Noopept self-experiment: no effects

You're completely ignoring the complex pharmacodynamics of noopept. Of course high oral doses are going to lead to more side effects, with less of the wanted effects. That is because the metabolites are still active, but in different ways. You want to get the full structure across the BBB BEFORE is gets broken apart, or the PGP structure is not going to exert its nootropic effect. That is the key to making nooept work.

There also seems to be no particular consensus in the anecdotes on /r/nootropics[1] about sublingual being all-important.

Why are you suddenly placing weight on anecdotes, when there is evidence for the pharmacodynamic issues?

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Oral administration of noopept reaches much lower plasma concentrations than IV and sublingual. A lot of people quote a Russian study as saying that it's oral bioavailability is 97%, but that is incorrect.

The study showing that is in Russian and was done on rats and chinchilla rabbits. Their finding was actually 98.67% bioaccessibility of oral tablets in comparison to the oral parent compound via a feeding tube. The actual finding of peroral in comparison to IV was 9.33%. That means that only roughly 10% of the oral dose makes it to your bloodstream. Those quoting the 97% number have not read the actual study. I'll link the full text for you below.

Full Text

> The absolute bioaccessibility was on the average
AUC
p.o./

AUC
i.v.
= 9.33  +-1.30%, which is evidence of a pronounced effect of the “first passage” via the gastrointestinal
tract and the liver. In comparison with rats, rabbits are characterized by slower absorption of the parent substance,
which is manifested by an almost twofold increase in MRT
and by decrease in the C
max

AUC
0  
ratio in the latter case.

Peptides are easily ripped apart by digestive enzymes, and noopept is not immune to these effects. It's only saving grace is that it is a very small dipeptide. This means that it has a higher likelihood of being absorbed before being ripped apart than larger peptides that are almost 0% bioavailable. The longer it takes to get to your bloodstream, the more it will be broken apart. It will be ripped into it's 3 parts, the glycine, proline, and phenylacetyl esters. If this happens peripherally, the molecules are useless to the brain. They must pass the BBB before being metabolized. This is much less likely if you allow it to undergo first pass metabolism. The only thing noopept has going for it is size, which as you can see from the study doesn't help much.

Noopept is active orally, but much less than sublingual. Even the Russian pharmaceutical instructions state that it should be taken sublingually. The study I linked used 10mg/kg IV, and 50mg/kg peroral, and still the oral was unable to get close to the Cmax of IV.

>Thus, the results of our investigation showed that the absolute (peroral) bioaccessibility of noopept is 7.09% in rats and
9.33%  +-1.30% in rabbits.

Here is another Russian study on the matter:

Similar plasma level of GVS- 111 was observed after 5 mg/kg parenteral and 50 mg/kg oral administration.

So it took 50mg/kg peroral to reach the plasma concentration of 5mg/kg paenteral. A very substantial difference.

Considerable differences related to the administration route were revealed in GVS-111 metabolism. After parenteral administration, apart from the unchanged GVS-111 molecule, the plasma contained 2 phenylacetyl metabolites phenylacetylproline and phenylacetic acid, which were not detected after oral administration. At the same time, plasma chromatograms after oral administration showed a peak which was eluted before GVS-111 and differed from the known phenylacetyl-derivatives by the elution time. It could be either hydroxylated or methylated GVS-111 metabolite. This difference in GVS-111 metabolism in different administration routes seems to be due to the fact that parenterally administered peptide is hydrolyzed preferentially by plasma peptidases, while metabolic transformations after oral administration occur during its first passage through the liver.

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So taking noopept orally is going to lead to high levels of the metabolites glycine, proline, and phenylacetyl esters. What it will not do is get the coveted proline-glycine-proline structure to the brain in meaningful amounts. That PGP structure is what we want, and is what leads to both Selank's and Semax's nootropic effects. So taking larger doses of noopept orally would be similar to taking huge doses of Selank and Semax orally. It does not make any sense.

Again, I am not trying to impress anyone with observations. I am simply stating that any peptide is going to be EXTREMELY dependent on route of administration. Your test results sublingually could show the exact same results. I am not saying that is not a possibility. But that should be accounted for in your study design.