Reminder That Anything People Say On r/Nootropics And Youtube Is Pure Cope

[HTN_Mentalcel]

gonna order it from QSC. But its needed to take with some gaba-t inhibitor, otherwise it stops working fast so i need to take bromantan also

Im looking into vorinostat rn. I need this the most. Impossible to move on with life being so inhibited and suffering from traumas from the past

Im taking seggligine(I think its gaba t its similair to nardil) and sometimes lyrica but lyrica at 200-300mg made me walk funny. I feel like you lose iq when your on it. It has an alcohol type effect.

Please pm if you find a vorinostat source, i cant find one for the life of me. Please bro

 

[russiancelreturns]

Im taking seggligine(I think its gaba t its similair to nardil) and sometimes lyrica but lyrica at 200-300mg made me walk funny. I feel like you lose iq when your on it. It has an alcohol type effect.

Please pm if you find a vorinostat source, i cant find one for the life of me. Please bro

check selleckchem.com

they wanna charge me for 512 jewros with shipping (for 2g)

but ive heard you only need take it in dosages like 50-75mg for few days and your brain should be cured then. Idk tho. 0 info about it on internet

 

[HTN_Mentalcel]

check selleckchem.com

they wanna charge me for 512 jewros with shipping (for 2g)

but ive heard you only need take it in dosages like 50-75mg for few days and your brain should be cured then. Idk tho. 0 info about it on internet

yeah it works by removing old traumatic memories and the anxiety associated with them. It sounds like a miracle and there is a fair amount of testimonies on this.

I even heard 1 pill will do the trick for some people but a few is probably a safer bet.

Its 130 euros for 200mg.

You can read more info about this and other shit on longecity forum. Tell me if you find a cheaper souce that shit is extortion.

 

[russiancelreturns]

yeah it works by removing old traumatic memories and the anxiety associated with them. It sounds like a miracle and there is a fair amount of testimonies on this.

I even heard 1 pill will do the trick for some people but a few is probably a safer bet.

Its 130 euros for 200mg.

You can read more info about this and other shit on longecity forum. Tell me if you find a cheaper souce that shit is extortion.

whats your current stack for mentalceldom and has it helped?

 

[HTN_Mentalcel]

whats your current stack for mentalceldom and has it helped?

1.25/2.5mg subliminally seggligine every other day (3x a week).

Asprin high doses (taken with glycine and vit k2/ eat this through normal food) + Take coffee after a meal if you can tolerate it (aspirin and coffee synthasize for dopamine and aspirin lowers cortisol)

Nicotine patches

L-theanine (mostly cope though, can make you sleepy but its okay with coffee)

High simple carbs like fruit and milk for sugar to lower cortisol (very important as a low carb/ keto will just cause stress and these drugs barely work, the lower carbs you have the more your body runs of cortisol, very bad)

baclofen rarely at high doses for specific shit(It feels better than lyrica for me as you feel like you are more level headed, lyrica makes me dizzy, i dont like it idk)

 

[Deleted member 27550]

Good to see you back bhai. Followed your advice on lyrica 2 months ago, literally saved my social life for my last year at university.

️Bromantane > Lyrica

 

[HTN_Mentalcel]

️Bromantane > Lyrica

my mother looked at one of my packages and knows i ordered drugs. I wanted to get bromatane aswell from swisschems, but that shit is more for careermaxxing isnt it?

 

[russiancelreturns]

1.25/2.5mg subliminally seggligine every other day (3x a week).

Asprin high doses (taken with glycine and vit k2/ eat this through normal food) + Take coffee after a meal if you can tolerate it (aspirin and coffee synthasize for dopamine and aspirin lowers cortisol)

Nicotine patches

L-theanine (mostly cope though, can make you sleepy but its okay with coffee)

High simple carbs like fruit and milk for sugar to lower cortisol (very important as a low carb/ keto will just cause stress and these drugs barely work, the lower carbs you have the more your body runs of cortisol, very bad)

baclofen rarely at high doses for specific shit(It feels better than lyrica for me as you feel like you are more level headed, lyrica makes me dizzy, i dont like it idk)

raypeater I see

 

[russiancelreturns]

my mother looked at one of my packages and knows i ordered drugs. I wanted to get bromatane aswell from swisschems, but that shit is more for careermaxxing isnt it?

I plan to keep drugs at Wolt's bag

 

[HTN_Mentalcel]

@IndraBC whats funny

 

[Deleted member 27550]

@IndraBC whats funny

Nothin

 

[HTN_Mentalcel]

Nothin

have you been using long term and it helped both socially and career wise(concentration)

 

[onlyhereforthehair]

yeah it works by removing old traumatic memories and the anxiety associated with them. It sounds like a miracle and there is a fair amount of testimonies on this.

I even heard 1 pill will do the trick for some people but a few is probably a safer bet.

Its 130 euros for 200mg.

You can read more info about this and other shit on longecity forum. Tell me if you find a cheaper souce that shit is extortion.

which one does that? you guys mentioned a few in the post.
Do you mean vorinostat for healing brain and removing traumatic memory anxiety?

My brain cant function since 2014. and my dr only recommended sleep, vegies and sports

 

[HTN_Mentalcel]

which one does that? you guys mentioned a few in the post.
Do you mean vorinostat for healing brain and removing traumatic memory anxiety?

My brain cant function since 2014. and my dr only recommended sleep, vegies and sports

Vorinostat - Brain Health

Page 1 of 19 - Vorinostat - posted in Brain Health: Hey folks, To go along with the HDAC inhibition discussion thread, Ill be organizing a vorinostat group buy. Its main use is fear extinction and long-term memory enhancement. HDAC inhibition has shown to be able to give people child-like...

www.longecity.org

 

[russiancelreturns]

@HTN_Mentalcel check https://lclabs.com/products/v-8477

 

[HTN_Mentalcel]

@HTN_Mentalcel check https://lclabs.com/products/v-8477

Now I need to deliver this without my family finding out

 

[russiancelreturns]

I think it was $90. With the usual session being around 50mg (for fear extinction), and most people needing max. 5 sessions to experience almost full fear extinction it was a very good deal.

how much vorinostat should I order in your opinion? If you claim the standard dose is 50mg and most people need max 5 sessions. then 1g should be more than ideal?

 

[Cope]

@HTN_Mentalcel check https://lclabs.com/products/v-8477

I feel that would be a hard site to order from, you have to LARP as a research institute. SelleckChem seems more lenient in that regard.

 

[W0KESTMOTHF]

If you can drive to lithuania they dont check prescriptions.

Wym they don't check prescriptions? Like u can just go to a pharma store and buy it? If so it's lifefuel (I'm Lithuanian)

 

[HTN_Mentalcel]

Wym they don't check prescriptions? Like u can just go to a pharma store and buy it? If so it's lifefuel (I'm Lithuanian)

@Tai Lung got accutane without prescription and just said he left it at home jfl

 

[W0KESTMOTHF]

@Tai Lung got accutane without prescription and just said he left it at home jfl

Btw bro do u think Selegiline + Lyrica is a good combo? I know nardil + Lyrica is god tier but it's hard to source nardil, I'm hoping selegiline can at least be partially as good

 

[HTN_Mentalcel]

Btw bro do u think Selegiline + Lyrica is a good combo? I know nardil + Lyrica is god tier but it's hard to source nardil, I'm hoping selegiline can at least be partially as good

That's the stack I've been running, I got it from bgpharma, segligine Is a god substance for general life but I don't really like lyrica it makes you low inhib but I feel like I lose iq and just reduces anxiety but ultimately you are still an autist.

Look into baclofen it much better imo.

When running these drugs eat a lot of simple carbs btw or you won't get the low cortisol effects

 

[W0KESTMOTHF]

That's the stack I've been running, I got it from bgpharma, segligine Is a god substance for general life but I don't really like lyrica it makes you low inhib but I feel like I lose iq and just reduces anxiety but ultimately you are still an autist.

