We understand that cognitive-enhancing substances such as nicotine, caffeine, amphetamine, modafinil... induce clear improvements in an acute dose, but that's not what we want. We want to know that it works with chronic doses and induces effectively a permanent improvement in cognitive ability.

Do their effects wear off as you develop a tolerance? Can you actually use these therapeutically? Do their effects wear off if you cease their use? For example, I see a study on nicotine in rats improving their working memory even two weeks after ceasing a 12mg/kg/day for 21+ days dose, but that dose is extreme, and they appear to say that the "lower" dose of 5mg/kg/day did not induce these persistent improvements. From what I've read, typical doses are miniscule in comparison, only maybe 0.33mg per hour in humans, according to a 7mg transdermal patch, and even the highest doses are maybe 55mg, or 2mg per hour.

Do we have any proper information on this topic? We all know that acute doses in people who have never used the substance induces obvious benefits to intelligence, but can we use these therapeutically for a lasting benefit, or do we develop a tolerance and lose these benefits? Withdrawal induces impairment, but has their chronic use given them a permanent increased ability beyond their former self having never used the drug?