Need Sustainable Nootropics For Mental Acuity

[Terma]

So, I'm posting this after a sleepless night. I'm doing this intentionally while my judgment is impaired because I don't have the emotions available on hand to feel like a hypocrite asking for help from a forum I indirectly criticized one hour ago.

I'll skip the worst of my medical history because most people don't even believe me. My life cartoonishly insane. The relevant parts are: In my teens I was an overachiever. Early 20s my cognition started going downhill. I found no real improvement until about 2 years ago using opioids and tianeptine and to an extent, 5a-DHP. However the opioids impair some parts of cognition, not unlike NMDA antagonism (tianeptine was reported to have NMDA antagonistic effects, though I question the nature of this due to a 2017 study placing its anti-depressive effect squarely on opioid activity).

Ultimately the only thing to restore my mental abilities from 10 years ago has been Phenibut. In fact it's been so positive in my life recently, it's given me a sense of empathy I can't even recall having before. I become literally a better person on it. I suspect that's driven by either 5-ht2a, vasopressin and/or oxytocin, but I have very little to back that up (one big hint is I get polyuria which likely influenced by low vasopressin), except the n=1 reports from MDMA users likening it to Phen. Don't conflate my ramblings on this forum with the usual reports others make about Phenibut making them ***holes due probably to norepinephrine increase; the worst of mine were from alcohol, which was usually a destructive force in my life, although it did very temporarily relieve symptoms of mine.

However Phenibut is unsustainable due to its insanely long half-life (I'm convinced the literature underestimates it somehow), and it is clearly increasing stress hormones and cortisol - in part due to interference with sleep likely coming from norepinephrine increase - and I've been noticing cardiac symptoms. It will not only shorten my life by 10 years, but possibly end up killing me.

So I need more sustainable nootropics. Before this goes into territory I've already covered: I've already tried every diet variation on the planet, and mega-doses of most vitamins (B1 B2 B3 B52 etc.). This is due to my health issues which are likely immune-driven and immune to dietary and lifestyle fixes. Unfortunately Ray Peat diet has limits. Most likely the only bearing it could possibly have on it is from gut modulation; I've already recently improved my gut in part thanks to adamantane.

So to give you an idea, here are some things I've tried that almost work, and some of these I still try to take:
* Fasoracetam
* Sarcosine (NMDA agonist - very similar to glycine - it's methylated glycine - but opposite effects on me from glycine, which clearly compromises my thinking)
* Alpha-GPC - to a limited extent

In theory pregnenolone or DHEA could work because they have NMDA agonistic effects [Pregnenolone] [DHEA] but it's not very noticeable. Maybe the dosage or sulfated forms end up interfering.

Something that's quite clear: NMDA antagonists reliably inhibit some parts of my cognition. And most likely I already acquired a predisposition toward NMDA hypo-activation from immune issues or even from birth to a limited extent (e.g., Kynurenic acid is known to do this; it's an issue in schizophrenia though I'm not schizophrenic [yet]; it may also be an issue in OCD, which I may have developed or always had a little, albeit undiagnosed and a little at odds with my pre-20s mental abilities).

Avoiding nitric oxide is definitely stimulating to my brain. I think that increasing glutamate while inhibiting nitric oxide is one strategy, but am afraid could be damaging.

There are still a ton of things I haven't tried. I'm not even sure this is the right crowd but I won't get much from Longecity. I tried all the racetams except coluracetam, coming in the mail. I still haven't tried NSI-189. Well that's about it. I'm surprised I managed to write this much. That's Phenibut!

 

[Terma]

Oh boy, I completely forgot. Phenibut failed me, noooooooo...

One of the best nootropics I've tried is PRL-8-53. According to a single study by the patent holder, it's a dopamine and acetylcholine agonist and serotonin antagonist. It's some kind of benzoic acid derivative (@haidut that might interest you).

Subjectively it's an awesome supplement, but it has to be cycled to a frequency similar to Phenibut otherwise it loses effect.

It's basically what everyone expects Piracetam to be but never was.

 

[Terma]

Oh yeah and I'm one of those people for which Thyroid hormone never worked and only backfires. My numbers weren't that bad for somebody with so many problems anyway (fluctuates between 1.5 and 2.2)

[Testosterone middle range]

[T4 & T3 surprisingly good; couldn't get rT3 test where I live]

 

[Arrade]

Ginkgo biloba

 

[Terma]

Thanks for answering.

I did try Gingko. Well, one brand anyway. It almost seemed to help but I felt very off on it. I think it's because it has a blood thinner effect, and I do poorly on those (and yes I know about vitamin K; doesn't seem to be my issue). But I'm not sure.

