When Giurgea coined the word nootropic (combining the Greek words for mind and bending) in the 1970s, he was focused on a drug he had synthesized called piracetam. Although it is approved in many countries, it isn’t categorized as a prescription drug in the United States. That means it can be purchased online, along with a number of newer formulations in the same drug family (including aniracetam, phenylpiracetam, and oxiracetam). Some studies have shown beneficial effects, including one in the 1990s that indicated possible improvement in the hippocampal membranes in Alzheimer’s patients. But long-term studies haven’t yet borne out the hype.
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. But it’s only one of many formulations in the racetam drug family. Newer ones include aniracetam, phenylpiracetam and oxiracetam. All are available online, where their efficacy and safety are debated and reviewed on message boards and in podcasts.
One should note the serious caveats here: it is a small in vitro study of a single category of human cells with an effect size that is not clear on a protein which feeds into who-knows-what pathways. It is not a result in a whole organism on any clinically meaningful endpoint, even if we take it at face-value (many results never replicate). A look at followup work citing Rapuri et al 2007 is not encouraging: Google Scholar lists no human studies of any kind, much less high-quality studies like RCTs; just some rat followups on the calcium effect. This is not to say Rapuri et al 2007 is a bad study, just that it doesn’t bear the weight people are putting on it: if you enjoy caffeine, this is close to zero evidence that you should reduce or drop caffeine consumption; if you’re taking too much caffeine, you already have plenty of reasons to reduce; if you’re drinking lots of coffee, you already have plenty of reasons to switch to tea; etc.
Government restrictions and difficulty getting approval for various medical devices is expected to impede market growth. The stringency of approval by regulatory authorities is accompanied by the high cost of smart pills to challenge the growth of the smart pills market. However, the demand for speedy diagnosis, and improving reimbursement policies are likely to reveal market opportunities.
It is a known fact that cognitive decline is often linked to aging. It may not be as visible as skin aging, but the brain does in fact age. Often, cognitive decline is not noticeable because it could be as mild as forgetting names of people. However, research has shown that even in healthy adults, cognitive decline can start as early as in the late twenties or early thirties.
Brain-imaging studies are consistent with the existence of small effects that are not reliably captured by the behavioral paradigms of the literature reviewed here. Typically with executive function tasks, reduced activation of task-relevant areas is associated with better performance and is interpreted as an indication of higher neural efficiency (e.g., Haier, Siegel, Tang, Abel, & Buchsbaum, 1992). Several imaging studies showed effects of stimulants on task-related activation while failing to find effects on cognitive performance. Although changes in brain activation do not necessarily imply functional cognitive changes, they are certainly suggestive and may well be more sensitive than behavioral measures. Evidence of this comes from a study of COMT variation and executive function. Egan and colleagues (2001) found a genetic effect on executive function in an fMRI study with sample sizes as small as 11 but did not find behavioral effects in these samples. The genetic effect on behavior was demonstrated in a separate study with over a hundred participants. In sum, d-AMP and MPH measurably affect the activation of task-relevant brain regions when participants’ task performance does not differ. This is consistent with the hypothesis (although by no means positive proof) that stimulants exert a true cognitive-enhancing effect that is simply too small to be detected in many studies.
But 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.
Table 5 lists the results of 16 tasks from 13 articles on the effects of d-AMP or MPH on cognitive control. One of the simplest tasks used to study cognitive control is the go/no-go task. Subjects are instructed to press a button as quickly as possible for one stimulus or class of stimuli (go) and to refrain from pressing for another stimulus or class of stimuli (no go). De Wit et al. (2002) used a version of this task to measure the effects of d-AMP on subjects’ ability to inhibit a response and found enhancement in the form of decreased false alarms (responses to no-go stimuli) and increased speed of correct go responses. They also found that subjects who made the most errors on placebo experienced the greatest enhancement from the drug.
The use of prescription stimulants is especially prevalent among students. Surveys suggest that 0.7–4.5% of German students have used cognitive enhancers in their lifetimes. Stimulants such as dimethylamylamine and methylphenidate are used on college campuses and by younger groups. Based upon studies of self-reported illicit stimulant use, 5–35% of college students use diverted ADHD stimulants, which are primarily used for enhancement of academic performance rather than as recreational drugs. Several factors positively and negatively influence an individual's willingness to use a drug for the purpose of enhancing cognitive performance. Among them are personal characteristics, drug characteristics, and characteristics of the social context.