Is this cognitive enhancer a paradox to the current paradigm of depression?
A novel tricyclic antidepressant, which is a paradox to the current paradigm of depression. Here I’ll make the case that it’s a Jekyll and Hyde smart drug.
This article is mostly going to focus on decoding what the human studies are saying about Tianeptine and how this squares up with the anecdotal experiences of Biohackers online.
It has +500 results on Pubmed, including 18 human clinical trials in the past 10 years, so it has a decent body of science behind it.
There’s one thing I find interesting about Tianeptine, it defies the generally accepted model of depression. From the authoritative American paper on the subject:
The monoamine hypothesis of depression predicts that the underlying pathophysiologic basis of depression is a depletion in the levels of serotonin, norepinephrine, and/or dopamine in the central nervous system.
Depression: the case for a monoamine deficiency - PubMed
The monoamine hypothesis of depression predicts that the underlying pathophysiologic basis of depression is a depletion…
Probably something you’ve heard before, however, from a 2010 paper out of Rockefeller University, published in Molecular Psychiatry
Depression is a complex, heterogeneous disorder, and the mechanisms underlying its pathogenesis are not that clear and are the subject of intensive investigation using pharmacological and genetic tools and animal models…
From its abstract:
Tianeptine is a clinically used antidepressant that has drawn much attention, because this compound challenges traditional monoaminergic hypotheses of depression.
The neurobiological properties of Tianeptine (Stablon): from monoamine hypothesis to glutamatergic…
Mol Psychiatry. Author manuscript; available in PMC 2010 Sep 1. Published in final edited form as: Tianeptine is a…
I’ve said elsewhere depression is kind of like the ominously inconclusive, blinking check engine light on a car. It’s a vague sign that something is wrong with your neurobiology. The pharmaceutical industry that produces antidepressant drugs is often vilified as this vampire profiting from the suffering of humanity. The development of drugs like Tianeptine is a sign that pharmaceutical science is being done to shatter paradigms and actually help people.
It’s something of a Jekyll and Hyde antidepressant, here are some anecdotes both positive and negative from Tianeptine users:
“Increased clarity of mind (feels clean and pure), It expands my creativity of thinking (I feel that due to the optimism I experience I can dream and my imagination comes alive — much like when I was a kid and something that is lost in depressed anhedonic individuals), The world looks far more appealing and interesting (even blissfull when I am experiencing something of real beauty).”
“…i find tianeptine energizing, i wake up way more easily in the morning and upon dosing i have a nice, happy little burst of energy…”
“I believe that if I can conquer these side effects then this could potentially be a great drug.”
“I still feel a bit mentally slow but I also feel a lingering euphoric state but the real benefit is that I feel a bit more ‘with it’.”
“I started getting opioid withdrawal side effects when I was trying to taper off to stop taking it, like nausea and leg cramps, and a little bit of cold sweating, but it wasn’t too bad, and it only lasted 3–4 days.”
“I have scoured the forums and this extreme tiredness issue does seem to be apparant in some individuals but it’s not overly common. I guess I’m just a bit unlucky in this respect.”
From a 2014 Australian review that analyzed 35 studies:
Specifically, studies suggest that… the SSRE tianeptine… may exert certain improving effects on cognitive function in depression, such as in learning and memory and executive function.
Pharmacological and non-pharmacological interventions to improve cognitive dysfunction and…
The .gov means it's official. Federal government websites often end in .gov or .mil. Before sharing sensitive…
Upon perusing the abstracts of these studies all that I’m seeing is that it improves cognition in depressed people. Nowhere in the scientific literature did I see it recommended or documented that otherwise healthy people can and should take it, as a smart drug, for performance enhancement. The anecdotal reports coming out of the Biohacker community are another story though, one user reported:
“Not only was I able to function normally but, I also won my weekly Texas hold-em game. And those guys are no chumps; so cognatively speaking I was hitting on all cylinders.”