 

[opethfeldt]

Why do you suspect Phenibut is increasing stress hormones? If anything, it should lower them via the GABA increase. It is prescribed to astronauts in Russia specifically for stress management, after all.

 

[Terma]

Research-wise it's dose-dependent. There's some research that shows for example that GABAB agonists such as Baclofen can increase cortisol (similar to how it increases growth hormone) in higher doses, or specific doses. I also suspect some of its reported effects suggest increased serotonin signaling, along the lines of MDMA - which almost necessarily implies increased cortisol - but that is still speculation on my part.

The more tangible reason is just n=1 and the clear increase in norepinephrine together negative effect on sleep from some dosages and inappropriate chronic use (me right now).

Right now it's noticeably delaying healing and impacting my joints.

[Unrelated: My cardiovascular system feels totally off right now; if I disappear for a month and never post again... I almost surely croaked]

 

[Arrade]

Research-wise it's dose-dependent. There's some research that shows for example that GABAB agonists such as Baclofen can increase cortisol (similar to how it increases growth hormone) in higher doses, or specific doses. I also suspect some of its reported effects suggest increased serotonin signaling, along the lines of MDMA - which almost necessarily implies increased cortisol - but that is still speculation on my part.

The more tangible reason is just n=1 and the clear increase in norepinephrine together negative effect on sleep from some dosages and inappropriate chronic use (me right now).

Right now it's noticeably delaying healing and impacting my joints.

[Unrelated: My cardiovascular system feels totally off right now; if I disappear for a month and never post again... I almost surely croaked]

What’s wrong with your cardio? You should supplement 230 mcg mk7

 

[opethfeldt]

Interesting. I never heard about any pro-serotonin effects of Phenibut, just increased dopamine production and increase in GABA B.

 

[Terma]

What’s wrong with your cardio? You should supplement 230 mcg mk7

Not sure, strange combination of feelings. I already ate a bunch of greens and took 15 drops of mk4 today. But it does nothing noticeable.

That said I might have made this worse by taking some vitamin E before eating some salmon sushi. But the K really does nothing for me despite that, I only take some preventatively. I'm not sure what's doing this, it was already getting screwed up before eating. Now I'm rambling. I'm just scared if I die tonight nobody's going to know my cat is alone.

 

[Arrade]

Not sure, strange combination of feelings. I already ate a bunch of greens and took 15 drops of mk4 today. But it does nothing noticeable.

That said I might have made this worse by taking some vitamin E before eating some salmon sushi. But the K really does nothing for me despite that, I only take some preventatively. I'm not sure what's doing this, it was already getting screwed up before eating. Now I'm rambling. I'm just scared if I die tonight nobody's going to know my cat is alone.

“The Prospect Study demonstrated an inverse correlation between intake of K2 (MK-7, MK-8 and MK-9) and the risk of coronary heart disease. The long-chain forms of K2 (MK-7 and higher), were shown to have the most beneficial effects on the prevention of coronary heart disease, with a mortality risk reduction of 9% for each extra 10µg/day intake”
https://www.nutraceuticalbusinessre...nd_treatment_of_arterial_calcification/123944
Mk7 is the one for cardio health, I think this forum gets this wrong

Also 15 drops of mk4 is really high, it can definitely throw you out of balance. I had strong effects at 45 mg
Try doing some walking/jogging and exercise your vascular system, it might help calm things down

 

[Energizer]

Have you had your thyroid checked, OP? That's usually the 1st thing to go before mental performance drops. As far as supplements I can't comment on those I've only had good results with methylene blue and pregnenolone, they both seem to reduce stress, especially pregnenolone. BTW, there isn't a "Ray Peat diet", that's a common misconception to people who don't understand that he doesn't try to be some kind of guru or authority. In my opinion you get a lot more milage by checking thyroid function before you even begin supplementation because if your thyroid is good chances are you will have few mental performance issues.

 

[haidut]

Oh boy, I completely forgot. Phenibut failed me, noooooooo...

One of the best nootropics I've tried is PRL-8-53. According to a single study by the patent holder, it's a dopamine and acetylcholine agonist and serotonin antagonist. It's some kind of benzoic acid derivative (@haidut that might interest you).

Subjectively it's an awesome supplement, but it has to be cycled to a frequency similar to Phenibut otherwise it loses effect.

It's basically what everyone expects Piracetam to be but never was.

It looks interesting but I would like to see more data on its cholinergic properties. Though, it is encouraging that it did not potentiate the effects of amphetamines, so it is probably less toxic than those.

