legal status varies from country to country. It may be available by prescription, unregulated, or illegal. Check your country’s regulations to determine its status.
• What Is the Recommended Dosage for Tianeptine?
• The recommended dosage typically starts at 12.5 mg and is taken three times daily. However, recreational users may use higher doses, which can be associated with increased risks.
• Can I Use Tianeptine to Manage My Health Condition?
• Tianeptine should only be used under the guidance and supervision of a qualified healthcare professional. Do not self-prescribe or use it for unapproved conditions.

References

1. **Defrance, R., Marey, C., Kamoun, A. (1988). “Antidepressant and anxiolytic activities of tianeptine: an overview of clinical trials”. Clinical Neuropharmacology. 11 Suppl 2: S74–82. ISSN 0362-5664.
2. **McEwen, B. S., Chattarji, S., Diamond, D. M., Jay, T. M., Reagan, L. P., Svenningsson, P., Fuchs, E. (March 2010). “The neurobiological properties of Tianeptine (Stablon): from monoamine hypothesis to glutamatergic modulation”. Molecular psychiatry. 15 (3): 237–249. doi:10.1038/mp.2009.80. ISSN 1359-4184.
3. **Wagstaff, A. J., Ormrod, D., Spencer, C. M. (2001). “Tianeptine: a review of its use in depressive disorders”. CNS drugs. 15 (3): 231–259. doi:10.2165/00023210-200115030-00006. ISSN 1172-7047.
4. **Schruers, K., Griez, E. (December 2004). “The effects of tianeptine or paroxetine on 35% CO 2 provoked panic in panic disorder”. Journal of Psychopharmacology. 18 (4): 553–558. doi:10.1177/026988110401800413. ISSN 0269-8811.
5. **Plaisant, F., Dommergues, M.-A., Spedding, M., Cecchelli, R., Brillault, J., Kato, G., Muñoz, C., Gressens, P. (May 2003). “Neuroprotective properties of tianeptine: interactions with cytokines”. Neuropharmacology. 44 (6): 801–809. doi:10.1016/s0028-3908(03)00066-2. ISSN 0028-3908.
6. **Klasik, A., Krysta, K., Krupka-Matuszczyk, I. (September 2011). “Effect of tianeptine on cognitive functions in patients with depressive disorders during a 3-month observation”. Psychiatria Danubina. 23 Suppl 1: S18–22. ISSN 0353-5053.
7. **Tianeptine – A Mood Brightening Drug for Depression and Anxiety, 2014.
8. **TIANEPTINE: WHAT IS TIANEPTINE? | https://smartdrugsforthought.com/what-is-tianeptine/.
9. **Tricyclic antidepressants (TCAs).
10. **Brink, C. B., Harvey, B. H., Brand, L. (January 2006). “Tianeptine: a novel atypical antidepressant that may provide new insights into the biomolecular basis of depression”. Recent patents on CNS drug discovery. 1 (1): 29–41. doi:10.2174/157488906775245327. ISSN 1574-8898.
11. **http://www.ceretropic.com/tianeptine-sulfate-powder/.
12. **Gorthaur111 (2015), Tianeptine Sulfate is VASTLY SUPERIOR to Tianeptine Sodium.
13. **Tianeptine sulfate is so great., 2015.
14. **Invernizzi, R., Pozzi, L., Garattini, S., Samanin, R. (March 1992). “Tianeptine increases the extracellular concentrations of dopamine in the nucleus accumbens by a serotonin-independent mechanism”. Neuropharmacology. 31 (3): 221–227. doi:10.1016/0028-3908(92)90171-k. ISSN 0028-3908.
15. **Mennini, T., Mocaer, E., Garattini, S. (November 1987). “Tianeptine, a selective enhancer of serotonin uptake in rat brain”. Naunyn-Schmiedeberg’s Archives of Pharmacology. 336 (5): 478–482. doi:10.1007/BF00169302. ISSN 0028-1298.
16. **Tianeptine ( Stablon ).
17. **Gassaway, M. M., Rives, M.-L., Kruegel, A. C., Javitch, J. A., Sames, D. (15 July 2014). “The atypical antidepressant and neurorestorative agent tianeptine is a μ-opioid receptor agonist”. Translational Psychiatry. 4: e411. doi:10.1038/tp.2014.30. ISSN 2158-3188.
18. **The serotonin reuptake enhancer tianeptine ( Stablon ) prevents asthma attacks.
19. **The Tianeptine Story: Irritable Bowel Syndrome, VelaPharm and Pharmos Corporation.
20. **Michigan’s Legislature has passed a statewide ban on the antidepressant tianeptine sodium. | https://www.usnews.com/news/best-states/michigan/articles/2018-03-21/snyder-to-receive-bill-on-statewide-tianeptine-sodium-ban.