Look into baclofen it much better imo.

When running these drugs eat a lot of simple carbs btw or you won't get the low cortisol effects

How much selegiline are you dosing?

 

[HTN_Mentalcel]

How much selegiline are you dosing?

2.5 subliginally every other day. oral is cope its 4x less effective.

 

[W0KESTMOTHF]

@HTN_Mentalcel any noticeable changes after starting selegiline?

 

[Dyorotic]

Just my two cents

Vorinostat is probably the most speculative drug ever discussed. I have read some decent studies suggesting it has potential to abolish fear but I have yet to see any tangible effects to suggest that and I have pretty severe OCD.

The difference between phenelzine and tranylcypromine is not as significant as people make it out to be. Phenelzine is way more sedating and is more anxiolytic than tranylcypromine but at the end of the day they're both inhibiting monoamine oxidase. Parnate is easier to procure anyway.

Please don't use memegabalin unless you love being a sedated dumb niggercattle. Basically loses any amount of anxiolysis after the first couple of dosages. If you do want to use it daily augment it with donepezil because it blocks the release of acetylcholine.

Bromantane is a complete fucking meme

Cerebrolysin causes hairloss and is inferior to P21.

 

[Dyorotic]

Oh and for anyone that wants to buy Vorinostat it's incredibly easy to get. Go on madeinchina, find a reputable seller, buy the MOQ and then send a sample to Janoshik.

 

[Cope]

Vorinostat is probably the most speculative drug ever discussed. I have read some decent studies suggesting it has potential to abolish fear but I have yet to see any tangible effects to suggest that and I have pretty severe OCD.

My personal experience and the experience of many others would suggest that it does help significantly with anxiety-related conditions. There are anecdotals posted here by users like our admin @Alexanderr and on other sites stating that it was life-changing. Vorinostat is much more nuanced than just the fact that it abolishes fear. The fact that it alters gene expression through the targeting of specific HDAC classes is where the novel aspect of it comes from. You’re obviously not going to find much evidence related to studies lol, no human blind study related to mental benefits has been conducted.

The difference between phenelzine and tranylcypromine is not as significant as people make it out to be. Phenelzine is way more sedating and is more anxiolytic than tranylcypromine but at the end of the day they're both inhibiting monoamine oxidase. Parnate is easier to procure anyway.

Nardil’s inhibition of GABA-transaminase is a significant distinction. Arguably more anxiolytic than benzos without the risk of building tolerance or going through withdrawals due to the lack of downregulation. Both are just as easy to procure if you live in the states.

Please don't use memegabalin unless you love being a sedated dumb niggercattle. Basically loses any amount of anxiolysis after the first couple of dosages. If you do want to use it daily augment it with donepezil because it blocks the release of acetylcholine.

Everyone who says this has never taken prescription Lyrica and only the curry garbage found on the clearnet. Anyone getting it from a pharmacy knows the difference. I always get an anxiolytic effect from it every single time I take it even after consistently taking it for 2.5 years and zero cognitive impairment cuz I don’t abuse it.

Bromantane is a complete fucking meme

It’s nothing compared to Vorinostat and Nardil/Parnate but not useless.

Cerebrolysin causes hairloss and is inferior to P21.

There is way more research on Cerebrolysin and more of a proven track record. Also P21 is very expensive and harder to source.

 

[Dyorotic]

My personal experience and the experience of many others would suggest that it does help significantly with anxiety-related conditions

Probably placebo. I and @androgenic have used Vorinostat extensively & have discussed it at length. We both haven't noticed much at all. My verbal fluency is way way up though and I've noticed it helps immensely with language learning. I don't see it doing absolutely anything with infrequent dosing. I was using it daily for a while but I stopped because it wasn't doing anything for my OCD which I honestly thought it would have abolished when utilized in conjunction with ERP.

Vorinostat has a tiny half life and doesn't enter the brain (comparatively). Someone needs to synthesize Crebinostat and I'd literally spend every last cent I had on it. Panobinostat is much better in basically every respect. Longer half life, higher bioavailability and it actually crosses the BBB.

and on other sites stating that it was life-changing

Yes I've read the entire thread on longecity. Results seem meh.

You’re obviously not going to find much evidence related to studies lol

Humans sure. I've read multiple rat studies and a fair few speculative articles in fear extinction.

Nardil’s inhibition of GABA-transaminase is a significant distinction

Anything GABA related can never be sustained. Everyone who has ever tried to manipulate anything regarding the GABA system eventually comes to the conclusion that a poop-out is a given. It's the one system that will literally do everything to maintain homeostasis. Baclofen is actually an outlier in this regard because GABAb receptor density bounces back very quickly and seems to be quite formidable when agonized for long periods of time. I've used baclofen pretty successfully and sustained it for a while, I only quit because the next-day sedation was too overwhelming. It's provided the most anxiolysis out of any GABAergic I've used and it was intensely antidepressant.

Anyway, phenelzine's antianxiety effect wears off, I've read/heard multiple reports to substantiate such a claim. I don't care if you still feel it, that isn't evidence that the effect wanes over time for most people. Parnate is leagues better in my opinion. It's better tolerated and doesn't seem to cause as many adverse side effects as Nardil.

Everyone who says this has never taken prescription Lyrica and only the curry garbage found on the clearnet

The fact that you're still using this argument is laughable. I've used Pfizer pregab and I've used curry slop, absolutely no tangible difference, in fact, I had 1kg of pure Pregabalin that tested at 99% purity at one point. Again, no difference.

VGCC agonism poops out violently. Pregabalin isn't sustainable. Hundreds of reports will alude to the same thing. Pfizer sedated me just as much as the curry crap did. It doesn't feel good after the first couple days.

Using pregabalin sparingly is probably the most effective way to abolish anxiety though.

It’s nothing compared to Vorinostat and Nardil/Parnate but not useless.

Nah it's dogshit. Poops out like everything dopaminergic.

There is way more research on Cerebrolysin and more of a proven track record. Also P21 is very expensive and harder to source.

P21 is literally the peptide in Cerebrolysin that is primarily responsible for the increase in BDNF expression. It's just synthetic and the fact that it's isolated means you're not running the risk of hairloss and what not when using Cerebrolysin.

Not hard to source at all btw. Not knowing Tracy in 2024 is absolutely wild

The only thing that ever worked for me was Clomipramine and lamotrigine augmented by donepezil. But I dropped all of that and just started thugging it out

getting off psychmeds is probably the best decision I've ever made. If I can source panobinostat I'll definitely get on it.

 

[Cope]

Probably placebo. I and @androgenic have used Vorinostat extensively & have discussed it at length. We both haven't noticed much at all. My verbal fluency is way way up though and I've noticed it helps immensely with language learning. I don't see it doing absolutely anything with infrequent dosing. I was using it daily for a while but I stopped because it wasn't doing anything for my OCD which I honestly thought it would have abolished when utilized in conjunction with ERP.

Vorinostat has a tiny half life and doesn't enter the brain (comparatively). Someone needs to synthesize Crebinostat and I'd literally spend every last cent I had on it. Panobinostat is much better in basically every respect. Longer half life, higher bioavailability and it actually crosses the BBB.

I thought @androgenic had a good response? He made an entire thread on it. Didn't know you took it yourself, you didn't make that clear in your post.

I was actually looking into Panobinostat. Do you have info regarding it crossing the BBB better than Vorinostat? I couldn't find anything on that topic. Might be worth purchasing since it's significantly less expensive than Creb.

Anything GABA related can never be sustained. Everyone who has ever tried to manipulate anything regarding the GABA system eventually comes to the conclusion that a poop-out is a given. It's the one system that will literally do everything to maintain homeostasis. Baclofen is actually an outlier in this regard because GABAb receptor density bounces back very quickly and seems to be quite formidable when agonized for long periods of time. I've used baclofen pretty successfully and sustained it for a while, I only quit because the next-day sedation was too overwhelming. It's provided the most anxiolysis out of any GABAergic I've used and it was intensely antidepressant.

