Nootropics (// noh-ə-TROP-iks), also referred to as smart drugs, memory enhancers, neuro enhancers, cognitive enhancers, and intelligence enhancers, are drugs, supplements, nutraceuticals, and functional foods that improve one or more aspects of mental function, such as working memory, motivation, and attention. The word nootropic was coined in 1972 by the Romanian Dr. Corneliu E. Giurgea, derived from the Greek words νους nous, or "mind," and τρέπειν trepein meaning to bend or turn.
Availability and prevalence
At present, there are only a few drugs which have been shown to improve some aspect of cognition in medical reviews. Many more are in different stages of development. The most commonly used class of drug is stimulants.
These drugs are used primarily to treat people with cognitive or motor function difficulties attributable to such disorders as Alzheimer's disease, Parkinson's disease, Huntington's disease and ADHD. However, more widespread use is being recommended by some researchers. Many drugs are marketed heavily on the Internet as having a variety of human enhancement applications as well. Nevertheless, intense marketing may not correlate with efficacy; while scientific studies support the beneficial effects of some compounds, the marketing claims by manufacturers of over-the-counter products are not formally tested.
In academia, modafinil has been used to increase productivity, although its long-term effects have not been assessed in healthy individuals. Stimulants such as dimethylamylamine and methylphenidate are used on college campuses and by younger groups. One survey found that 7% of students had used stimulants for a cognitive edge, and on some campuses use in the past year is as high as 25%. The use of prescription stimulants is especially prevalent among students attending academically competitive colleges and students who are members of a fraternity or sorority.
Several factors positively and negatively influence the use of drugs to increase cognitive performance. Among them are personal characteristics, drug characteristics, and characteristics of the social context.
The main concern with pharmaceutical drugs is adverse effects, and these concerns apply to cognitive-enhancing drugs as well. Cognitive enhancers are often taken for the long-term when little data is available. While certain racetam compounds are suspected to have nootropic qualities, few side-effects, and a wide therapeutic window (low overdose risk), other cognitive enhancers may be associated with a high incidence of adverse effects or a narrower therapeutic window (higher overdose risk). While addiction to stimulants is sometimes asserted to be a cause for concern, a very large body of research on the therapeutic use of the "more addictive" psychostimulants indicate that addiction is fairly rare in therapeutic doses.
Certain stimulants will enhance cognition in the general population, but only when used at low (therapeutic) concentrations. Relatively high doses of stimulants will result in cognitive deficits.
- Anti-ADHD agents
- Amphetamine pharmaceuticals (Adderall, dextroamphetamine, and lisdexamfetamine [a prodrug]) – TAAR1 agonists that mimic the effect of endogenous phenethylamine. Benefits in cognitive control and working memory are evident in the general population, and especially in individuals with ADHD. It also improves performance on tedious tasks that require a high degree of effort.
- Methylphenidate – a substituted phenethylamine that improves working memory and cognitive control. It also improves performance on tedious tasks that require a high degree of effort. At above optimal doses, methylphenidate has offtarget effects that can decrease learning by activating neurons not involved in the task at hand.
- Eugeroics – wakefulness promoting agents; increase alertness, particularly in sleep deprived individuals. They are clinically prescribed for narcolepsy, shift work sleep disorder, and daytime sleepiness remaining after sleep apnea treatments.
- Xanthines – most notably, Caffeine – shown to increase alertness, performance, and in some studies, memory. Children and adults who consume low doses of caffeine showed increase alertness, yet a higher dose was needed to improve performance.
- Nicotine – A meta-analysis of 41 double-blind, placebo-controlled studies concluded that nicotine or smoking had significant positive effects on aspects of fine motor abilities, alerting and orienting attention, and episodic and working memory.
- Phosphatidylserine (a phospholipid) with DHA and EPA (omega-3 fatty acids) – A review of literature and subsequent randomized controlled trial indicate concurrent supplemental use can protect and potentially improve brain function, with clinical benefits for those with ADHD and other disorders. Two Cochrane Collaboration reviews on the use of supplemental omega-3 fatty acids alone (without phosphatidylserine) for ADHD and learning disorders conclude that there is limited evidence of treatment benefits for either disorder.
- Selegiline and rasagiline – Monoamine oxidase B inhibitors with neuroprotective properties, especially for those with Parkinson's disease.
- Tianeptine – Tianeptine prevents stress-induced dendritic remodeling in various brain structures, enhances several metrics of cognition in animal models, and antagonizes alcohol's neurodegenerative effects.
- Valproate – a study has suggested that Valproate may be able to enhance the cognitive ability of absolute pitch 
- Bacopa monnieri – A neutraceutical herb with "neural tonic" and memory enhancing properties shown in humans in a double-blinded RCTs.
- Panax ginseng – Multiple RCTs in healthy volunteers have indicated increases in accuracy of memory, speed in performing attention tasks and improvement in performing difficult mental arithmetic tasks, as well as reduction in fatigue and improvement in mood.
- Ginkgo Biloba – A meta-analysis of 29 RCTs stated "there is consistent evidence that chronic administration improves selective attention, some executive processes and long-term memory for verbal and non-verbal material."
- Melissa officinalis
- Epigallocatechin gallate
- St John's Wort – Anti-inflammatory, antibiotic, and neuroprotective antidepressant compound which has extremely low toxicity.
- Isoflavones – A double-blind, placebo-controlled study showed improvement in spatial working memory after administration of isoflavones. One RCT showed soy isoflavone supplementation improved performance on 6 of 11 cognitive tests, including visual-spatial memory and construction, verbal fluency and speeded dexterity, but worse on two tests of executive function.
The racetams are structurally similar compounds, such as pramiracetam, oxiracetam, coluracetam, and aniracetam, which are often marketed as cognitive enhancers and sold over-the-counter. Racetams are often referred to as nootropics, but this property of the drug class is not well established. The racetams have a poorly understood mechanisms of action; however, piracetam and aniracetam are known to act as positive allosteric modulators of AMPA receptors and appear to modulate cholinergic systems.
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