Nootropics communities like to wave these details away because they like positive results and think that the drugs simply increase cognition, but that’s rarely true.

The #2 entry in the list is the perfect example of this: Acetylcholinesterase inhibitors can show positive effects in disease states like Parkinson’s (where dopaminergic neurons are destroyed, resulting in specific imbalances) but they are known to induce depression in healthy volunteers. Confusingly, they can cause feelings of positive effect early on before the depression sets in for some people. This leads to an all too common scenario on nootropics forums where someone suffers from depression for months or years before realizing that their supplement stack containing cholinergic substances is making it worse. Some times people don’t realize this until they accidentally run out and start feeling better after a few days of not taking their supplements.

1) many substances are drugs, others foods and others natural elements. Nootropic is such a wide term

2) non-blindness is a major source of error. Mental function has a huge error bars with many causal factors and nonsensitive measurement methods

3) such "meta-analyses" are typically performed by experts in the field. But you are also a kind of supplement expert after "many years on /r/nootropics"

4) the champions (amphetamines and AChE inhibitors) are of no surprise. They have so vast and widespread effects that are more drugs than mere -tropics

5) as a neurologist I can see some clinical relevance of your work. By prescribing something some benefit is offered but more confusion is caused from which one is better.

Its hard to track your mesh search terms, but looks like you are searching for improvement AND a lot of other search terms. Aren't you filtering out any articles which show deterioration?

I think a meta analysis is probably what you are actually looking for. It would be better, I think, to read some of these and manually include relevant references.

Neither of your assumptions are true.

I don't think pharmaceuticals qualify as nootropics as they're never without meaningful adverse effects. The safety profile is more important than the effect profile.