You're grossly uninformed on this but that's ok. Nardil's effect on GABA-tramsaminase works independently from the synthesis of GABA as the increase in GABA levels is based on levels of Vitamin B6. This works completely different from typical GABA receptor agonists since they decrease GABA by increasing receptor sensitivity. Downregulation occurs with reoccurring use of said agent and you’re left with less GABA due to the Glutamatergic system overcompensating as a result. That is very different from Nardil's MoA which works to increase GABA by attempting to balance the GABAergic-Glutamatergic system.

Baclofen only takes a while to build a tolerance to because of its short half-life. The GABAergic system is less likely to take adaptative measures as a result. GABA-B receptor agonists are theoretically more forgiving than GABA-As, but this difference is negligible if the system is under long-term manipulation.

Anyway, phenelzine's antianxiety effect wears off, I've read/heard multiple reports to substantiate such a claim. I don't care if you still feel it, that isn't evidence that the effect wanes over time for most people. Parnate is leagues better in my opinion. It's better tolerated and doesn't seem to cause as many adverse side effects as Nardil.

Phenelzine's anxiolytic effect does lessen, but for the vast majority of users the effect sustains. If corrective measures are taken, the GABAergic effect can be increased.

Why are you trying to argue so adamantly that Parnate is better lol? It's objectively worse than Nardil for those who suffer with anxiety. Their side effect profile is marginally the same, you're going to go thru them initially regardless of either one you take.

The fact that you're still using this argument is laughable. I've used Pfizer pregab and I've used curry slop, absolutely no tangible difference, in fact, I had 1kg of pure Pregabalin that tested at 99% purity at one point. Again, no difference.

Yes, I have also taken Pfizer Pregab from the clearnet and it significantly different than what it is from the pharmacy. No tangible difference for you, but for every responder there is.

VGCC agonism poops out violently. Pregabalin isn't sustainable. Hundreds of reports will alude to the same thing. Pfizer sedated me just as much as the curry crap did. It doesn't feel good after the first couple days.

Not sustainable yet I continue to take it daily with zero issues. Please cite the hundreds of reports for me, you literally just say shit lol. Gabapentin poops out violently, Lyrica is way more consistent. The current brand I'm taking is not at all sedating and actually gives me energy. Your argument does not make sense at all pharmacologically.

Nah it's dogshit. Poops out like everything dopaminergic.

Learn to manipulate the dopaminergic system better.

P21 is literally the peptide in Cerebrolysin that is primarily responsible for the increase in BDNF expression. It's just synthetic and the fact that it's isolated means you're not running the risk of hairloss and what not when using Cerebrolysin.

P21 is a man-made counterpart of CNTF. Like you said its synthetic, therefore not actually found in Cerebro.

Not knowing Tracy in 2024 is absolutely wild

I literally haven't tried sourcing it myself lol

The only thing that ever worked for me was Clomipramine and lamotrigine augmented by donepezil. But I dropped all of that and just started thugging it out

getting off psychmeds is probably the best decision I've ever made.

I did the same. Only taking Lyrica which I have zero downsides from.

If I can source panobinostat I'll definitely get on it.

https://www.selleckchem.com/products/LBH-589.html

 

[Dyorotic]

I thought @

@androgenic had a good response? He made an entire thread on it. Didn't know you took it yourself, you didn't make that clear in your post.

Yeah he thought he did at the start but has since changed his mind.

Didn't know you took it yourself, you didn't make that clear in your post.

Huh I've posted in this thread before. Bought it ages ago

I was actually looking into Panobinostat. Do you have info regarding it crossing the BBB better than Vorinostat?

I was looking into it a while ago. Just look it up. It isn't like Crebinostat tier but the BBB penetration is way higher than Vorinostat

You're grossly uninformed on this but that's ok

What are you on about? I didn't even mention GABA-T. I just said that EVERYTHING that touches GABA in any way imaginble will cause adaptive changes and inevitable downregulation/desenistization. GABAergics are gross and should be avoided entirely if you like your sanity. Pregabalin clears all of them.

Baclofen only takes a while to build a tolerance to because of its short half-life. The GABAergic system is less likely to take adaptative measures as a result. GABA-B receptor agonists are theoretically more forgiving than GABA-As, but this difference is negligible if the system is under long-term manipulation.

There are structural differences between GABAb and GABAa. BPC157, for example, has been shown to reverse tolerance on GABAb but does nothing for GABAa. Tolerance to baclofen is astoundingly low and I haven't seen many anecdotes of people having to increase dosage over time. But yeah it's just like anything GABA-related.

Downregulation occurs with reoccurring use of said agent and you’re left with less GABA due to the Glutamatergic system overcompensating as a result

Why are you trying to school me on something I'm quite understanding of?

Inhibiting GABA-tramsaminase increases GABA's ability to inhibit action potential (well not literally but it'll increase the amount of GABA circulating in the brain), thus causing adaptive changes to the receptor(s) over time. Everything you proceeded to write has absolutely no bearing on whether or not the anxiolytic effect will wane, because it will. You're increasing GABA transmission, plain and simple. Just because it works uniquely to other gabaergic agents (receptor agonists, positive allosteric modulators & GAT-1 inhibitors) doesn't mean it won't invariably decrease the receptors responsiveness to GABA and cause an overcompensation of glutamate transmission (which might not be that bad because with GABA-T inhibition you're at least closer to homeostasis than using benzodiazepines).

So sure, GABA-tramsaminsae inhibition won't lessen the amount of GABA as an adaptive change but it'll cause tachyphylaxis just like any other substance. Increasing GABA via GABA-T inhibition = ↓ GABAa/b receptor sensitvity, increasing GABA transmission via allosteric modulation = ↓ GABAb/a sensitivity + a skewed GABA/glutmate profile. There isn't a fundamental difference here other than the fact that with phenelzine at least the glutamate/GABA ratio isn't violently skewed towards glutamate dominance, which is obviously optimal because it'll make withdrawals infinitely more tolerable.

School me because I seem to be missing something apparently. Interestingly Lamotrigine actually seems to decrease GABA transmission slightly, which just seems odd to me.

Phenelzine's anxiolytic effect does lessen, but for the vast majority of users the effect sustains. If corrective measures are taken, the GABAergic effect can be increased.

Can you give me an example? You can only augment so many times until your augmentation needs augmentation. Psych meds are a complete fucking joke.

Yes, I have also taken Pfizer Pregab from the clearnet and it significantly different than what it is from the pharmacy. No tangible difference for you, but for every responder there is.

Each to their own I suppose. I just don't like pregabalin ig.

Learn to manipulate the dopaminergic system better.

Brother I've been doing this for years. Ironically normalising dopaminergic transmission with aripiprazole gave me better results than using literal meth tbh.

P21 is a man-made counterpart of CNTF. Like you said its synthetic, therefore not actually found in Cerebro.

I concede

I did the same. Only taking Lyrica which I have zero downsides from.

Fair enough. If you can sustain it props to you. I can't ejaculate or work out on pregab so I had to drop it. Plus I've got way to much of an addictive personaility and it made me sleep for half the day.

https://www.selleckchem.com/products/LBH-589.html

I found some on madeinchina and it's from the source I usually buy my raws from. If I get a batch I can send it to Janoshik for HPLC and I'd definitley be down to send you as much as you need for free. Lmk

It'd be pisscheap just like vstat most likely

 

[Dyorotic]

@Cope I don't know if you've seen these studies but they're incredibly interesting, especially for those using HDAC inhibitors.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3717553/

The focus of the electrophysiological portion of the present study was to assess the control of ethanol withdrawal-induced GABA hyposensitivity by HDAC by incubating the slices with HDACi. We observed that inhibition of HDACs abolished the ethanol withdrawal-induced changes in GABA sensitivity of pDAergic VTA neurons in the VTA. It seems plausible that decreases in histone acetylation in VTA induced by upregulation of HDAC2 produces the adaptive changes in the GABA-A receptors, accounting for the GABA hyposensitivity of pDAergic neurons that we observed during ethanol withdrawal.

