Bad first Aniracetam experience. Never touch again or try different combinations?

I believe the rationale behind the MN blend was that adding a cerebral vasodilator would warrant a lower dose of Aniracetam than the standard 750 mg, since the resulting vasodilatation would bring more Ani to the brain. It does make sense logically however I'm unsure of whether or not there are any studies to back up this idea.

I don't see any reason why that would be the case. Aniracetam's issue is rapid and total first-pass metabolism in the liver. Inhibiting that would help, but vasodilation is not going to really cause more to reach the brain.

I agree, if there's any consensus on nootropics, it's that high interindividual variability is a frustrating part of the experience and as such it's hard to rely on other people's advice. On top of that, you've also got intraindividual variability "This bacopa extract doesn't work for you? Try the other half dozen extracts out there".

Intraindividual variability in drug response is a big issue across the board. It's just that most doctors don't really discuss it or understand it, and our schooling doesn't really inform people properly. Everyone thinks that X drug is prescribed for something, so everyone will get the effects desired. It creates a notion of certainty that is not really based in reality.

The old school of thought a few years back was the responders to fat-soluble racetams are non-responders to water-soluble racetams and vice-versa. Most likely backed up by anecdotal evidence, but interesting nonetheless. I've got some Piracetam on the way from ND as well, and as I know I've tolerated it well in the past, I'll focus on that.

I don't see why that would be, either. Most people completely misunderstand solubility. Things can be water and lipid soluble at the same time. In fact, the most bioavailable things are both water and lipid soluble. You have an ideal range with a compound's LogP. One of the Lapinsky Rules of Five is that for a compound to be very bioavailable, it needs a LogP under 5. Another is that it should have a molecular weight below 500 Daltons. One of my team wrote a pretty good blog on CoQ10 that touches on that.

http://nootropicsdepot.com/articles/coenzyme-q10-superior-coq10-supplement-over-grocery-store-brands/

Pramiractam is both water and lipid soluble, with its ACD LogP (Fragment LogP) being -1.4 and its ALogP (Atomic LogP) being 0.49. It has functional groups that are both hydrophilic and lipophilic. Piracetam is very polar, with its LogP being -1.18, -1.39, or -1.75 depending on how you calculate it. So it is primarily water soluble. Aniracetam has a LogP of 1.11 or 1.35, which makes it primarily lipid soluble. So it is right in the ideal range for bioavailability, which is why it is rapidly and completely absorbed in the GI tract. Aniracetam is just immediately metabolized into N-anisoyl-GABA, P-Anisic Acid, and 2-pyrrolidinone. Piracetam is not metabolized in any meaningful amounts. Piracetam also has a unique binding site on the AMPA receptors that differs from the other racetams. There is also protein binding that comes into play. Piracetam has very little protein binding. So you don't really have it build up in the body. Aniracetam is metabolized too quickly to have protein binding. However, pramiracetam has extensive protein binding. So it is widely distributed in tissues around the body and reaches steady state plasma levels after 24-48 hours of chronic dosing. So you can see the differences in just the racetams is pretty extensive. It's no wonder why there is variability in responses between them.

How do you like the piracetam so far?