41 replies to this topic

[Ricah]

Yea, dopaminergics are much better at neuroprotection & BDNF than serotonergics, but they 'ren't used for that. Also BDNF protects mainly dopaminergic neurons.

I tried many antidepressant till now (iAchE is the only group i haven't tried yet), so believe me, normal solutions  aren't for me.

 

In ur quoted text, according to the latest research tianeptine doesnt have anything to do with serotonin, i.e it's not an SSRE.

http://www.ncbi.nlm....pubmed/10969144

http://www.ncbi.nlm....les/PMC2902200/

 

Fluoxetine long-term can upregulate 5-HT2, but 2c receptor, which is not good for apathy&anhedonia symptoms (activation of -2c receptors leads to inhibition of dopamine&norepinephrine release) and it is strong SSRI anyway, which leads to downregulation of 5-HT1a, 5-HT2a receptors anyway.

What i'm looking for is upregulation of 5-HT1a (autoreceptors and postsynaptics), 5-HT2a receptor and downregulation (and it would be best if it would be antagonist, look lower why) of 5-HT2c.

 

 

 

I'm aware of photosensitizing effect and that's the reason why i'm not taking this in summer

 

There're few more substances, that can do this shit (for example clonazepam, inositol, also rhodiola rosea upregulates 1a receptor, cannabinoids 2a) and talking about other options is for another thread. Also tried some ways to deplete my serotonin levels (for example by BCAA, cyproheptadine) but it does shit.

 

No matter if its agonist or antagonist it will downregulate 5-HT2 receptor. Its weird according to general rule, but this happens, so antagonists are not the solution for 5-HT2 receptors. As i said before, now i'm looking for case reports in bringing back emotions or feeling pleasure to anything by guys, who used high dose of SJW.

 

But thanks anyway for reply, I appreciate that.

Edited by Ricah, 20 June 2016 - 11:03 AM.

[gamesguru]

yes we no longer think tianeptine is predominant SSRE. many other rich, interesting properties. dopamine and opioid to name a few. i heard this first from my grandma, who apparently learned about it from the local radio.

 

some FLY RCs may be 2C selective, we need further testing unfortunately (and for 2A you can find alkaloids or flavonoids):

https://www.uwlax.ed...006/schultz.pdf

Lorcaserin is the most effective 2C antagonist, a pharm, but has nasty sides, including anorexia. i think cyphroheptadine might help too, again tho, dem side effects.

 

what about bacopa, it boosts global serotonin (also 5-ht6 antagonist)... then ginkgo to block 1A, one of the mentioned alks/flavs to block 2A?

the bacopa would downregulate 2C, given time, and 1A and 2A would upregulate.

alternative strategy is to inhibit TPH2, thus reducing global serotonin, and then to put Rikkunshito (5-HT2C antagonist).

[Ricah]

RC are not the most desirable group for me cuz they're not well tested, but of course, if the benefits will be greater than loss, i'd try them

I'm not chemist, not even a scientist or a PhD. I'm just trying to figure out my depression, and this complicated stuff in substances structure building tells me nothing unfortunately. Also the examples they put in article must be hard to get. I'm just some guy who knows something about brain work etc.

Most sources i looked at, tells, that lorcaserin is 5-ht2c agonist and its not beneficial for me (I know it would downregulate anyway, but agonism inhibits release dopamine&norepinephrine, what i'm trying to avoid). Anorexia-kinda-thing for now its not a problem for now for me, because of mirtazapine use & depression i became pretty plump. If there wont be any better alternatives, I'll give it a shot if it is so selective.

Cyproheptadine already tried, but couldn't stand nasty akathisia. For few days i haven't felt any serotonin blockade (for example aggression behavior, less tiredness), only dopamine/histamine blockade (silting, akathisia).
In my country there is memantine available, but its very expensive and unfortunately it is a weak blocker (if i good resemble their Ki is about 500~ + or even higher).

I'm not trying to boost serotonin, in fact, trying to do something opposite (as a SSRI treatment is part of my problem). Serotonin depletion would bring receptors finally to their natural state, but waiting is not the solution, as i'm waiting more than 2 years after fluoxetine treatment now.

As i said, i tried multiple ways to deplete serotonin, i.e. short tryptophan excluding from diet, taurine (as it blocks making new serotonin), piracetam (according to research it lowers serotonin), shilajit, chamomile ordinary (reserach showed that, maybe cuz of reuptake enhancing property), BCAA (3,5g for week and 10g for week, both 4 times per day, i also added tyrosine to exclude dopamine depletion, it blocks tryptohan&tyrosine transport through BBB) etc. Also heard of many other possibilities like AGN-2979, metergoline, corticoseroids, cinnaserin etc, but many of them are out of my league or in my future menu.