The ability of HDACi to reverse changes in GABA sensitivity observed in VTA neurons from ethanol-treated mice in withdrawal suggests a change in HDAC activity that is induced by repeated ethanol treatment. We observed that HDAC2 levels were significantly elevated in the ethanol-treated mice at a time equivalent to the time period during which recordings would have been made. We do not know whether other HDAC isoforms were similarly increased during withdrawal after repeated ethanol treatment. Correlated with the HDAC2 increase was a complementary decrease in histone H3-K9 acetylation and expression of GABA (A-α1) R subunit in the VTA; although there may have been changes in other HDAC isoforms, the overall effect of withdrawal after repeated ethanol was to produce a significant decrease in histone H3 acetylation.

Neuroadaptational changes in the histone acetylation and HDAC activity in the amygdala induced during withdrawal after chronic ethanol have been reported to be reversed or prevented by TSA. The few studies performed with respect to HDAC-induced histone deacetylation in response to alcohol administration have focused on the forebrain (Pandey et al, 2008; Moonat et al, 2013; Sakharkar et al, 2012). In particular, changes in histone acetylation associated with drug abuse have centered on the amygdala (Pandey et al, 2008; Sakharkar et al, 2012) and the NAc (Renthal and Nestler, 2009b). One group has observed increases in acetylated histone H3 protein in midbrain during a single withdrawal from a 9-day course of ethanol vapor inhalation in male ddY mice

Basically If I'm not retarded they're suggesting that an increase in acetylation of the histone H3 protein is present in ethanol withdrawing rats. The acetylation is responsible for the adaptive changes to the both GABAa and GABAb receptor structure supposedly, only in some subunits though. This is why I want to source panobinostat.

The effect of a novel pentadecapeptide BPC 157 on development of tolerance and physical dependence following repeated administration of diazepam - PubMed

A novel gastric pentadecapeptide BPC 157 with different beneficial activities and anticonvulsant effect interacting with GABAergic system could improve diazepam efficacy coadministered (10 microg/kg, 10 ng/kg i.p.) with diazepam (5.0 mg/kg i.p.) twice daily for 10 days, since diazepam chronic...

pubmed.ncbi.nlm.nih.gov

A novel gastric pentadecapeptide BPC 157 with different beneficial activities and anticonvulsant effect interacting with GABAergic system could improve diazepam efficacy coadministered (10 microg/kg, 10 ng/kg i.p.) with diazepam (5.0 mg/kg i.p.) twice daily for 10 days, since diazepam chronic medication would otherwise predispose for diazepam- tolerance/withdrawal development (shorter latency to convulsion after convulsant). In diazepam chronically treated mice, it attenuated diazepam tolerance (provoked by later acute administration of diazepam together with convulsant) and postponed physical dependence/withdrawal effects (provoked by later administration of isoniazid)

Here's a good thread on Longecity:

BPC-157:fixes neurotransmitter systems - experiences? - Mental Health

BPC-157:fixes neurotransmitter systems - experiences? - posted in Mental Health: i found this on reddit and am curious to know if anyone has had any good experiences repairing their brains with BPC-157: https://www.reddit.c...as_a_nootropic/ from the link above: BPC-157 reduces tolerance...

www.longecity.org

Why are you trying to argue so adamantly that Parnate is better lol? It's objectively worse than Nardil for those who suffer with anxiety. Their side effect profile is marginally the same, you're going to go thru them initially regardless of either one you take.

People tolerate moais differently. Some hate Nardil because it's overly sedating and others don't like parnate because it's overly activating. The moa is obviously the exact same but there are slight differences obviously.

I don't think parnate is better but it's definitely more easily avaliable (outside of the USA) and phenelzine is barely produced in comparison to tranylcypromine. In Australia for example Phenelzine literally just got reintroduced after years of no longer being domestically produced/prescribed.

 

[russiancelreturns]

@Cope I don't know if you've seen these studies but they're incredibly interesting, especially for those using HDAC inhibitors.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3717553/

Basically If I'm not retarded they're suggesting that an increase in acetylation of the histone H3 protein is present in ethanol withdrawing rats. The acetylation is responsible for the adaptive changes to the both GABAa and GABAb receptor structure supposedly, only in some subunits though. This is why I want to source panobinostat.

The effect of a novel pentadecapeptide BPC 157 on development of tolerance and physical dependence following repeated administration of diazepam - PubMed

A novel gastric pentadecapeptide BPC 157 with different beneficial activities and anticonvulsant effect interacting with GABAergic system could improve diazepam efficacy coadministered (10 microg/kg, 10 ng/kg i.p.) with diazepam (5.0 mg/kg i.p.) twice daily for 10 days, since diazepam chronic...

pubmed.ncbi.nlm.nih.gov

Here's a good thread on Longecity:

BPC-157:fixes neurotransmitter systems - experiences? - Mental Health

BPC-157:fixes neurotransmitter systems - experiences? - posted in Mental Health: i found this on reddit and am curious to know if anyone has had any good experiences repairing their brains with BPC-157: https://www.reddit.c...as_a_nootropic/ from the link above: BPC-157 reduces tolerance...

www.longecity.org

People tolerate moais differently. Some hate Nardil because it's overly sedating and others don't like parnate because it's overly activating. The moa is obviously the exact same but there are slight differences obviously.

I don't think parnate is better but it's definitely more easily avaliable (outside of the USA) and phenelzine is barely produced in comparison to tranylcypromine. In Australia for example Phenelzine literally just got reintroduced after years of no longer being domestically produced/prescribed.

What about selegiline?

 

[Dyorotic]

What about selegiline?

selegiline is pretty good. It metabolises into levoamphetamine though iirc.

It's good for motivation and it's quite antidepressant but I don't think it does much for anxiety

 

[russiancelreturns]

selegiline is pretty good. It metabolises into levoamphetamine though iirc.

It's good for motivation and it's quite antidepressant but I don't think it does much for anxiety

So what do u think its the best for anxiety so far

 

[Cope]

I was looking into it a while ago. Just look it up. It isn't like Crebinostat tier but the BBB penetration is way higher than Vorinostat

I did, that's why I asked. All I could find was the difference in bioavailability, in which Vorinostat was higher:

Vorinostat | 43%
Panobinostat | 21%

What are you on about? I didn't even mention GABA-T. I just said that EVERYTHING that touches GABA in any way imaginble will cause adaptive changes and inevitable downregulation/desenistization. GABAergics are gross and should be avoided entirely if you like your sanity. Pregabalin clears all of them.

There are structural differences between GABAb and GABAa. BPC157, for example, has been shown to reverse tolerance on GABAb but does nothing for GABAa. Tolerance to baclofen is astoundingly low and I haven't seen many anecdotes of people having to increase dosage over time. But yeah it's just like anything GABA-related.

Why are you trying to school me on something I'm quite understanding of?

Inhibiting GABA-tramsaminase increases GABA's ability to inhibit action potential (well not literally but it'll increase the amount of GABA circulating in the brain), thus causing adaptive changes to the receptor(s) over time. Everything you proceeded to write has absolutely no bearing on whether or not the anxiolytic effect will wane, because it will. You're increasing GABA transmission, plain and simple. Just because it works uniquely to other gabaergic agents (receptor agonists, positive allosteric modulators & GAT-1 inhibitors) doesn't mean it won't invariably decrease the receptors responsiveness to GABA and cause an overcompensation of glutamate transmission (which might not be that bad because with GABA-T inhibition you're at least closer to homeostasis than using benzodiazepines).

