8 replies to this topic

[Puppeteer]

I should be starting a tianeptine trial soon - hopefully tomorrow! I was just looking for some help from someone more capable at deciphering neurology lingo to determine whether I ought to stop taking NAC (600mg BID) while I'm taking tianeptine. I ask because I'm aware they're both glutamergic and I want to make sure I'm not messing with anything important there. Here's an extract about each compound's involvement with glutamate:

NAC

In addition to the effects on oxidative balance, alterations in cysteine levels have also been shown to modulate neuro-transmitter pathways, including glutamate and dopamine (DA; Fig. 1).^23,24 Cysteine assists in the regulation of neuronal intra- and extracellular exchange of glutamate through the cystine–glutamate antiporter. Whereas this antiporter is ubiquitous throughout all cell types, in the brain it is preferentially located on glial cells.²⁵ The dimer, cystine, is taken up by astrocytes and exchanged for glutamate, which is released into the extracellular space. This free glutamate appears to stimulate inhibitory metabotropic glutamate receptors on glutamatergic nerve terminals and thereby reduce the synaptic release of glutamate.²⁶ Given that relation, the amount of cysteine in the system as well as the feedback via GSH production by neurons may directly regulate the amount of glutamate present in the extracellular space. Furthermore, GSH itself has been shown to potentiate brain N-methyl-d-aspartate receptor response to glutamate in rats.^27,28 Changes in the levels of neuronal GSH may not only alter available glutamate levels, but also have direct consequences on glutamatergic function.

Tianeptine
Tianeptine has been shown to inhibit the pathological stress-induced changes in glutamatergic neurotransmission in the hippocampus and amygdala in animal models (57,110). Using a combined approach of repeated stress and electrophysiological recording, Kole and coworkers (110) found that restraint stress for 21 days persistently enhances the NMDA-receptor component of excitatory postsynaptic currents (EPSCs) of the commissural/associational synapses onto CA3 pyramidal neurons. When rats were concomitantly treated with tianeptine, the antidepressant normalizes the stress-induced changes in the amplitude ratio of NMDA receptor to AMPA/kainate receptor-mediated currents, which may contribute to its neuroprotective properties. Moreover, tianeptine appears to facilitate signal transduction at the CA3 commissural associational synapse by altering the phosphorylation state of glutamate receptors as the enhancement of EPSCs could be blocked by the intracellular presence of the kinase inhibitor, staurosporine. In rats, tianeptine inhibited stress-induced re-scaling of the ratio of NMDA receptor- to AMPA/kainate receptor-mediated excitatory postsynaptic currents (110).

It even sounds to me like there may be potential for synergistic action there, but I don't trust my knowledge in this area enough to try any brazen combinations just yet!

Any responses are hugely appreciated; I can't find anything specific to this situation online and ideally I'd like to keep taking NAC but if I can't get a solid opinion either way I'll stop it just in case.

[magniloquentc0unt]

i took tianeptine for 6 months and just recently stopped
im pretty sure i also took some NAC with it, at some point, and nothing bad ever happened
one word of advice, tho: in my experience tianeptine started working better when i stopped taking all other sorts of supplements
its a med with no precise or simple mechanism of action, so imho the less stuff you injest that might screw things up for tianeptine, the better

[fntms]

I agree, it was better in my experience too to limit the other stuff when taking tianeptine.

[Puppeteer]

Ah, fair enough. Can I ask why you guys stopped with it?

I'm currently taking a pretty standard range of supplements, primarily nutritional stuff: B-complex, Vitamin D, standard multivitamin, creatine, as well as 1g lions mane BID. On top of those I take prescribed Lamictal and Valdoxan, and I'm considering supplementing zinc as well. Any thoughts on whether any of those might interfere with tianeptine working?

[magniloquentc0unt]

short version:
too mild

long version:
altough it had no side effects, it was too weak on the energy motivation profile
it had a nice effect at the beginning, as its said anxiolitic and yet stimulant, helped me noticing beauty in the world, colors seemed different
on the other hand i felt it was making me stupider, probably anticholinergic. Some user over at bluelight said that he was in a bad place after a bad MDMA comedown, and he started to take tianeptine.
while on it, he said he did not notice much, but when he stopped, "his life came back to him". I can say that i can relate, even tho not in a 100% complete way. I have felt stupider and dull after a course of fluoxetine and maybe the tianeptine has restored something.

might very well be pure placebo effect and wishful thinking thou

as for the agomelatine and lamotrigine, i dont know. both work in a misterious way and are exactly the sort of substances i mentioned, with a lot of unclear mechanisms of action.
i think you should try tianeptine alone for two months before you can judge in a meaningful way, theres no other way, and any other conclusion would be of no use.
may i ask what are you taking the lamictal for? someone suggested it to me, too...

[Puppeteer]

Thanks for the thorough response.

I have a relatively severe, debilitating case of HPPD. As it's often theoretically attributed to unusual electrical activity in the brain, anticonvulsants are generally a first port of call and in some sufferers have brilliant results. Haven't seen much so far after a month on 200mg, so I'm hoping to start taking a low dose of Keppra - the most often successful AC in HPPD -as well in the future. Perhaps dial back the Lamictal to 50-100mg and throw in 500-1000mg Keppra. I'm not too sure if that's a great idea just yet, I'll have to discuss it with my psych.

Anyhow, HPPD and Cymbalta (SNRI) related issues are why I'm interested in tianeptine. Awesome to hear about that guys experience with it after MDMA as MDMA's what really threw me into the fucking horrible state I'm in now, though it was much worse at the beginning. Whilst researching it I saw that a patent was filed back in 2005 for 'a preparation of tianeptine for the treatment of neurological damage associated with MDMA' (paraphrasing) and that really piqued my interest. I was prescribed Cymbalta by a GP at the start of the year and it was pretty useful for a few months, but it kinda fucked with other symptoms and I can't really tell if some of the side-effects have persisted - it certainly exacerbated the visual stuff and that seems to have stuck. I just didn't have the wherewithal to research things and order them and dose them and shit at the time but I wish I'd gone straight to something like tianeptine, or that the healthcare system were more fucking consistent with what GPs know and are allowed to prescribe so I could've gotten straight on lamotrigine, but anyhow.

I think I'll take tianeptine for as long as my supply allows (about a month currently, but I might be getting some more from a friend) and assess my situation afterward. I'm in a state where I really don't have the luxury to drop everything else just to work out the particular effects of one thing, so I'll just have to hope for the best!

[magniloquentc0unt]

by the way, i did mdma too, while on fluoxetine.
it might have contributed to the stupidity

[Puppeteer]

Oh really? Before my really unpleasant trips I took MDMA once on fluoxetine and nothing really happened, while my friend was rolling hard on the same dose. Later that night when he'd come down though I got really irritable and energetic and had to lay in bed playing video games for hours, but I don't recall experiencing any kind of hangover. Serotonin's a very weird thing!

[magniloquentc0unt]

yeah, there opinions on the topic "rolling on ssri" are divided... some say it just wont work, some say its the same, some say its amplified.
Personally it was the first time i did MDMA and it was just great. Never reached the same extent the 2-3 times i did it again over the next 1.5/2 years