Tianeptine regimin before MDxx for serotonin up-regulation?

[2CEECS]

Hi all,

Has anyone tried using Tianeptine in preparation for an MDxx trip? Definitely not a good pre-load choice; I mean at least a week or two of use up until the day before the drop.

It seems to me that this SSRE would up-regulate serotonin, and potentially deliver an enhanced serotonergic rush from a given MDxx. If so, this is clearly useful for several substances in the class, but in particular it could make bk-MDMA a bit more similar to MDMA itself by promoting the serotonergic side of its activity.

The immediate follow-up to this is one that I have less informed intuition about--would such a potentiation also entail an increased risk of serotonergic toxicity from a particular dose of said MDxx? Since I always preload with Selegiline, antioxidants, and 5-HTP, I'm hoping an informed and rare execution of such a strategy could be completely non-toxic...but I'm curious for some thoughts on the toxicity implications as well as effectiveness.

 

[MeDieViL]

It wont work because tianeptine does NOT lower the ammount of serotonin[1].

 

[MeDieViL]

If you want to reverse MDMA tolerance use sint johns wort its proven to upregulate some serotonin receptors and has been used succesfully for this purpose by a few ppl.

 

[2CEECS]

Wow, that's quite a surprising study--it would seem to imply that Tianeptine is serotonergically inactive, which is contrary to a wealth of other information on the net that considers it the only known SSRE.

I know St. John's Wort is a cocktail of chems, but doesn't it primarily have SSRI action? Wouldn't this tend to downregulate serotonin? Perhaps its receptor specificity profile is such that it helps in MDMA tolerance anyway.

 

[MeDieViL]

Wow, that's quite a surprising study--it would seem to imply that Tianeptine is serotonergically inactive, which is contrary to a wealth of other information on the net that considers it the only known SSRE.

I know St. John's Wort is a cocktail of chems, but doesn't it primarily have SSRI action? Wouldn't this tend to downregulate serotonin? Perhaps its receptor specificity profile is such that it helps in MDMA tolerance anyway.

Yeah, the whole SSRE thing is complete bullshit.

It is a very weak SSRI, here's the study showing that it upregulates 5HT1A and 5HT2A.

Pharmacopsychiatry. 1997 Sep;30 Suppl 2:113-6.
Effects of long-term administration of hypericum extracts on the affinity and density of the central serotonergic 5-HT1 A and 5-HT2 A receptors.

Teufel-Mayer R, Gleitz J.

Department of Naturheilkunde, Ulm University, Germany.

Extracts of St. John's wort, Hypericum perforatum L. (Hypericaceae), are used as a phytotherapeutic antidepressant. A number of clinical studies demonstrate that their antidepressive potency is comparable to tricyclic antidepressants (TCA). Although the therapeutic effect of hypericum extracts is well documented, very little is known about the molecular mode of action. As the improvement of the depressive symptoms with both TCA and hypericum extracts only occurs significantly after a lag phase of 10 to 14 days, it is assumed that the medication causes long-term adaptations within the central nervous system. In this context, serotonergic (5-HT) receptors are of special interest. Therefore, we investigated possible alterations in affinity and density of 5-HT1 A and 5-HT2 A receptors caused by long-term treatment of rats with St. John's wort. The brain without cerebellum and brain stem of rats, treated daily for 26 weeks with a commercially available hypericum extract (2700 mg/kg LI 160) were used for membrane preparations. Affinity (KD) and amount (Bmax) of serotonergic receptors were determined by employing receptor binding assays using 3 H-8-OH-DPAT and 3H-Ketanserin as selective radioligands for the 5-HT1 A and the 5-HT2 A receptors, respectively. We found that in hypericum-treated rats the number of both 5-HT1 A and 5-HT2 A receptors were significantly increased by 50% compared to controls, whereas the affinity of both serotonergic receptors remained unaltered. The data suggest an upregulation of 5-HT1 A and 5-HT2 A receptors due to prolonged administration of hypericum extracts. These results are consistent with a modification of the expression levels of serotonergic receptors caused by synthetic antidepressants.

PMID: 9342771 [PubMed - indexed for MEDLINE]

On drugs forum ppl use high doses for 2 weeks, then wait a weak, take MDMA (wich doesnt work for some reason) and take MDMA again a week later, and then the magic is back.

I collected a few experiences in this post:
http://www.bluelight.ru/vb/showpost.php?p=7980092&postcount=3

 

[2CEECS]

That study is also surprising to me, particularly the last sentence--it implies that a traditional SSRI will also upregulate serotonin. However, both my intuition and a quick google search imply that SSRIs indeed decrease serotonin receptor count. In fact, the lag in clinical efficacy is most likely due to 5-HT1 /auto/receptors being downregulated, which allows serotonin /levels/ to rise again, after the initial response of limiting serotonin production.

Given that folks who have actually tried the St. John's Wort method seem to have similar desensitization to MDMA as SSRI-users within the same timespan (a week isn't enough to fully reverse the adaptation), I'm not sure how the study you cite factors into this, but it seems to be counter to both data on other SSRIs and known results of using MDMA after SSRIs.