So sure, GABA-tramsaminsae inhibition won't lessen the amount of GABA as an adaptive change but it'll cause tachyphylaxis just like any other substance. Increasing GABA via GABA-T inhibition = ↓ GABAa/b receptor sensitvity, increasing GABA transmission via allosteric modulation = ↓ GABAb/a sensitivity + a skewed GABA/glutmate profile. There isn't a fundamental difference here other than the fact that with phenelzine at least the glutamate/GABA ratio isn't violently skewed towards glutamate dominance, which is obviously optimal because it'll make withdrawals infinitely more tolerable.

School me because I seem to be missing something apparently. Interestingly Lamotrigine actually seems to decrease GABA transmission slightly, which just seems odd to me.

Nardil's mechanism of action is different from typical GABAergics and just because it's a "GABA-T inhibitor" that in no way means that it operates like conventional inhibitors of GABA-tramsaminase. It's based on levels of pyroxidine (B6) and phenethylidenehydrazine (PEH). It does not cause an overcompensation of glutamate transmission. Nardil creates a balance, and when there's a balance receptors aren’t overwhelmed or downregulated.

Nardil increases GABA levels in the brain, but there is not an increase in GABAergic transmission. As you can see from this study, despite the considerable increase in whole brain GABA levels in the PLZ-treated rats, there were no significant differences in GABAA or benzodiazepine receptor binding parameters (KD or Bmax) between the groups as measured using 3H-muscimol and 3H-flunitrazepam in radioligand binding assays.

You obviously do understand the pharmacology behind these mechanisms very well, I wasn't questioning that. I was simply stating that you weren't aware of and have an incorrect understanding of Nardil's effect on the GABAergic system.

There are structural differences between GABAb and GABAa. BPC157, for example, has been shown to reverse tolerance on GABAb but does nothing for GABAa. Tolerance to baclofen is astoundingly low and I haven't seen many anecdotes of people having to increase dosage over time. But yeah it's just like anything GABA-related.

I know, I previously just said GABA-B receptor agonists are more forgiving for this reason. I already stated Baclofen's half-life is short which is why tolerance is low. The reverse tolerance is negligible because something like the notorious GABA-B agent Phenibut causes rapid tolerance and withdrawal issues.

Can you give me an example? You can only augment so many times until your augmentation needs augmentation. Psych meds are a complete fucking joke.

Typically the best augments are actually supplements. Vitamin B6 (pyroxidine version) augments the GABAergic effect since GABA-transaminase is dependent upon it. L-Tryptophan works really to induce a calming aspect of Nardil since it competes with other trace amine neuromodulators like phenethylamine, which causes the amphetamine like effect you can get from it.

A lot of psychotropicals are enhanced with Nardil. Everything typically feels better. When I took Vorinostat with it, the experience was extremely calming and euphoric. I entered a meditative state on it. I had my best exposure therapy moments when I took them both together. Modafinil felt amazing on it, I had one of the most surreal days of life when I took them together. Lyrica was obviously great, nicotine was satisfying.

Of course a lot psych meds are used to augment. Lamictal, Amitriptyline, Amisulpride, etc. I never really went down that route. I've been on every psych med under the planet and ye they all suck except for like benzos, Lyrica, and Ketamine.

Brother I've been doing this for years. Ironically normalising dopaminergic transmission with aripiprazole gave me better results than using literal meth tbh.

Abilify, really? That med made feel so uncomfortable, I hate ATPs.

I found some on madeinchina and it's from the source I usually buy my raws from. If I get a batch I can send it to Janoshik for HPLC and I'd definitley be down to send you as much as you need for free. Lmk

It'd be pisscheap just like vstat most likely

lol Forreal? That would be a huge hook-up my dude, I'd definitely appreciate that if you could.

What's your disc btw? You seem to understand pharmacology really well and have a lot of experience with psychotropicals. You probably know a lot more than me about some of this stuff.

@Cope I don't know if you've seen these studies but they're incredibly interesting, especially for those using HDAC inhibitors.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3717553/

Basically If I'm not retarded they're suggesting that an increase in acetylation of the histone H3 protein is present in ethanol withdrawing rats. The acetylation is responsible for the adaptive changes to the both GABAa and GABAb receptor structure supposedly, only in some subunits though. This is why I want to source panobinostat.

Good find. It's interesting because I did notice Vorinostat helped somewhat when I was going thru benzo withdrawals. There appears to be a strong correlation between HDACis and the GABA-A subunits.

 

[Dyorotic]

Nardil increases GABA levels in the brain, but there is not an increase in GABAergic transmission

Okay. Yeah I had no clue about the b6 thing.

So how would something like Vigabatrin work? Same way? I found some and wanted to buy it but I've literally seen zero reports of it's use. Tiagabine also seems interesting.

I know, I previously just said GABA-B receptor agonists are more forgiving for this reason. I already stated Baclofen's half-life is short which is why tolerance is low. The reverse tolerance is negligible because something like the notorious GABA-B agent Phenibut causes rapid tolerance and withdrawal issues.

This is something that interests me. Pharmacologically there isn't any difference between Baclofen and Phenibut in terms of it's interaction and affinity towards GABAb. Phenibut's oral bioavailability is what necessitates such high dosages in comparison to Baclofen, and I've used Baclofen in conjunction with Pregabalin and the effect did not emulate that of Phenibut's whatsoever. Pregabalin's primary moa is through VGCC channel inhibiton which essentially just blocks the release of acetylcholine, dopamine, serotonin and glutamate.

I think the reason why withdrawals are infinitely worse with Phenibut than the aforementioned substances is that it acts as an antagonist at TAAR1 (Trace Amine-Associated Receptors 1). This is where it blocks the binding of the neurotransmitter B-Phenethylamine. Phenethylamine functions as the intermediary neurotransmitter, metabolising into neurotransmitters like L-DOPA, Dopamine, Epinephrine, Norepinephrine, Synephrine, and p-Octopamine (nardil iirc blocks the metabolism of some of these via MOA inhibition). It also acts as a fundamental structure for synthetic compounds called phenethylamines, stuff like amphetamines, substituted amphetamines, and certain cathinones. These drugs/neurotransmitters collectively stimulate the TAAR1 Receptor, leading to anxiety.

But it's also doing what Pregabalin is doing at the VGCC (leagues weaker than Pregabalin obviously) so you're essentially hitting three targets with Phenibut, all of which lead to less to substantially less neuronal firing. Hence why the withdrawals are nastier than Pregabalin or Baclofen alone (even worse than Pregabalin & Baclofen combined ime).

The "unstainability effect" from Phenibut isn't from it's GABAb agonism (which is just as strong as Baclofen's) but rather from the TAAR1 antagonism (and primarily through the VGCC antagonism).

Baclofen alone is probably one of the safest and most sustainable GABAergics. All the times I've come off (even after months of daily redosing) I was able to drop 10mg a day (I was at 100mg) and was off within 10 days. I used BPC157 and memantine during withdrawals.

Typically the best augments are actually supplements. Vitamin B6 (pyroxidine version) augments the GABAergic effect since GABA-transaminase is dependent upon it. L-Tryptophan works really to induce a calming aspect of Nardil since it competes with other trace amine neuromodulators like phenethylamine, which causes the amphetamine like effect you can get from it.

A lot of psychotropicals are enhanced with Nardil. Everything typically feels better. When I took Vorinostat with it, the experience was extremely calming and euphoric. I entered a meditative state on it. I had my best exposure therapy moments when I took them both together. Modafinil felt amazing on it, I had one of the most surreal days of life when I took them together. Lyrica was obviously great, nicotine was satisfying

You make it sound amazing tbh. I've spent a lot of time on the MOAi reddit and a lot of people there seem to have finally reached serenity so to speak. I think the best augmentation would just be phenidates and or/amphetamines. Lamotrigine seems to be one of the best psych meds but it literally gave me acne and my hair was falling out even on minoxidil and finasteride.

Amisulpride

This one interested me for a while. Doesn't it just antagonise autoreceptors which leads to an increase in Dopamine? I feel like that effect would wane over time because other autoreceptors (D3) would just detect an influx in Dopamine and shut everything down.