Ginkgo is a good idea and want give it a go in future in high dose, but from different reason (some GABA antagonism, as it may be a part of the problem, SSRI indirectly enhances GABA transmission), maybe I'll add ginkgo to SJW, thanks for reminding their 1a sensitization property.
Blocking TPH2 seems like a worth trying idea. But havent found in quick research any inhibitors (of course i'll do more about soon). Do you know any by now maybe?
This Rikkunshito sound like a great idea, but I guess it is really hard to get (cuz of way of getting or price). But i'll do some research soon on my own of course. That's a very valuable information.


Why you hate so much SJW? I think it's an easy solution to my problem. Of course i really appreciate all the alternatives, they may be worth considered if SJW fails or as a addition.


BTW. Till now i found few case reports, but by MDMA users to bring their 'magic' back (they're thinking, that receptors downregulation may be te problem of the tolerance), but it's not very valuable information for me. However, maybe using SJW high dose is not so dangerouse cuz of theirs opinions somehow (like tyramine problems in case of MAO inhibition).

Edited by Ricah, 21 June 2016 - 08:35 AM.

[gamesguru]

i also didnt find a TPH2 inhibitor, except some drug used to treat malaria, hah. reducing serotonin is tricky, one suggestion is to reduce dietary tryptophan, as it already has some difficulty in competing for brain access against other amino acids. take other steps to increase dopamine and acetylcholine, like TH promoters (maybe horny goat weed, idk) and galantamine or huperzine (low dose, cause they have very potent cholinergic effect, also many other interesting, but weaker, effects).

 

as mentioned, Rikkunshito is natural and an antagonist at 5-HT2C. just an fyi, some of those RCs might be on the dark web (i havent looked on there in a while).

i think SJW is promising solution, especially since it promotes BDNF and regeneration at many of the exact regions which MDMA insults. but cheers to cataracts and foggy vision, anyone? SJW even promotes TH and inhibits DBH, but it has side effects, anxiety, withdrawal suicidality, nausea, and now cataracts. It's just a matter of weighing pros and cons against each other.

[sativa]

Kanna might be a good option?
Ferulic acid also, and Albizia julibrissin aka happiness tree.

Re SSRI & BDNF, surely there are safer ways of inducing BDNF! Theanine has BDNF and GDNF properties for example.

Edited by sativa, 21 June 2016 - 07:38 PM.

[gamesguru]

yes i agree SSRI is not necessarily the wisest solution... but one problem here, BDNF is absorbed very locally; between individual neurons there is fierce competition for nearby neurotrophins. SSRI induces BDNF very selectively on serotonergic terminals, which is also the main site for MDMA toxicity.  theanine is less selective, also perhaps less potent... we would have to look on that, maybe there is no research to answer it? there's newer research indicating tea also blocks SERT at 7+ cups daily, and that could plausibly have an SSRI-mimetic effect.

 

curcumin might also not target forebrain serotonin terminals, again we have to look on the research.  or we just run some trials?  curcumin is MAO, so again the serotonin-BDNF duo comes back in (speculatively).  it takes years for the neurons to turnover, and years for the neurotrophins to affect survival. so patience is key.

[Ricah]

i also didnt find a TPH2 inhibitor, except some drug used to treat malaria, hah. reducing serotonin is tricky, one suggestion is to reduce dietary tryptophan, as it already has some difficulty in competing for brain access against other amino acids. take other steps to increase dopamine and acetylcholine, like TH promoters (maybe horny goat weed, idk) and galantamine or huperzine (low dose, cause they have very potent cholinergic effect, also many other interesting, but weaker, effects).

 

as mentioned, Rikkunshito is natural and an antagonist at 5-HT2C. just an fyi, some of those RCs might be on the dark web (i havent looked on there in a while).

i think SJW is promising solution, especially since it promotes BDNF and regeneration at many of the exact regions which MDMA insults. but cheers to cataracts and foggy vision, anyone? SJW even promotes TH and inhibits DBH, but it has side effects, anxiety, withdrawal suicidality, nausea, and now cataracts. It's just a matter of weighing pros and cons against each other.