I’ve reached the conclusion that it is a cognitive enhancer, but with a dark side. From one user’s experience:
“In the above mentioned 3 months, he noticed a very,very sharp cognitive increase (that reflected in his programming and grades) , a sharp decrease in anxiety, depression was totally gone, mood was great, social anxiety took a sh2harp decline and life was better than ever… at the end of those 3 months something BIG happened. His anxiety was almost non-existent, his depression the same, BUT his cognitive abilities took a BIG hit, almost instantly, he was much lower than before starting tianeptine (could not reason complex problems,had very much memory problems, verbal fluency was much lower, he was much slower mentally also sleepy during the day…”
Related Rant on Depression
I’ve read a lot of books but without a doubt, the strangest book I ever read was entitled; He Came to Set the Captives Free and it said something radical about depression. I read it about 15 years ago when I was very religious. This non-fiction book is about demonology and this woman’s unbelievable (and likely fake) story about getting deep into the occult. She describes watching human sacrifices and she actually gets married to the devil at one point in the book. She talks about depression and she says basically that we have these scientific models for depression and a lot of times these models are ineffective in treating depression. She concludes that the primary cause of depression is demonic possession resulting from spiritual impurity — which is radically unscientific of course and not very useful if you don’t have an exorcist on speed dial. She describes humans as being protected by spiritual armor and a chink in that armor can be opened up by doing something unhealthy; bad habits, lack of discipline, or by contact with a spiritually toxic environment or cultural artifact. Which is kind of a useful metaphor for Biohacking depression, isn’t it?
If you are Biohacking depression, resist the analysis paralysis of trying to decode the enigma. Attack it on all fronts…
Supplementation and (maybe) pharmaceutical drugs (like Tianeptine)
Don’t focus on a single strategy, a single neurotransmitter mechanism, or a single drug. Your depression is likely a result of a combination of multiple factors; some will show up on a blood test and some will not. In the crazy demonology book, she recommends that by keeping one’s lifestyle, habits, and thoughts disciplined you minimize the risk of demonic possession that is going to result in depression and mental disease.
It’s a totally weird comparison — I know — but this book was so unsettling that it made a real impression on me. If you are dealing with depression don’t be too dogmatic about it; ruthlessly eradicate any impurities or bad habits from your life holistically.
A handful of studies and clinical reviews have established Tianeptine as an option for treating alcoholic withdrawal, from a review analyzing multiple trials:
Tianeptine is effective in the treatment of depression in elderly and post-alcohol-withdrawal patient subgroups. Tianeptine was more effective in reducing psychic anxiety than placebo in patients with major depression or depressed bipolar disorder with or without melancholia.
Tianeptine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic…
Tianeptine is a novel antidepressant agent, both structurally (modified tricyclic) and in terms of its pharmacodynamic…
Although this doesn’t make it a good cure for a hangover, combining it with alcohol is a very bad idea.
From a 2007 Moscow study of Parkinson’s patients:
The efficacy of [Tianeptine] was greater in patients with less marked depressive and motor symptoms, shorter durations of illness, and less marked cognitive impairments.
Coaxil (tianeptine) in the treatment of depression in Parkinson's disease - PubMed
An open, non-comparative clinical study was performed to assess the efficacy and safety of tianeptine (Coaxil) in…
At least a handful of self-experimenters report that it makes dreams very vivid, one self-experimenter reported:
“Amazingly vivid dreams are happening every night but for some reason I’m having a difficult time remembering them except for short segments. Other than increasing the vivid detail of my dreams it has not affected my sleep at all, even when dosed just before bedtime.”
Perhaps it should be considered a lucid dreaming lifehack.
A Long-Term Focus Drug
From one user’s very detailed report:
“It seemed to increase my ability to focus on things but it was over the course of many months, rather than a short period of concentration. A comparison would be to Ritalin working to help you study for 8 hours straight and pass a test the next day, but it wouldn’t necessarily help you complete a website that takes months of writing content with many different sessions.”