Abilify, really? That med made feel so uncomfortable, I hate ATPs.

Yeah It was a weird experience to say the least. It gave me a disgusting libido, never felt more consumed by sexual thoughts ever. Dropped it because it gave me akathesia. Was decent up until that point though, was very antidepressant (I don't have depression but I have really shocking OCD and it did nothing for that)

lol Forreal? That would be a huge hook-up my dude, I'd definitely appreciate that if you could.

Yeah with Janoshik I don't feel scared to purchase raws from china. I just send a batch to Janoshik and they almost always come back really high quality. I've gotten Lamotrigine raws, Clomipramine raws and Vorinostat as well.

What's your disc btw?

Discord is nick301775.

You probably know a lot more than me about some of this stuff.

Ah probably not. I actually learnt a lot from you back in the day (it's Dyorotic2 ahah)

Good find. It's interesting because I did notice Vorinostat helped somewhat when I was going thru benzo withdrawals. There appears to be a strong correlation between HDACis and the GABA-A subunits.

HDACi are actually incredibly fasinating. They're actually being studied at the moment for their potential ability to essentially rip the latent HIV cells out of the "reservoirs" and in conjunction with retroviral therapy destroy the replication forever. Panobinostat was the most effective out of all the hdaci.

HDACi are also used by PSSD suffers with some success.

 

[Dyorotic]

I did, that's why I asked. All I could find was the difference in bioavailability, in which Vorinostat was higher:

Panobinostat penetrates the blood–brain barrier and achieves effective brain concentrations in a murine model
Design, Synthesis, and Blood–Brain Barrier Transport Study of Pyrilamine Derivatives as Histone Deacetylase Inhibitors

Sorry, I can't find much regarding it's BBB penetration. But what I do know is Vorinostat's BBB penetration is really negligible and clinically insignificant. Any drug belonging to the hydroxamic acid class will have very low lipophilicity. Valproic acid, SAHA (vorinostat) and Panobinostat to name a few are all barely lipophilic

I think where Panobinostat shines is it's half life. I think using it infrequently and letting it bleed out of the system would be more optimal than using Vorinostat. Both are probably good though.

Valproate is good as well but it's such a dirty drug and highly hepatotoxic. It reacts strangely with hormone synthesis (majorly stimulates steroidogenesis) and antagonises androgen receptors.

 

[Cope]

Ah probably not. I actually learnt a lot from you back in the day (it's Dyorotic2 ahah)

Oh wow, what's up man long time no speak. Glad to see you're still around. Sorry for the delayed response, last week was very busy at work and I had some hectic events happen but I should be fine now.

Okay. Yeah I had no clue about the b6 thing.

So how would something like Vigabatrin work? Same way? I found some and wanted to buy it but I've literally seen zero reports of it's use. Tiagabine also seems interesting.

I actually was going to bring this up. I had a pdoc who I convinced to prescribe me Tiagabine. You would think that because it is a GABA reuptake inhibitor, it would be an absolute miracle drug for those who deal with anxiety/poor GABA signaling. But it was absolutely awful lol. Made my anxiety worse, gave me multiple panic attacks throughout the day, and brutal insomnia. This was from only 2mg too. I tried to push through it to see if I could possibly gain any potential benefit, but I couldn't do it and quit after 4 days. I spoke with a few guys on disc who also tried it and they had the same experience.

If I figure out why this was going on pharmacologically, I may revisit it again. I also want to try out Vigabatrin, doubt I could convince my current pdoc to prescribe it though.

This is something that interests me. Pharmacologically there isn't any difference between Baclofen and Phenibut in terms of it's interaction and affinity towards GABAb. Phenibut's oral bioavailability is what necessitates such high dosages in comparison to Baclofen, and I've used Baclofen in conjunction with Pregabalin and the effect did not emulate that of Phenibut's whatsoever. Pregabalin's primary moa is through VGCC channel inhibiton which essentially just blocks the release of acetylcholine, dopamine, serotonin and glutamate.

I think the reason why withdrawals are infinitely worse with Phenibut than the aforementioned substances is that it acts as an antagonist at TAAR1 (Trace Amine-Associated Receptors 1). This is where it blocks the binding of the neurotransmitter B-Phenethylamine. Phenethylamine functions as the intermediary neurotransmitter, metabolising into neurotransmitters like L-DOPA, Dopamine, Epinephrine, Norepinephrine, Synephrine, and p-Octopamine (nardil iirc blocks the metabolism of some of these via MOA inhibition). It also acts as a fundamental structure for synthetic compounds called phenethylamines, stuff like amphetamines, substituted amphetamines, and certain cathinones. These drugs/neurotransmitters collectively stimulate the TAAR1 Receptor, leading to anxiety.

But it's also doing what Pregabalin is doing at the VGCC (leagues weaker than Pregabalin obviously) so you're essentially hitting three targets with Phenibut, all of which lead to less to substantially less neuronal firing. Hence why the withdrawals are nastier than Pregabalin or Baclofen alone (even worse than Pregabalin & Baclofen combined ime).

The "unstainability effect" from Phenibut isn't from it's GABAb agonism (which is just as strong as Baclofen's) but rather from the TAAR1 antagonism (and primarily through the VGCC antagonism).

Baclofen alone is probably one of the safest and most sustainable GABAergics. All the times I've come off (even after months of daily redosing) I was able to drop 10mg a day (I was at 100mg) and was off within 10 days. I used BPC157 and memantine during withdrawals.

Interesting, had no idea Phen was a TAAR1 antagonist. But by blocking phenethylamine from binding, how does this make the withdrawals worse? From upregulation of the receptors? I do remember having pretty much zero withdrawals when I took Baclofen.

The build up of phenethylamine from taking Nardil is one of the main reasons why I had to quit. Nardil began to give me uncomfortable physical stimulation, which was likely from the metabolization into PEA. I believe this is due to the change in manufacturer. Nardil was an absolute godsend, but now that Lupin no longer manufactures it and the only options available in the states are the Greenstone and the Pfizer version it is no longer the gold standard IMO. This side effect started happening as soon as I was switched to Greenstone indefinitely. This is due to the Lupin version having more inactive ingredients than the Greenstone version, thus causing the pill to have a harder shell. There is less metabolization of PEA because the pill was being absorbed more in the small intestine rather than the stomach. This lowkey makes me want to reformulate it myself.

Ingredients difference:
Lupin

Ingredient Name	Strength
INACTIVE INGREDIENTS
MANNITOL (UNII: 3OWL53L36A)
SILICON DIOXIDE (UNII: ETJ7Z6XBU4)
POVIDONE (UNII: FZ989GH94E)
EDETATE DISODIUM (UNII: 7FLD91C86K)
MAGNESIUM STEARATE (UNII: 70097M6I30)
POLYVINYL ALCOHOL, UNSPECIFIED (UNII: 532B59J990)
POLYETHYLENE GLYCOL 3350 (UNII: G2M7P15E5P)
FD&C YELLOW NO. 6 (UNII: H77VEI93A8)
TALC (UNII: 7SEV7J4R1U)
TITANIUM DIOXIDE (UNII: 15FIX9V2JP)

Greenstone

Ingredient Name	Strength
INACTIVE INGREDIENTS
MANNITOL (UNII: 3OWL53L36A)
CROSCARMELLOSE SODIUM (UNII: M28OL1HH48)
POVIDONE, UNSPECIFIED (UNII: FZ989GH94E)
EDETATE DISODIUM (UNII: 7FLD91C86K)
MAGNESIUM STEARATE (UNII: 70097M6I30)
ISOPROPYL ALCOHOL (UNII: ND2M416302)
WATER (UNII: 059QF0KO0R)

I don't if you have any thoughts related to this. I tried to use L-tryptophan and other amino acids to create more trace amines to compete with PEA but this proved to be unsuccessful.