 

[MeDieViL]

That study is also surprising to me, particularly the last sentence--it implies that a traditional SSRI will also upregulate serotonin. However, both my intuition and a quick google search imply that SSRIs indeed decrease serotonin receptor count. In fact, the lag in clinical efficacy is most likely due to 5-HT1 /auto/receptors being downregulated, which allows serotonin /levels/ to rise again, after the initial response of limiting serotonin production.

Given that folks who have actually tried the St. John's Wort method seem to have similar desensitization to MDMA as SSRI-users within the same timespan (a week isn't enough to fully reverse the adaptation), I'm not sure how the study you cite factors into this, but it seems to be counter to both data on other SSRIs and known results of using MDMA after SSRIs.

What exactly do you mean with that?

And yeah i also tought that SSRI's dont upregulate any serotonin receptors.

 

[2CEECS]

My apologies, I misinterpreted what you said in a rushed reply this morning. After reading the collection of experiences you assembled for the SJW therapy, I see that people are finding it to work...but only after waiting 2 weeks after discontinuing the therapy.

This is quite odd to me. Here's what I know:
1) SSRIs downregulate serotonin, reducing receptor count. MDxx effects are inhibited both during and shortly after a course, and are not found to improve effects above baseline if a dose is taken 2 weeks after stopping the SSRI.
2) Most of SJW's effects are attributed to SSRI action, yet at least one study indicates that SJW can increase serotonin receptor count. There are reports that SJW therapy can improve MDxx response above baseline...but only if there are two weeks without the therapy. Otherwise, an SSRI-like muting of effects is noticed.

These two chunks of info seem to be unintuitive and conflicting. Does anyone have an explanation for the SJW phenomenon in light of the effects of other SSRIs?

Also, has anyone tried the Tianeptine idea? I've seen several other mentions of Tianeptine on BL, including some praise, so I would be surprised if it is completely serotonergically inactive as the rat brain study implies.

FWIW, last night I tried 52mg of what is purported to be crystalline MDA, having used Tianeptine at 3x 12.5mg/day for 2 weeks. I didn't take any Tianeptine the day of. Though this is my first trial of MDA, as well as with this untested substance (only a friends' experience, no lab tests), the experience was a solid ++ and particularly serotonergically rushy. If I had to blindly guess the dose, I would have said 70mg. I don't have any other dosing experience with MDA, but a fair amount with MDMA, bk-MDMA, and MDAI. Effects were consistent with MDA in the form of an extended duration with mild but noticeable visual effects.

 

[avcpl]

M

This is quite odd to me. Here's what I know:
1) SSRIs downregulate serotonin, reducing receptor count.

does it? might the lowered serotonin cause an increase in receptor count to try to maintain homeostasis?

Plus at high doses, SJW acts as an MAOI, which can have receptor count effects too?

found this article today too:
"The time course of fluoxetine-induced supersensitivity of hypothalamic 5-HT2A/2C receptors was examined. Daily injections of fluoxetine (7 or 14 days) significantly increased agonist ([125I]DOI)-labeled high-affinity-state 5-HT2A/2C receptors in the hypothalamus, but not frontal cortex."

http://www.sciencedirect.com/scienc...serid=10&md5=05763f997ecb13f5afb47490a166d5ef

 

[2CEECS]

does it? might the lowered serotonin cause an increase in receptor count to try to maintain homeostasis?

Yes, it would make sense to me that lowered serotonin would increase receptor count--however, SSRIs /raise/ synaptic serotonin!

In any event, there is another complication with SSRIs--the lag in clinical efficacy is caused by a distinctly different period of activity. At first, serotonin levels spike quickly in response to the SSRI, but just as quickly, serotonin autoreceptors (receptors on the transmitting side of the synapse) sense this rise and shut down serotonin production. So, sometimes people note worsened depression, suggestive of a net lowering of serotonin transmission, during this phase. A couple weeks later, the autoreceptors themselves are downregulated, and no longer inhibit serotonin production to the same degree--and the clinically desired effects manifest.

So, it makes a big difference whether we talk about SSRIs administered for 7-14 days (as mentioned in the study), or any period longer than that.

This idea would seem to explain how SJW taken temporarily would be able to increase sensitivity...except, even if taken for only 2 weeks or so, it seems that a subsequent MDxx dose is markedly muted if one doesn't wait at least a week or two after the SJW procedure. That's what doesn't make sense to me.

I'm surprised no one else has tested the Tianeptine idea, because if it does in fact act as an SSRE as the majority of studies claim, it seems to be a far more specialized approach to increasing serotonin receptor count.

 

[avcpl]

yeah, I had the same idea about Tianeptine too, but I won't be trying it because it's not readily available and I assume it isn't for most people (and probably not that cheap either).

I am going to try the SJW for myself next time (two weeks 6g/day followed by two weeks off); that is if my stomach can handle taking that much!