Big exam next summer - which of these research compounds are worth it for acute focus/memory + long-term pro cognitive effects? Amounts okay?

[u/Mysterious-Milk-1201]

Hey everyone,
I've got a big test coming up next year July and I'm trying to prep with a mix of things for acute effects (focus, memory, attention, learning) plus some longer-term cycling for "hardware" support. My cart is expensive, so before I pull the trigger I wanted to run the full list by people who've looked into this stuff.
Here's everything currently in the cart and the quantities:
\-Usmarapride oxalate - 2 g
\-BPN14770 - 3 × 300 mg (900 mg total)
\-Oxiracetam - 2 × 60 g (120 g total)
\-Tropisetron - 4 × 200 mg (800 mg total)
\-Citicoline - 5 × 20 g (100 g total)
\-Bromantane - 2 spray bottles (each \~180 sprays at \~9 mg/spray)
\-Coluracetam - 2 × 2 g (4 g total)
\-NA-Semax - 2 bottles (100 sprays/bottle at 200 mcg/spray)
\-Paraxanthine - 3 × 15 g (45 g total)
\-TAK-653 - 3 × 60 mg (180 mg total)
\-Aniracetam - 2 × 50 g (100 g total)
\-NSI-189 freebase - 3 × 1200 mg (3600 mg total)
\-PRL-8-53 - 2 × 300 mg (600 mg total)
\-Pramiracetam - 1 pack of 18 g
\-GB-115 - 2 bottles (100 sprays/bottle at \~200 mcg/spray)
Goals are pretty straightforward: solid acute support for studying/learning when I need it, and the option to cycle a few things that might help longer-term.
If you were in my position (or if money were no object) which of these would you actually keep? Which ones would you completely drop? And which of these amounts would you increase? Are any of the amounts way off (too much or too little for a reasonable trial period)? Open to suggestions on adjusting package counts too.
Appreciate any thoughts, experiences, or red flags.
Thanks guys and women!

[u/Excellent-Radio-3106]

Genuinely curious on this stack. Like u just wanna try shit out? Most are without evidence for cognitive improvement in healthy ppl.

But besides id keep citicoline, prl and tak. Maybe paraxanthine.

How old are you if u dont mind me asking

[u/Mysterious-Milk-1201 → u/Excellent-Radio-3106]

This’ll be a long answer because I’ll be very precise and I think people should actually have a look into the data instead of dismissing these compounds and my interest out of ignorance or because of no knowledge. I’m 21 studying neuroscience. I’m just immensely fascinated by the brain and how these compounds interact with it. It’s basically my absolute rabbit hole, I spend hours reading studies and digging into this stuff because I just genuinely love it. So yes I want to try some of it out because I get to try these fascinating compounds in person
You’re right that most of them don’t have solid evidence for cognitive improvement in healthy people. But that’s because the FDA and therefore pharma companies test for treating diagnosed illnesses (depression, dementia, etc.)andnot for optimizing healthy brains. So if it doesn’t hit the primary endpoint for a disease it often simply gets dropped even if there are other strong signals, there’s also a financial side as it takes big amounts of money to get something through trials and approved but the fda mainly approves things that treat specific illnesses. That doesn’t mean the mechanisms stop working.
The mechanisms dont lie!! and a lot of these do have human data on cognition. For example my cart list:

UsmaraprideOxalate is a 5-HT4
receptor partial agonist. Activating 5-HT4 receptors increases acetylcholine release in the brain (which is important for memory and attention btw) and also raises levels of sAPPα (a protective form of the amyloid precursor protein) plus BDNF. In animal models it improved several types of memory (episodic, working, emotional) and reversed scopolamine-induced memory problems. Phase 1 in healthy people was completed and it was described as safe and well tolerated. +Phase 2 is planned. So more acetylcholine plus neurotrophic support is why the preclinical cognitive effects look strong in practice that can mean better focus, clearer thinking and also easier learning.
PRL-8-53 There’s only one small doubleblind study from 1978
With about 47 people). A single 5 mg dose improved verbal memory retention. Overall 24-hour recall was about 40% better than placebo and the recall after 1 week about 47% better.and in people over 30 or with weaker baseline memory the improvements were much much larger around 100%+ better at 24 hours and up to ~150% better at one week in some subgroups. High performers didn’t improve much though. No side effects were reported in that study but there is essentially no modern safety data and almost no other human research. As the development stopped decades ago, researcher retired + institutional issues not because of clear toxicity signals. The big memory retention boost is why people talk about it but the lack of safety data a main reason to be extremely cautious.

NSI-189 is an incredibly interesting compound. It failed its main depression goal in Phase 2, but secondary cognitive tests did improve. On cogScreen effect sizes for certain memory and executive measures reached around 0.7-1.1 (medium to large). The most incredible thing: in mice it increased hippocampal volume by ablut 36% at one dose and even higher at another. Human mri changes were smaller though and not clearly significant but the neurogenesis angle is why it’s very looked at. And because more hippocampal growth and plasticity can support better memory formation and learning over time.