You make it sound amazing tbh. I've spent a lot of time on the MOAi reddit and a lot of people there seem to have finally reached serenity so to speak. I think the best augmentation would just be phenidates and or/amphetamines. Lamotrigine seems to be one of the best psych meds but it literally gave me acne and my hair was falling out even on minoxidil and finasteride.

The honeymoon phase of Nardil was honestly one of the greatest periods of my life. Felt like I was completely free mentally with zero fear, like childhood innocence. Never felt that much consistent euphoria and bliss for that long, it was roughly 6 months.

This one interested me for a while. Doesn't it just antagonise autoreceptors which leads to an increase in Dopamine? I feel like that effect would wane over time because other autoreceptors (D3) would just detect an influx in Dopamine and shut everything down.


Yeah It was a weird experience to say the least. It gave me a disgusting libido, never felt more consumed by sexual thoughts ever. Dropped it because it gave me akathesia. Was decent up until that point though, was very antidepressant (I don't have depression but I have really shocking OCD and it did nothing for that)

I may be in a minority, but I do not notice much difference mentally from taking dopamine receptor antagonists. I took Quetiapine for very a long time, but I couldn't tell you if my dopaminergic signaling was much different from what it is now. I don't react to dopamine agonists like Bromocriptine and Lisuride either.

Yeah with Janoshik I don't feel scared to purchase raws from china. I just send a batch to Janoshik and they almost always come back really high quality. I've gotten Lamotrigine raws, Clomipramine raws and Vorinostat as well.

Oh wow, good stuff. If you are able to get some Panobinostat, I definitely wouldn't mind sending you some funds for the hook up.

HDACi are actually incredibly fasinating. They're actually being studied at the moment for their potential ability to essentially rip the latent HIV cells out of the "reservoirs" and in conjunction with retroviral therapy destroy the replication forever. Panobinostat was the most effective out of all the hdaci.

HDACi are also used by PSSD suffers with some success.

They have so much therapeutic potential, and we're still in the early stages of knowing what HDACis are fully capable of.

Panobinostat penetrates the blood–brain barrier and achieves effective brain concentrations in a murine model
Design, Synthesis, and Blood–Brain Barrier Transport Study of Pyrilamine Derivatives as Histone Deacetylase Inhibitors

Sorry, I can't find much regarding it's BBB penetration. But what I do know is Vorinostat's BBB penetration is really negligible and clinically insignificant. Any drug belonging to the hydroxamic acid class will have very low lipophilicity. Valproic acid, SAHA (vorinostat) and Panobinostat to name a few are all barely lipophilic

I think where Panobinostat shines is it's half life. I think using it infrequently and letting it bleed out of the system would be more optimal than using Vorinostat. Both are probably good though.

Valproate is good as well but it's such a dirty drug and highly hepatotoxic. It reacts strangely with hormone synthesis (majorly stimulates steroidogenesis) and antagonises androgen receptors.

Yep, lipophilicity matters as well as the presence of specific transporters or efflux pumps.

 

[russiancelreturns]

Yeah with Janoshik I don't feel scared to purchase raws from china. I just send a batch to Janoshik and they almost always come back really high quality. I've gotten Lamotrigine raws, Clomipramine raws and Vorinostat as well.

can you DM a vendor

 

[Tallest person here]

@Cope @9898 its nice to see that you guys turned out to be old friends
can I just ask how come you guys need such pharmacology? Were you born this way or did something happen when u were young and now your brains are more messed up.

also ive read every page of the thread and I can't seem to find a solution for my problem and I know everyones neurochemistry can be different but:
I don't suffer from bad anxiety or depression for the most part, just not really nt cause I get a little anxious, like alcohol works well for me to be nt. do u guys have any suggestions on what to take? or if I should just not take anything? (I will be a little disappointed but if that's how it is then that's how it is)

 

[Dyorotic]

Oh wow, what's up man long time no speak. Glad to see you're still around. Sorry for the delayed response, last week was very busy at work and I had some hectic events happen but I should be fine now.


I actually was going to bring this up. I had a pdoc who I convinced to prescribe me Tiagabine. You would think that because it is a GABA reuptake inhibitor, it would be an absolute miracle drug for those who deal with anxiety/poor GABA signaling. But it was absolutely awful lol. Made my anxiety worse, gave me multiple panic attacks throughout the day, and brutal insomnia. This was from only 2mg too. I tried to push through it to see if I could possibly gain any potential benefit, but I couldn't do it and quit after 4 days. I spoke with a few guys on disc who also tried it and they had the same experience.

If I figure out why this was going on pharmacologically, I may revisit it again. I also want to try out Vigabatrin, doubt I could convince my current pdoc to prescribe it though.


Interesting, had no idea Phen was a TAAR1 antagonist. But by blocking phenethylamine from binding, how does this make the withdrawals worse? From upregulation of the receptors? I do remember having pretty much zero withdrawals when I took Baclofen.

The build up of phenethylamine from taking Nardil is one of the main reasons why I had to quit. Nardil began to give me uncomfortable physical stimulation, which was likely from the metabolization into PEA. I believe this is due to the change in manufacturer. Nardil was an absolute godsend, but now that Lupin no longer manufactures it and the only options available in the states are the Greenstone and the Pfizer version it is no longer the gold standard IMO. This side effect started happening as soon as I was switched to Greenstone indefinitely. This is due to the Lupin version having more inactive ingredients than the Greenstone version, thus causing the pill to have a harder shell. There is less metabolization of PEA because the pill was being absorbed more in the small intestine rather than the stomach. This lowkey makes me want to reformulate it myself.

Ingredients difference:
Lupin

Ingredient Name	Strength
INACTIVE INGREDIENTS
MANNITOL (UNII: 3OWL53L36A)
SILICON DIOXIDE (UNII: ETJ7Z6XBU4)
POVIDONE (UNII: FZ989GH94E)
EDETATE DISODIUM (UNII: 7FLD91C86K)
MAGNESIUM STEARATE (UNII: 70097M6I30)
POLYVINYL ALCOHOL, UNSPECIFIED (UNII: 532B59J990)
POLYETHYLENE GLYCOL 3350 (UNII: G2M7P15E5P)
FD&C YELLOW NO. 6 (UNII: H77VEI93A8)
TALC (UNII: 7SEV7J4R1U)
TITANIUM DIOXIDE (UNII: 15FIX9V2JP)

Greenstone

Ingredient Name	Strength
INACTIVE INGREDIENTS
MANNITOL (UNII: 3OWL53L36A)
CROSCARMELLOSE SODIUM (UNII: M28OL1HH48)
POVIDONE, UNSPECIFIED (UNII: FZ989GH94E)
EDETATE DISODIUM (UNII: 7FLD91C86K)
MAGNESIUM STEARATE (UNII: 70097M6I30)
ISOPROPYL ALCOHOL (UNII: ND2M416302)
WATER (UNII: 059QF0KO0R)

I don't if you have any thoughts related to this. I tried to use L-tryptophan and other amino acids to create more trace amines to compete with PEA but this proved to be unsuccessful.


The honeymoon phase of Nardil was honestly one of the greatest periods of my life. Felt like I was completely free mentally with zero fear, like childhood innocence. Never felt that much consistent euphoria and bliss for that long, it was roughly 6 months.


I may be in a minority, but I do not notice much difference mentally from taking dopamine receptor antagonists. I took Quetiapine for very a long time, but I couldn't tell you if my dopaminergic signaling was much different from what it is now. I don't react to dopamine agonists like Bromocriptine and Lisuride either.


Oh wow, good stuff. If you are able to get some Panobinostat, I definitely wouldn't mind sending you some funds for the hook up.


They have so much therapeutic potential, and we're still in the early stages of knowing what HDACis are fully capable of.


Yep, lipophilicity matters as well as the presence of specific transporters or efflux pumps.

Juicy reply. I'd respond but we already spoke on discord.