 

[Terma]

“The Prospect Study demonstrated an inverse correlation between intake of K2 (MK-7, MK-8 and MK-9) and the risk of coronary heart disease. The long-chain forms of K2 (MK-7 and higher), were shown to have the most beneficial effects on the prevention of coronary heart disease, with a mortality risk reduction of 9% for each extra 10µg/day intake”
https://www.nutraceuticalbusinessre...nd_treatment_of_arterial_calcification/123944
Mk7 is the one for cardio health, I think this forum gets this wrong

Also 15 drops of mk4 is really high, it can definitely throw you out of balance. I had strong effects at 45 mg
Try doing some walking/jogging and exercise your vascular system, it might help calm things down

Hmmm, I did not know that. I used to take mk7 but not recently. Maybe mk4 is a huge waste of money for that goal. However I also wonder if that conclusion is not influenced by the supplement companies?

I can't do that type of exercise (eroded joints from fluoroquinolone toxicity). I'm going to go lie down on my right side. I way overdid it.

Have you had your thyroid checked, OP? That's usually the 1st thing to go before mental performance drops. As far as supplements I can't comment on those I've only had good results with methylene blue and pregnenolone, they both seem to reduce stress, especially pregnenolone. BTW, there isn't a "Ray Peat diet", that's a common misconception to people who don't understand that he doesn't try to be some kind of guru or authority. In my opinion you get a lot more milage by checking thyroid function before you even begin supplementation because if your thyroid is good chances are you will have few mental performance issues.

Thanks but yeah Need Sustainable Nootropics For Mental Acuity

It's not optimal but it's not that bad, unless rT3

It looks interesting but I would like to see more data on its cholinergic properties. Though, it is encouraging that it did not potentiate the effects of amphetamines, so it is probably less toxic than those.

I know [there's so little support for it or info on cholinergic properties]. The only other supporting factor is the inventor says he's been using it on himself his whole life with no issues.

Subjectively, besides the dopamine and antidepressant effect, it feels like either increased acetylcholine or NMDA signaling (the NMDA agonism is not bad at all in my opinion - even the steroids do it). I have trouble differentiating the two. I'm not too concerned; piracetam is also popularly thought to increase cholinergic signaling but it has good effects on mitochondrial function in compromised individuals so it's the net effect I look for. Clearly users need to take breaks from it though.

The NMDA seems like a plausible alternative explanation to me because of this:
Potential Safety Issues Surrounding the Use of Benzoate Preservatives

By acting to increase the levels of D-serine in various brain areas benzoate is thought to increase NMDA receptor activity.

(D-serine like sarcosine appears beneficial for schizophrenia, and sarcosine definitely benefits me - I think it's fine as long as nNOS production is controlled, possibly also iNOS)

 

[Energizer]

You could also try restricting tryptophan (to lower serotonin) and taking high doses of niacinimide, a lot cheaper than research chemicals. You could also experiment with red lights. In addition to the adamantane for your gut you could also try antibiotics (low dose penicillin or minocycline), I assume you do the carrot salad daily but that helps, bamboo shoots if you need a more robust antibiotic fiber. Frankly, I feel great drinking lots of coffee. Surprised you're all into nootropics but don't mention strong coffee, it's way better than any nootropic that comes to mind and it's cheap.

Here on this forum nootropics get mentioned but don't think they don't get the same emphasis as a place like longecity because people here seem more more aware of the limitations of the smart drug culture which focuses all on smart drugs and ignores the endocrine system and nutrition. If you're really desperate you could always email Ray and ask him what his recommendation would be.

 

[Terma]

Yeah they give people a bad taste in their mouth here, what do you do when no diet or lifestyle change publicized on planet earth affects your condition? And you still have to work and survive?

Antibiotics are part of what got me into this mess. Why I have to look into non-antibiotic gut solutions. It's already much better now though.

I relied on pure caffeine for ages (coffee screws me up), but recently it started setting me back. (It's impressive combined with Phenibut btw, but then forget about sleep [might as well do meth])

I never emailed Ray. I agree with him on a lot of things, but it takes so long to describe my problems and he replies with one liners.

(so, didn't die)

 

[Terma]

I do prefer nootropics that have at least one metabolic enhancement effect.

Piracetam is a good example but all the racetams are disappointingly weak. Fasoracetam is an exception, it seems to modulate glutamate receptors somehow (people parrot that it upregulates GABAB but I'm not convinced that works). It gives an effect that sometimes lasts several days (a little like 5a-DHP does). I wish more was known about it.

 

[Terma]

Worth saying Inosine had a good effect, but it aggravated all my joint problems.

 

[Arrade]

Good diet and exercise and you wouldn’t get any problems

 

[Wolf]

In the past I have had good luck with Piracetam taken in the long term. As far as actual increases in ability to do a certain task or learn go, practice makes perfect.