Cognitive Enhancers: Mechanisms and Tradeoffs

[Epistemic status: so, so, so speculative. I do not necessarily endorse taking any of the substances mentioned in this post.]

There’s been recent interest in “smart drugs” said to enhance learning and memory. For example, from the Washington Post:

When aficionados talk about nootropics, they usually refer to substances that have supposedly few side effects and low toxicity. Most often they mean piracetam, which Giurgea first synthesized in 1964 and which is approved for therapeutic use in dozens of countries for use in adults and the elderly. Not so in the United States, however, where officially it can be sold only for research purposes. Piracetam is well studied and is credited by its users with boosting their memory, sharpening their focus, heightening their immune system, even bettering their personalities.

Along with piracetam, a few other substances have been credited with these kinds of benefits, including some old friends:

“To my knowledge, nicotine is the most reliable cognitive enhancer that we currently have, bizarrely,” said Jennifer Rusted, professor of experimental psychology at Sussex University in Britain when we spoke. “The cognitive-enhancing effects of nicotine in a normal population are more robust than you get with any other agent. With Provigil, for instance, the evidence for cognitive benefits is nowhere near as strong as it is for nicotine.”

But why should there be smart drugs? Popular metaphors speak of drugs fitting into receptors like “a key into a lock” to “flip a switch”. But why should there be a locked switch in the brain to shift from THINK WORSE to THINK BETTER? Why not just always stay on the THINK BETTER side? Wouldn’t we expect some kind of tradeoff?

Piracetam and nicotine have something in common: both activate the brain’s acetylcholine system. So do three of the most successful Alzheimers drugs: donepezil, rivastigmine, and galantamine. What is acetylcholine and why does activating it improve memory and cognition?