Nootropics (// noh-ə-TROP-iks) (colloquial: smart drugs and cognitive enhancers) are drugs, supplements, and other substances that may improve cognitive function, particularly executive functions, memory, creativity, or motivation, in healthy individuals. While many substances are purported to improve cognition, research is at a preliminary stage as of 2018, and the effects of the majority of these agents are not fully determined.
The use of cognition-enhancing drugs by healthy individuals in the absence of a medical indication spans numerous controversial issues, including the ethics and fairness of their use, concerns over adverse effects, and the diversion of prescription drugs for nonmedical uses, among others. Nonetheless, the international sales of cognition-enhancing supplements exceeded US$1 billion in 2015 when global demand for these compounds grew.
The word nootropic was coined in 1972 by a Romanian psychologist and chemist, Corneliu E. Giurgea, from the Greek words νοῦς (nous), or "mind", and τρέπειν (trepein), meaning to bend or turn.
Availability and prevalence
In 2008, the most commonly used class of drug was stimulants, such as caffeine. Manufacturer's marketing claims for dietary supplements are usually not formally tested and verified by independent entities.
Use by students
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 lifetime. 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 intended for performance enhancement 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.
The main concern with pharmaceutical drugs is adverse effects, which also apply to nootropics with undefined effects. Long-term safety evidence is typically unavailable for nootropics. Racetams — piracetam and other compounds that are structurally related to piracetam — have few serious adverse effects and low toxicity, but there is little evidence that they enhance cognition in people having no cognitive impairments.
In the United States, dietary supplements may be marketed if the manufacturer can show that the supplement is generally recognized as safe, and if the manufacturer does not make any claims about using the supplement to treat or prevent any disease or condition; supplements that contain drugs or advertise health claims are illegal under US law.
Central nervous system stimulants 
Systematic reviews and meta-analyses of clinical research in humans established that certain central nervous system stimulants, when taken at low doses, enhanced cognition in healthy people; in particular, the classes of stimulants that demonstrated cognition-enhancing effects in humans act as direct agonists or indirect agonists of dopamine receptor D1, adrenoceptor A2, or both types of receptor in the prefrontal cortex. Relatively high doses of stimulants caused cognitive deficits.
A 2014 systematic review noted that low doses of amphetamine also improved memory consolidation, in turn leading to improved recall of information in non-ADHD youth. It also improved task saliency (motivation to perform a task) and performance on tedious tasks that required a high degree of effort.
- Methylphenidate – a benzylpiperidine that had cognitive effects (e.g., working memory, episodic memory, and inhibitory control, aspects of attention, and planning latency) in healthy people. It also may improve task saliency and performance on tedious tasks. At above optimal doses, methylphenidate had off–target effects that decreased learning.
- Eugeroics (armodafinil and modafinil) – are classified as "wakefulness promoting" agents; modafinil increased alertness, particularly in sleep deprived individuals, and was noted to facilitate reasoning and problem solving in non-ADHD youth. Modafinil did not produce improvements in mood, memory, and motivation in sleep deprived or non-sleep deprived individuals.
- Xanthines (most notably, caffeine) – were shown in a 2007 study to increase alertness, performance, and, in some studies, memory. Children and adults who consumed low doses of caffeine showed increased alertness, yet a higher dose was needed to improve performance.
- Nicotine – A meta-analysis of 41 preliminary human studies concluded that nicotine or smoking caused small improvements in fine motor abilities, alerting and orienting attention, and episodic and working memory.
Racetams, such as piracetam, oxiracetam, and aniracetam, which are often marketed as cognitive enhancers and sold over-the-counter. Racetams are often referred to as nootropics, but this property is not well established. The racetams have poorly understood mechanisms, although piracetam and aniracetam are known to act as positive allosteric modulators of AMPA receptors and appear to modulate cholinergic systems.
According to the US Food and Drug Administration, "Piracetam is not a vitamin, mineral, amino acid, herb or other botanical, or dietary substance for use by man to supplement the diet by increasing the total dietary intake. Further, piracetam is not a concentrate, metabolite, constituent, extract or combination of any such dietary ingredient. [...] Accordingly, these products are drugs, under section 201(g)(1)(C) of the Act, 21 U.S.C. § 321(g)(1)(C), because they are not foods and they are intended to affect the structure or any function of the body. Moreover, these products are new drugs as defined by section 201(p) of the Act, 21 U.S.C. § 321(p), because they are not generally recognized as safe and effective for use under the conditions prescribed, recommended, or suggested in their labeling."
- L-Theanine – A 2014 systematic review and meta-analysis found that concurrent caffeine and L-theanine use had synergistic psychoactive effects that promoted alertness, attention, and task switching; these effects were most pronounced during the first hour post-dose. However, the European Food Safety Authority reported that, when L-theanine is used by itself (i.e. without caffeine), there is insufficient information to determine if these effects exist.
- Tolcapone – a systematic review noted that it improved verbal episodic memory and episodic memory encoding.
- Levodopa – a systematic review noted that it improved verbal episodic memory and episodic memory encoding.
- Atomoxetine – may improve working memory and attention when used at certain doses.
- Panax ginseng – A review by the Cochrane Collaboration concluded that "there is a lack of convincing evidence to show a cognitive enhancing effect of Panax ginseng in healthy participants and no high quality evidence about its efficacy in patients with dementia." According to the National Center for Complementary and Integrative Health, "[a]lthough Asian ginseng has been widely studied for a variety of uses, research results to date do not conclusively support health claims associated with the herb."
- Ginkgo biloba – An extract of Ginkgo biloba leaf is marketed in dietary supplement form with claims it can enhance cognitive function in people without known cognitive problems, although there is no high-quality evidence to support such effects on memory or attention in healthy people.
- Salvia officinalis (sage) – Some research has suggested certain extracts of Salvia officinalis may have positive effects on human brain function, but due to significant methodological problems, no firm conclusions can be drawn. The thujone present in Salvia extracts may be neurotoxic.
Null findings in systematic reviews
- Omega-3 fatty acids: DHA and EPA – two Cochrane Collaboration reviews on the use of supplemental omega-3 fatty acids for ADHD and learning disorders conclude that there is limited evidence of treatment benefits for either disorder. Two other systematic reviews noted no cognition-enhancing effects in the general population or middle-aged and older adults.
- Folate – no cognition-enhancing effects in middle-aged and older adults.
- Vitamin B6 – no cognition-enhancing effects in middle-aged and older adults.
- Vitamin B12 – no cognition-enhancing effects in middle-aged and older adults.
- Vitamin E – no cognition-enhancing effects in middle-aged and older adults.
- Pramipexole – no significant cognition-enhancing effects in healthy individuals.
- Guanfacine – no significant cognition-enhancing effects in healthy individuals.
- Clonidine – no significant cognition-enhancing effects in healthy individuals.
- Fexofenadine – no significant cognition-enhancing effects in healthy individuals.
- Cognitive science
- Human enhancement
- List of drugs used by militaries
- Neurobiological effects of physical exercise § Cognitive control and memory
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