Perhaps, you should sprinkle a little Tianeptine powder on the frosted flakes of your one friend that never follows through on their goals and New Year’s Resolutions. Just kidding, that sounds disgusting!
Mechanism of Action
Of this selective serotonin reuptake enhancer (SSRE):
- Modulates the glutamate receptor.
- Boosts the mesolimbic release of dopamine.
- Facilitates the release of BDNF.
- Protects against neuronal remodeling caused by stress.
A 2013 French paper out of the University of Bordeaux, establishes its Ampakinic effect:
The plasticity of excitatory synapses is an essential brain process involved in cognitive functions, and dysfunctions of such adaptations have been linked to psychiatric disorders such as depression… we here report that the cognitive enhancer and antidepressant [tianeptine] favors synaptic plasticity in hippocampal neurons both under basal conditions and after acute stress. Strikingly, tianeptine rapidly reduces the surface diffusion of AMPA receptor…
Regulation of AMPA receptor surface trafficking and synaptic plasticity by a cognitive enhancer and…
H Zhang, 1, 2 L-A Etherington, 3 A-S Hafner, 1, 2 D Belelli, 3 F Coussen, 1, 2 P Delagrange, 4 F Chaouloff, 5 M…
Now, this is NOT saying that Tianeptine sparks neurogenesis in otherwise healthy individuals, what this and other papers are saying is that it restores Neuroplasticity in the depressed and there’s some debate whether it even does that. So if you are a Biohacker trying to hack your learning ability so you can rapidly learn to fly a helicopter, like Trinity in the Matrix — this is not the smart drug you are looking for. Move along.
It was first synthesized by French researchers Antoine Deslandes and Michael Spedding and patented by The French Society of Medical Research.
Pharmaceutical Grade Sources
You don’t need a prescription to try it. It’s not a great value as Stablon in pill form, 60 pills run about $32, which comes out to about $50 for a month’s supply.
You can get COA-verified pharmaceutical-grade Tianeptine in powder form from NootropicSource.com. It’s quite affordable; 5 grams is $110, that’s over 200 doses!
Tianeptine has a plethora of approved medical uses. However, since Tianeptine lacks availability in many countries …
If you don’t want any more nasty-tasting powders in your life Intellimeds in Europe sells Tianeptine capsules which are also 3rd party verified.
Aesthetics and Usage
A recommended dosage of tianeptine is one red micro scoop (12.5mg) up to three times daily.
You might think that Tianeptine salts would just taste like salt, and unfortunately they do not. The taste is quite bad. One Redditor reported:
“As time went on, I came to loathe the taste more and more.”
Powdered Tianeptine, apparently is quite a bit less manageable than most Nootropic powders, from some other Redditors:
“It sticks to the bag it came in, i t sticks to the scale, it sticks to my fingers. Very annoying to dose.”
“Just you wait til it congeals into a solid mass, as it inevitably will.”
“I bought the 1g pouch from powder city, which came with dessicant inside. Probably 20% is stuck on the sides of the pouch”
A liquid tincture of Tianeptine ($30 for 1500 milligrams) may be a better option, while pricier than the powder form.
It has a blood plasma half-life of 2.5 hours, so it may make for a good on-demand performance enhancer when you need to be in the zone for about three hours.
It produces a euphoric happy high lasting a few hours that some compare to MDMA or oxycodone. So maybe a good idea to try if you have an electronic music festival coming up and you don’t want to take the chance on scoring $15 “Blue Dolphins” behind the bathrooms from a shirtless 17-year-old kid wearing furry pants and angel wings.
Anecdotally, it’s synergistic with cannabis and enhances its psychedelic properties.
There’s at least one documented case of fatal intoxication resulting from combining Tianeptine with alcohol. So probably a good idea to stay far away from the silly sauce while on Tianeptine.
