Tianeptine free acid is relatively new to the nootropics marketplace, despite being one of the most common forms of tianeptine. It has all of the same benefits as tianeptine sodium or tianeptine sulfate, with a few major distinctions outlined below.
Tianeptine Free Acid Facts
- The chemical name for Tianeptine Free Acid is 7-[(3-Chloro-6,11-dihydro-6-methyl-5,5-dioxidodibenzo[c,f][1,2]thiazepin-11-yl)amino] heptanoic acid.
- It is not hygroscopic. Unlike sodium salt, this form can be exposed to atmospheric humidity for minutes to hours with no recourse.
- It is absorbed gradually over time. It has a tendency to act as a sustained release with no harsh drop off that many researchers experience with tianeptine sodium salt.
- Many believe that the taste and odor of this substance is a lot less harsh than tianeptine sodium salt.
- It is slightly soluble in water, but very soluble in sodium hydroxide, potassium hydroxide, ethanol and ether.
- It can be converted into tianeptine sodium salt relatively easily.
Tianeptine Free Acid Dosage
Many researchers who try Tianeptine Free Acid for the first time may believe it to be completely inactive. This is because the Tianeptine Free Acid dose can be difficult to understand. While a standard dose for tianeptine sodium is between 12.5 mg and 37.5 mg with a half-life of about 3 hours, and the tianeptine sulfate dose is between 37.5 mg and 112.5 mg with a half-life of about 6 hours, the Tianeptine Free Acid dose starts at around 112.5 mg for most researchers, depending on tolerance, and has a half-life of around 5 hours, although it will take about 40 minutes to take affect.
The difference in dosage is hypothesized to be due to the decreased bioavailability of Tianeptine Free Acid compared to Tianeptine Sodium salt, resulting in the compound passing through the digestive system and being slowly absorbed, with the majority excreted.
The benefits of taking a tianeptine free acid dose instead of a tianeptine sodium salt or sulfate dose can be profound. It provides the gentle sustained release of tianeptine sulfate, but without the hefty price tag. This allows for a more controlled dose and is the perfect form of tianeptine for those who are trying to reduce the amount of tianeptine they intake daily. For those who want a more concentrated dose of tianeptine, you can convert tianeptine free acid into sodium salt with relative ease.
This product is for research purpose only and is not approved by the FDA.
Tianeptine (also known as Stablon and Coaxil) is an atypical antidepressant used to treat major depressive disorder and off-label has been used to treat anxiety, asthma, and irritable bowel syndrome. Despite having the structure of a tricyclic antidepressant, the mechanism with which it exerts its effects is entirely different than the molecules with which it shares its structural backbone. It’s novel antidepressant and anti-anxiety action make it an especially versatile nootropic that has several possible uses.
Early studies of Tianeptine Sodium made the mistake of classifying it has a Selective Serotonin Re-uptake Enhancer (SSRE), due to observations that repeated administration of the drug to rats produced a decrease in free serotonin without any change to serotonin release. In the intervening years since those first studies, this, however, has been proven to be an inaccurate assessment of the drug’s mechanism of action.[i] These results have never been duplicated and, in fact, neither Tianeptine nor its two primary metabolites have shown any direct effect on serotonin release, uptake, or binding in rat models.[ii]
For a long time after the realization that tianeptine did not affect the serotonin system, there was no accepted model of how it exerted its antidepressant and anti-anxiety effects. Despite having an unknown mechanism of action, the interim decades contained several basic scientific and clinical trials that proved the efficacy of tianeptine as a treatment for depressive symptoms. It wasn’t until 2014 when researchers funded by the National Institute of Health finally found what made tianeptine work: it is a full agonist of the human μ-opioid receptor (MOR) and a full agonist of the ϕ-opioid receptor (DOR), although at much lower potency than MOR.i The authors use this result to hypothesize that MOR activation (or possibly the dual activation of MOR and DOR) is the initial molecular event that is responsible for all of the downstream modulations which, in turn, exhibits antidepressant/antianxiety effects.
One example of the downstream effects that MOR activation has is the modulation of glutamatergic neurons in the dentate granule of the hippocampus. These specific neurons have been shown to be involved in stress responses, with their over-activation leading to more severe symptoms of stress.[iii] MOR activation in this region of the brain has been shown to decrease an enzyme which controls the number of NMDA receptors, the primary receptors that respond to glutamate. This has the net effect of decreasing the effectiveness of glutamate in inducing stress. Tianeptine also disinhibits a different subset of glutamatergic neurons in the CA1 region of the hippocampus that have been shown to increase synaptic plasticity in the hippocampus. Strikingly these interactions with the glutamatergic systems of the hippocampus bear striking similarities to how NMDA antagonists, such as ketamine, exert their antidepressant effects.
While it may be alarming to learn Tianeptine acts on the same receptors as opioids, there is no need to fear: it seems to affect the receptor in an inherently different way. For instance, while tianeptine can act as a painkiller and produce reward responses, it does not result in tolerance or withdrawal except in extreme cases of abuse. While it should not be tried at home, there is even limited evidence that when morphine and tianeptine are co-administered, the tianeptine reduces the respiratory depression of the morphine without impairing the pain-killing effects.
Many people who make the decision to use tianeptine as a nootropic supplement report seeing a variety of benefits including better focus, mental and physical energy, and lifting of brain fog. However, there is great variance in the available reports and many mention the occurrence of side effects including headache, dizziness, trouble sleeping, drowsiness, dry mouth, and constipation.
While tianeptine produces significantly fewer cardiovascular, anticholinergic, sedative, and appetite-stimulating effects than other antidepressants, it has been found to possibly be more prone to causing liver damage than other antidepressants. It is worth noting that this research is still contested and not accepted as fact, but it is something to be aware of.
[i] Gassaway MM, Rives ML, Kruegel AC, Javitch JA, Sames D (2014). “The atypical antidepressant and neurorestorative agent tianeptine is a μ-opioid receptor agonist”. Transl Psychiatry.
[ii] McEwen, BS; Chattarji, S; Diamond, DM; Jay, TM; Reagan, LP; Svenningsson, P; Fuchs, E (March 2010). “The neurobiological properties of tianeptine (Stablon): from monoamine hypothesis to glutamatergic modulation”. Molecular Psychiatry.
[iii] Nasca C, Zelli D, Bigio B, et al. Stress dynamically regulates behavior and glutamatergic gene expression in hippocampus by opening a window of epigenetic plasticity. Proceedings of the National Academy of Sciences of the United States of America.