@Cope @9898 its nice to see that you guys turned out to be old friends
can I just ask how come you guys need such pharmacology? Were you born this way or did something happen when u were young and now your brains are more messed up.

also ive read every page of the thread and I can't seem to find a solution for my problem and I know everyones neurochemistry can be different but:
I don't suffer from bad anxiety or depression for the most part, just not really nt cause I get a little anxious, like alcohol works well for me to be nt. do u guys have any suggestions on what to take? or if I should just not take anything? (I will be a little disappointed but if that's how it is then that's how it is)

I experienced rapid onset ocd in late 2021 and have been a wreck since. I'm completely enslaved by my particular theme of OCD.

Anyway, I was definitely born with it. Looking back there were definite signs as a kid.

Everyone had different neurochemistry and pharmogenomics. For me personally It seems I have an over production of Glutamate, so I've settled with glutamate modulating drugs. I don't recommend using anything gabaergic.

 

[russiancelreturns]

@Cope what other drugs inhibit GABA-T consistently? I wanna take lyrica on a daily basis. Unfortunately getting phenelzine is impossinle. Parnate and selegiline does not inhibit GABA-T.
Lyrica is a godsend ngl

 

[russiancelreturns]

so I've settled with glutamate modulating drugs

Which drugs to be more precise?

 

[Cope]

@Cope what other drugs inhibit GABA-T consistently? I wanna take lyrica on a daily basis. Unfortunately getting phenelzine is impossinle. Parnate and selegiline does not inhibit GABA-T.
Lyrica is a godsend ngl

Vigabatrin specifically inhibits GABA-T. But I have seen very few ancedotals of its use for anxiety and I have no idea if it would actually help if taken. I took Tiagabine which is a GABA reuptake inhibitor and had a negative reaction to it.

@9898 made a good point about glutamate modulation. Something like Riluzole might be worth considering more. All of these drugs are obscure and are not easy to source or get prescribed.

 

[Cope]

@Cope @9898 its nice to see that you guys turned out to be old friends
can I just ask how come you guys need such pharmacology? Were you born this way or did something happen when u were young and now your brains are more messed up.

also ive read every page of the thread and I can't seem to find a solution for my problem and I know everyones neurochemistry can be different but:
I don't suffer from bad anxiety or depression for the most part, just not really nt cause I get a little anxious, like alcohol works well for me to be nt. do u guys have any suggestions on what to take? or if I should just not take anything? (I will be a little disappointed but if that's how it is then that's how it is)

Lyrica is what works best for me. I do have GAD which Lyrica does not completely remove, but it gives me enough of a buffer to not socially overthink every interaction thus making me more NT. It makes me way more spontaneous, makes my words flow together better, and actually interested in otherwise trivial convos. I do think NT behavior comes from practice and learning a lot from past social interactions in order to succeed in conversation. I am very socially adept as my current job requires me to be so, but I couldn't do it without Lyrica.

Btw another user PMed me asking what my daily stack/routine is so I'll repost it here ig:

Morning
Lyrica 300mg
Take in the morning on an empty stomach with 200mg of caffeine

Phenylpiracetam 100mg
As needed if I need more of a mental/energy boost

Zyn Nicotine Pouches 3mg
Take throughout the day for energy and to surpress hunger

Librium 5mg
As needed if anxiety gets too overbearing

*I intermittent fast until around 2-3pm, this is crucial to get the most out of my Lyrica dose.

Afternoon
Lyrica 150mg
Take 1 hour before the gym on an empty stomach

Tadalafil 5mg
Take 1 hour before the gym

Evening
Librium 5mg
As needed for anxiety

As you can see, it's not much cuz I am trying to rawdog it a bit more. But the social god mode stack for me was Nardil 60mg + Lyrica 300mg + Vorinostat 50mg.

 

[russiancelreturns]

Vigabatrin specifically inhibits GABA-T. But I have seen very few ancedotals of its use for anxiety and I have no idea if it would actually help if taken. I took Tiagabine which is a GABA reuptake inhibitor and had a negative reaction to it.

@9898 made a good point about glutamate modulation. Something like Riluzole might be worth considering more. All of these drugs are obscure and are not easy to source or get prescribed.

So how would you run Tiagabine alongside with Lyrica? I wanna try it. Getting Nardil is impossible, hence I have nothing to lose

 

[russiancelreturns]

Morning
Lyrica 300mg
Take in the morning on an empty stomach with 200mg of caffeine

Phenylpiracetam 100mg
As needed if I need more of a mental/energy boost

Zyn Nicotine Pouches 3mg
Take throughout the day for energy and to surpress hunger

Librium 5mg
As needed if anxiety gets too overbearing

*I intermittent fast until around 2-3pm, this is crucial to get the most out of my Lyrica dose.

Afternoon
Lyrica 150mg
Take 1 hour before the gym on an empty stomach

Tadalafil 5mg
Take 1 hour before the gym

Evening
Librium 5mg
As needed for anxiety

Wheres nardil here?

 

[Tallest person here]

Lyrica is what works best for me. I do have GAD which Lyrica does not completely remove, but it gives me enough of a buffer to not socially overthink every interaction thus making me more NT. It makes me way more spontaneous, makes my words flow together better, and actually interested in otherwise trivial convos. I do think NT behavior comes from practice and learning a lot from past social interactions in order to succeed in conversation. I am very socially adept as my current job requires me to be so, but I couldn't do it without Lyrica.

Btw another user PMed me asking what my daily stack/routine is so I'll repost it here ig:

Morning
Lyrica 300mg
Take in the morning on an empty stomach with 200mg of caffeine

Phenylpiracetam 100mg
As needed if I need more of a mental/energy boost

Zyn Nicotine Pouches 3mg
Take throughout the day for energy and to surpress hunger

Librium 5mg
As needed if anxiety gets too overbearing

*I intermittent fast until around 2-3pm, this is crucial to get the most out of my Lyrica dose.

Afternoon
Lyrica 150mg
Take 1 hour before the gym on an empty stomach

Tadalafil 5mg
Take 1 hour before the gym

Evening
Librium 5mg
As needed for anxiety

As you can see, it's not much cuz I am trying to rawdog it a bit more. But the social god mode stack for me was Nardil 60mg + Lyrica 300mg + Vorinostat 50mg.

Cheers
Just tried Modafinil and it does everything I want it to do, I can speak easier and I feel more nt and I’m just locked in when I study. It doesn’t have like a kick in it’s more subtle which is kind of good I guess

 

[Tallest person here]

Lyrica is what works best for me. I do have GAD which Lyrica does not completely remove, but it gives me enough of a buffer to not socially overthink every interaction thus making me more NT. It makes me way more spontaneous, makes my words flow together better, and actually interested in otherwise trivial convos. I do think NT behavior comes from practice and learning a lot from past social interactions in order to succeed in conversation. I am very socially adept as my current job requires me to be so, but I couldn't do it without Lyrica.

Btw another user PMed me asking what my daily stack/routine is so I'll repost it here ig:

Morning
Lyrica 300mg
Take in the morning on an empty stomach with 200mg of caffeine

Phenylpiracetam 100mg
As needed if I need more of a mental/energy boost

Zyn Nicotine Pouches 3mg
Take throughout the day for energy and to surpress hunger

Librium 5mg
As needed if anxiety gets too overbearing

*I intermittent fast until around 2-3pm, this is crucial to get the most out of my Lyrica dose.

Afternoon
Lyrica 150mg
Take 1 hour before the gym on an empty stomach

Tadalafil 5mg
Take 1 hour before the gym

Evening
Librium 5mg
As needed for anxiety

As you can see, it's not much cuz I am trying to rawdog it a bit more. But the social god mode stack for me was Nardil 60mg + Lyrica 300mg + Vorinostat 50mg.

Cheers
Just tried Modafinil and it does everything I want it to do, I can speak easier and I feel more nt and I’m just locked in when I study. It doesn’t have like a kick in it’s more subtle which is kind of good I guess