Fatal intoxication with tianeptine (Stablon) - PubMed
Tianeptine (Stablon), although structurally similar to tricyclic antidepressants, acts by enhancing the reuptake of…
Unlike a lot of Nootropics, Tianeptine has some addiction risk worth considering. It has been classified by multiple countries as a controlled substance. According to data from the French firm Servier, withdrawals from Tianeptine can be quite severe if it is being used in high dosages frequently.
An abuser on Drugs-forum.com reported:
“50mg every few hours worked great for a few days. Within three weeks I was at 250mg 4 or 5 times a day. Then, upon abrupt cessation, experienced opioid-like [withdrawal] symptoms.”
Take it in the mornings or early afternoons, any later and it’s likely to disturb your sleep.
When compared to similar compounds, tianeptine has significantly fewer side effects with newer (extended release) research chemical versions becoming available as the popularity increases. The most common side effects include dry mouth, insomnia, and headaches… Unlike many other anxiolytic compounds, tianeptine does not cause sedation… In a similar vein, when compared to other intestinal health remedies, tianeptine causes fewer adverse reactions…
Tianeptine Sodium | Dosage, Side Effects, Science & more
You can buy Tianeptine Sodium online from the recommended source at PowderCity.com. Read all about the correct…
Phenylpiracetam — A handful of self-experimenters report that Phenylpiracetam and Tianeptine very nicely complement each other; potentiating and elongating the euphoric effects of Tianeptine.
Phenylpiracetam: The Expensive Linear-Thought-Promoting Racetam
I'm not a doctor, medical professional, or trained therapist. I'm a researcher and pragmatic biohacking practitioner…
5-HTP — According to one self-experimenter: “It has been a WONDERFUL combination for me — I have noticed a significant difference in the effectiveness of tianeptine when combined with 5HTP.”
5-HTP: the Womanly Antidepressant Cofactor that could Kill You!
I'm not a doctor, medical professional, or trained therapist. I'm a researcher and pragmatic biohacking practitioner…
According to a French paper, Tianeptine is potentiated by salicylic acid in significant blood plasma concentration. Some natural sources of salicylic acid are unripe fruits and vegetables such as blackberries, tomatoes, and almonds.
Undesirable drowsiness is mentioned in about 25% of the anecdotal reports. Some people just find it relaxing.
There is a risk of hepatotoxicity, which I think makes Tianeptine an unsustainable antidepressant or performance-enhancing option, from a 2014 review for clinicians:
All antidepressants can induce hepatotoxicity… Liver damage is in most cases idiosyncratic and unpredictable… The antidepressants associated with greater risks of hepatotoxicity are… tianeptine…
The review concludes that:
Although an infrequent event, [Drug-induced liver injury] from antidepressant drugs may be irreversible, and clinicians should be aware of it.
Antidepressant-induced liver injury: a review for clinicians - PubMed
Although an infrequent event, DILI from antidepressant drugs may be irreversible, and clinicians should be aware of it…
A couple of users have reported uncomfortable intermittent heart palpitations.
There’s at least one anecdotal case of moderate use causing a hypertensive crisis resulting in hospitalization.
Conflicts: You don’t want to consume MAO inhibitors within 14 days of taking Tianeptine, some popular MAOIs are Isocarboxazid (Marplan), Phenelzine (Nardil), Selegiline (Emsam), and Tranylcypromine (Parnate).
I don’t think it’s a good option for long-term use by Biohackers for performance enhancement. However, I will go ahead and try Tianeptine because its Nootropic mechanisms are quite different than any of the +100 smart drugs I’ve used and my pharmacological curiosity compels me to hunt down strange molecules to introduce to my neurobiology. The risk-reward tradeoff for what could be a real cognitive blastoff seems pretty reasonable as long as I keep my usage infrequent and the dosage very moderate. See my review of Tianeptine…