Comment · Fri, December 18, 2015 · Ceretropic & Nootropics Depot
Are high dosages of tianeptine harmful?
Original post in this thread
BigYellowLemon · 9 points
I'm depressed and have been using tianeptine very successfully. It makes me a lot more empathetic, happy, and seems to increase my ability to let go and accept (typical opioid agonist). It feels like a much cleaner, brighter version of kratom with no sedation and little cloudiness. Am I doing harm? The only thing I can think of is liver damage, and I haven't noticed much in that area. Do you think using it in large doses (40 - 60 mg x 3 a day) is bad for the brain? If I discontinue, will I have a down-regulation of all its pro-cognitive effects? I've been using it this way for about 9 days, with 2 days with none. Regardless, I'm going to do a small-scale taper for 2 days. TL;DR Is tianeptine in large doses bad for the brain, and is discontinuing it also bad for the brain? Thanks!
What they were answering
somebodybettercomes · 6 points
That's kind of my point - it's a single patient. If tianeptine is genuinely "hard on the liver" it seems like there should be way more than just a handful of users with liver issues. I think it's more accurate to say that a very tiny percentage of people are predisposed to hepatoxicty from tianeptine. I'm not an expert or anything like that but to me that's what the evidence suggests, or lack of evidence. Everything I've read suggests that tianeptine is not particularly toxic in any way.
u/MisterYouAreSoDumb · Ceretropic & Nootropics Depot
In vitro, tianeptine (0.5 mM) inhibited by only 32% the formation of β-oxidation products from [1−14C]palmitic acid by hepatic mitochondria, but inhibited by 71% that from [1−14C]octanoic acid and by 51% that from [1−14C]butyric acid. The activity of the tricarboxylic acid cycle, assessed as the in vitro formation of [14C]CO2 from [1−14C]acetylcoenzyme A was decreased by 51% in the presence of tianeptine (0.5 mM). The inhibition of both β-oxidation and the tricarboxylic acid cycle appeared reversible in mitochondria from mice exposed to tianeptine in vivo but incubated in vitro without tianeptine. In vivo, administration of tianeptine (0.0625 mmol/kg i.p.), decreased by 53 and 58%, respectively, the formation of [14C]CO2 from [1−14C]octanoic acid and [1−14C]butyric acid, but did not significantly decrease that from [1−14C]palmitic acid. After administration of high doses of tianeptine, however, formation of [14C]CO2 from [1−14C]palmitic acid became inhibited as well, transiently after 0.25 mmol/kg and durably (>24 hr) after 0.75 mmol/kg i.p. Hepatic triglycerides were increased 24 hr after administration of 0.75 mmol/kg i.p. of tianeptine, but not after 0.25 mmol/kg i.p. Microvesicular steatosis of the liver was observed in some mice after 0.75 mmol/kg i.p., but not after 0.5 mmol/kg i.p. We conclude that tianeptine inhibits the oxidation of medium- and short-chain fatty acids in mice. Microvesicular steatosis, however, requires very large doses in mice (0.75 mmol/kg i.p., i.e. 600-times the oral dose in humans), and is therefore unlikely to occur in humans.
The issue is that some people have written me saying they have have been taking 1 gram of Tianeptine Sodium a day. I shit you not, A WHOLE GRAM per day. Nobody knows how damaging that is in humans.
Metabolic activation of the new tricyclic antidepressant tianeptine by human liver cytochrome P450
We conclude that tianeptine is activated by human liver cytochrome P450 into a reactive metabolite. This activation is mediated in part by glucocorticoidinducible isoenzymes but not by P450 IID6 (the isoenzyme which oxidizes debrisoquine) nor by P450 IA1 (an isoenzyme inducible by polycyclic aromatic compounds). The predictive value of this study regarding possible idiosyncratic and immunoallergic reactions in humans remains unknown.
It's prudent to warn people of the possibility of Tianeptine being hard on the liver in some cases; especially when we know people are taking idiotic amounts of it. Is it very hard on the liver in normal instances? No, it does not seem to be. Is there any scientific data on how hard it is to humans when taken at a gram a day? No, certainly not. However, the risk should be stated, so that people can be aware of the possibility. People have tried to commit suicide by overdosing on Tianeptine, and failed. So we know it is safer than a lot of things. However, there is the possibility for it being hard on the liver for certain people, or in certain dosages.