Maybe in some future research'll find some TPH2 inhibitor. But thanks anyway for the idea. In some forum in my country i gathered plenty of ways to deplete serotonin (but most of them are inaffective or impossible to get substance) but yes, it's very difficult to lower serotonin levels.

Already tried many ways to increase dopamine (dopamine meds like tianeptine, low dose of amisulpride, metylphenidate, selegiline, pirybedyl, bupropione; precursors like L-Tyrosine, avoiding porno&masturbation, using stuff to upregulate receptors like CDP-Choline, forskolin, magnesium, taurine (and many other NMDA antagonists)) but nothing gave me real relief from my symptoms.

Dopamine is a real problem, but cant treat it this way. I believe, that the real problem is serotonin receptor downregulation (as 5-HT1a (autoreceptors and postsynaptics) and 5-HT2a receptors agonism leads to inhibiton of GABA, which inhibits dopamine, downregulation leads to situation, where it's harder to make a response from them).

 

Huperzine is in my future menu, cuz never tried iAchE and heard here and there, that it enhances emotions. Galantamine is bit more interesting for me because of allosteric nicotinic modulation, but never mind.

 

Yeah, I'll definitely get interested in Rikkunshito, it could be great addition to SJW (if there 'rent any bad interactions).

I'm bit a desperate. I even tried tujone to lower GABA (reason? look upper) which is a poison. And I believe, that problems with eyes may occur only with high sun/UV, but dunno.
 

 

 

Kanna might be a good option?
Ferulic acid also, and Albizia julibrissin aka happiness tree.

Re SSRI & BDNF, surely there are safer ways of inducing BDNF! Theanine has BDNF and GDNF properties for example.

 

Kanna upregulates 5-HT2a, so yeah, it may be. But there's a danger for apatic-abulic syndrome (sorry, i don't know if i translated it good to english, hope you understand what i meant) and of course it has many other cons.

For quick research found, both substances you mentioned are good antioxidants. Does it have any other special farmacodynamics properties?

 

 

Sorry for all these questions, but I don't know many herbs and stuff.
 

Edited by Ricah, 22 June 2016 - 08:54 AM.

[sativa]

Here is my topic on ferulic acid:
www.longecity.org/forum/topic/86853-ferulic-acid-a-natural-nmda-antagonist-and-serotonergic-antidepressant

I've tried happiness tree too, its pleasant. 5-HT2C and 1A activity IIRC.

What about reserpine, it's a serotonin VMAT inhibitor IIRC, which depletes serotonin I think?

[Ricah]

I'll read more about ferulic acid soon, thanks for link to your topic.

 

As i can see, happiness tree agonise 5-HT2c, which i want to avoid. Unfortunately this won't be a supplement for me. I don't want to block dopamine in any way as it must be responsible at least for my anhedonia.

 

Reserpine blocks dopamine and norepinephrine also and this really sucks.

 

 

BTW. Still waiting for the guys, who tried high dose of SJW and are still alive :D

[sativa]

It seems kudzu and amentoflavone possess 5-HT2C antagonism.

[gamesguru]

is it an agonist just at the 2A?? the study isn't clear. anyways i think maybe the simplest idea at this point is paying more attention to the 2A than to the 2C, just reducing tryptophan and adding ginkgo.

"Therefore, the involvement of 5-HT 2 serotonergic receptors in the antidepressant-like effect of amentoflavone was evidenced. A role for 5-HT 2 receptors in the action of some antidepressants has been shown (Redrobe and Bourin, 1998 ) although the role of 5-HT 2 receptors on the antidepressant-like effect of amentoflavone has been investigated in vitro where it was shown to have a remarkable affinity for 5-HT 1A and 5-HT 2C (Butterweck et al., 2002 ), but there is no study about the interaction of 5-HT 2 receptor antagonists and amentoflavone in animal models of depression. Although our findings regarding the interaction of amentoflavone with 5-HT 2 receptors seems difficult to explain, taken together, these results suggest that the antidepressant like effect of amentoflavone depends, at least in part, on the interaction with 5-HT 2 receptor and might be mediated by an agonistic activity at the 5-HT 2 receptors. "

 

i thought kudzu was a component in Rikkunshito, or that's mistaken? either way:

"... 5-HT2C antagonism by active components in rikkunshito may lead to the improvement of anorexia."

 

and here's another: Rikkunshito and 5-HT2C receptor antagonist improve cisplatin-induced anorexia via hypothalamic ghrelin interaction.

[sativa]

It's the daidzein in kudzu that has HT2A activity IIRC