It doesn't help that I'm on Adderall, but if left to my own devices, would absolutely skip it. I'm assuming I benefit in the able to think way from it. Largely the only reason I know I missed a dose is if I find I lose my patience quickly with others.
That, historically, does not work well for neurochemistry. Large random trials are good for an average biological response of profitable chemicals, but it seems there are significant differences in neurochemistry, between people, that these don't capture. If you've ever had a prescription for most anything mental related, like ADHD, depression, etc, there's never just one drug, there's a panel that you just kinda go through until one works for your personal neurochemistry, with some having detrimental side effects for some people.
Unsurprisingly, it seems to be the same with many of these nootropics. I've had several very negative reactions to common nootropics at fractional doses, where others have positive experiences at many times the dose. A few resulted in migraines every day I took it, until I stopped, with one quickly resulting in depression and the only suicidal thoughts of my life, which went aways just as fast as I stopped. One hurt my short term memory so much I couldn't repeat a phone number (a very potent racetam like).
Some nootropics are precursors, which are mostly self regulating/supplements, but there are many out there that very actively poke low level neurochemicals, and your personal response will vary, just as is expected in the regulated drug world.
Min/maxing personal neurochemistry won't come from large random trials.
Controlled trials are actually very revealing of the placebo effect, which is a rampant confounded in nootropics communities. When people spend months reading about new nootropics, then a week waiting for it in the mail, then they take their first dose with excitement and anticipation they generally report feeling something.
The nice thing about trials is that they can start separating out this placebo effect.
Several people have done self-trials with different compounds with surprising results. Gwern is perhaps the most famous. Whenever people post about magnesium being a life altering substance or producing profound effects I also point them to his measured magnesium trials where the net effect over time was beginning to trend negative.
One of the myths in nootropics communities is that everything is a matter of neurochemistry and everyone is substantially different. In reality, RCTs are actually great at capturing enough people to see subgroups responding if you have enough people.
One thing most nootropics people don’t acknowledge enough is how often placebo effect appears in RCTs. Perform an RCT for depression and the placebo group will get better. It happens in every study. Give college students Adderall before an exam and they will report performing better, despite no statistical improvement in their grades. Now consider these facts in light of all of the scattered nootropics forum reports from people claiming different substances cured their depression or made them smarter. Not surprisingly, if you check their post history more recent comments will show them off on a new tangent trying a new substance, the old one long forgotten as a short trial that didn’t work out.