Moving on to a favorite of mine, tak653 an AMPA receptor positive modulator. In a Phase 2 depression trial the 1 mg dose reduced MADRS scores by about 4.3 points at day 28 and ~ 6.9 to7.5 points at day 56 versus placebo (effect size is around 0.7). In healthy subjects it increased corticospinal excitability on TMS, which is consistent with the mechanism. Preclinical data is strongly pro-cognitive via AMPA, BDNF/mTOR plasticity. Better AMPA signaling improves focus, mental energy and the ability to form new connections while learning

Bpn14770 blocks the PDE4D enzyme, this raises cAMP levels which supports long-term potentiation (the process that strengthens memory connections) and also CREB signaling. Stronger LTP and CREB activity means better focus, memory consolidation +the ability to hold information while working. In a Phase 2 trial in adults with Fragile X it improved NIH Toolbox scores: oral reading recognition +2.81 points, picture vocabulary +5.81, crystallized composite +5.31. Caregivers also rated language about +14 points and daily functioning about +14.5 points higher on 100-point scales. Effects lasted even after the crossover.

tropisetron is an approved medicine in many countries as an antiemetic. It also sensitizes α7 nicotinic receptors which are involved in attention and sensory processing. In schizophrenia studies, short-term use improved overall cognitive scores (RBANS) with medium to large effects at certain doses (Cohen’s d around 0.5-1.4 depending on dose and measure) and also helped normalize sensory gating. The a7 effect isn’t limited to schizophrenia patients because the same pathway supports attention and sensory filtering in general. That translates to clearer focus and better ability to ignore distractions

Citicholine is actually self explanatory but nvm: it is naturally present in the brain where it provides choline and supports cell membranes and supplementing Citicholine supports acetylcholine and membrane health, which helps with both memory and sustained focus!
For coffee enthusiasts (including me): Paraxanthine: The main metabolite of caffeine (most caffeine turns into it,80%). In healthy people 200 mg reduced errors on the Berg-Wisconsin Card Sorting Test by roughly 17-33% fewer perseverative errors at certain time points and it improved reaction time and sustained attention on vigilance tasks compared to placebo. data even showed better postexercise cognitive performance than caffeine itself on specific measures. Upsides? Yes cleaner focus and better sustained attention!
Oxiracetam: In a large trial in mild to moderate traumatic brain injury patients, the L-form improved cognitive assessment scores a lot more than placebo at 90 days (roughly a 9 point advantage on the LOTCA scale). Older dementia studies also showed benefits on memory and attention. Because it supports brain energy metabolism so ATP and cholinergic function. More brain energy and better cholinergic signaling leads to a stronger focus, a lot more mental stamina and easier learning
Pramiracetam, older placebo controlled work in young men with memory problems after head injury showed significant improvements in delayed recall compared to placebo and the benefit lasted in longer follow-up. It strongly enhances high-affinity choline uptake in the hippocampus. In my own experience it produced laser focus, I was able to learn and memorize a large amount of university material in a short time because the increase in focus and absorption felt dramatic. The mechanism again does not lie: stronger hippocampal choline uptake can support both memory formation and intense sustained focus while studying.

Bromantane is registered in Russia for fatigue/asthenia. In a large Russian study of 728 patients, about 91% were rated improved after 28 days. In studies it was shown to upregulate the enzymes that make dopamine. tyrosine hydroxylase expression can rise 2-2.5-fold in certain regions), increasing the brain’s capacity to produce dopamine rather than just dumping existing stores. Like Amphetaminen do (very bad and unhealthy!) but why would you want to increase dopamine? Because higher dopamine availability supports motivation, drive + the ability to stay engaged with learning or work. Also Side effects were uncommon as with actually almost all of these compounds.

Semax is another registered medication in russia for stroke and cognitive issues. It raises BDNF. Which is the growth factor that helps neurons form and strengthen connections with each other. More BDNF supports better learning and memory consolidation and recovery of cognitive function after stress or injury. And It has clinical data for cognitive recovery after brain injury

So the mechanisms (more acetylcholine, AMPA modulation, cAMP that leads to better LTP, α7 nicotinic, dopamine upregulation, BDNF, etc) do not lie! Which is why these are interesting. Also thanks for your advice and recommendations!

[u/Calm_Stomach6597]

man that cart is wild, drop the aniracetam at least, it's barely bioavailable without fat and the effect is so subtle you might as well be sniffing a candle. keep the NA-Semax and bromantane for sure, they actually do something you can feel in the focus department and stack nice together. for long term i would hold onto NSI-189 but the rest of this list reads like you're trying to build a spaceship out of supplements nobody properly studied

[u/Mysterious-Milk-1201 → u/Calm_Stomach6597]

Hahaha you’re hilarious and not wrong the cart does look like I’m trying to reverse engineer a human brain with stuff that has either weird studies or none at all. I’ll drop aniracetam, thanks. And I’ll definitely keep the Semax, Bromantane and Nsi-189. and i’ll think about aggressively auditing the rest before I invent a new psychiatric condition
Appreciate the honesty!

[u/LOL-Enforcement]

I’d say check out PRL-8-53 for sure, specifically for recall.

[u/Mysterious-Milk-1201 → u/LOL-Enforcement]

I’ll definitely give it a few tries but no more than that. With the lacking safety data it simply is not worth it

[u/Icy_Sherbet2134]

I take noopept and it works great

[u/Mysterious-Milk-1201 → u/Icy_Sherbet2134]

Tried it as well, works nicely

[u/Surive123]

I went through a similar phase as you and dabbled a bit. From personal experience, I'd ditch the BPN14770, Tropisetron, Coluracetam, NSI-189 freebase, Aniracetram, GB-115, TAK-653. I picked up PRL 8-53 like 10 years ago on a whim, and seeing how it is recommended nowadays, man I got lucky. I had gotten to a point where I was trying to convince myself that PRL was a placebo, but I couldn't really deny it anymore.

Pramiracetam is fine, but I'd just do the tried and true phenylpiracetam. Also appreciate sublingual moda. Consider all that and our stacks would be pretty similar after a lot of trial and error.

[u/Mysterious-Milk-1201 → u/Surive123]

How did PRL 8-53 work for you?

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