Nootropics (English pronunciation: /noʊ.əˈtrɒpɪks/
noh-ə-TROP-iks), also known as smart drugs and cognitive enhancers,
are drugs, supplements, and other substances that improve cognitive
function, particularly executive functions, memory, creativity, or
motivation, in healthy individuals.
The use of cognition-enhancing drugs by healthy individuals in the
absence of a medical indication is one of the most debated topics
among neuroscientists, psychiatrists, and physicians which spans a
number of 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 and the global demand for these compounds is still
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
1 Availability and prevalence
1.1 Use by students
2 Side effects
Central nervous system
Central nervous system stimulants
4 Dietary supplements
5 Null findings in systematic reviews
6 See also
8 External links
Availability and prevalence
There are only a few drugs that are known to improve some aspect of
cognition. Many more are in different stages of development. The
most commonly used class of drug is stimulants, such as caffeine.
These drugs are purportedly used primarily to treat cognitive or motor
function difficulties attributable to disorders such as Alzheimer's
disease, Parkinson's disease, Huntington's disease, and ADHD.[citation
needed] Some researchers, however, report more widespread use despite
concern for further research. Nevertheless, intense marketing may
not correlate with efficacy. While scientific studies support the
beneficial effects of some compounds, 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 attending academically competitive colleges. 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 used for performance enhancement
rather than as recreational drugs.
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
The main concern with pharmaceutical drugs is adverse effects, and
these concerns apply to cognitive-enhancing drugs as well. Long-term
safety data is typically unavailable for some types of nootropics
(e.g., many non-pharmaceutical cognitive enhancers, newly developed
pharmaceuticals and pharmaceuticals with short-term therapeutic use).
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 individuals
without cognitive impairments.
While addiction to stimulants is sometimes identified as 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. On their safety profile,
a systematic review from June 2015 asserted, "evidence indicates that
at low, clinically relevant doses, psychostimulants are devoid of the
behavioral and neurochemical actions that define this class of drugs
and instead act largely as cognitive enhancers."
In the United States dietary supplements may be marketed if the
manufacturer can show that it can manufacture the supplement safely,
that the supplement is indeed generally recognized as safe, and if the
manufacturer does not make any claims about the supplement's use to
treat or prevent any disease or condition; supplements that contain
drugs or for which treatment or prevention claims are made are illegal
under US law.
Central nervous system
Central nervous system stimulants 
See also: Yerkes–Dodson law
Hebbian version of the Yerkes–Dodson law
In 2015, systematic medical reviews and meta-analyses of clinical
research in humans established consensus that certain central nervous
system stimulants, only when used at low (therapeutic) concentrations,
unambiguously enhance cognition in the general
population; in particular, the classes of stimulants
that demonstrate cognition-enhancing effects in humans act as direct
agonists or indirect agonists of dopamine receptor D1, adrenoceptor
A2, or both receptors in the prefrontal cortex.
Relatively high doses of stimulants cause cognitive deficits.
Amphetamine (e.g., dextroamphetamine (enantiopure drug),
lisdexamfetamine [an inactive prodrug]), methamphetamine (a
substituted amphetamine) – systematic reviews and
meta-analyses report that amphetamine benefits a range of cognitive
functions (e.g., inhibitory control, episodic memory, working memory,
and aspects of attention) in the general population, and these effects
are especially notable in individuals with ADHD. A
systematic review from 2014 noted that low doses of amphetamine also
improve memory consolidation, in turn leading to improved recall of
information in non-
ADHD youth. It also improves task saliency
(motivation to perform a task) and performance on tedious tasks that
require a high degree of effort.
Methylphenidate – a
Benzylpiperidine that improves a range of
cognitive functions (e.g., working memory, episodic memory, and
inhibitory control, aspects of attention, and planning latency) in the
general population. It also improves task saliency and
performance on tedious tasks that require a high degree of effort.
At above optimal doses, methylphenidate has off target effects that
can decrease learning by activating neurons not involved in the task
Eugeroics (armodafinil and modafinil) – wakefulness promoting
agents; modafinil increases alertness, particularly in sleep deprived
individuals, and was noted to facilitate reasoning and problem solving
in a systematic review. 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 increased
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.
A 2015 review noted that stimulation of the α4β2 nicotinic receptor
is responsible for certain improvements in attentional
performance; among the nicotinic receptor subtypes, nicotine has
the highest binding affinity at the α4β2 receptor (ki=1 nM),
which is also the biological target that mediates nicotine's addictive
Main article: Racetams
Racetams, such as piracetam, oxiracetam, and aniracetam, are
structurally similar compounds, 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 poorly understood mechanisms of
action; however, piracetam and aniracetam are known to act as positive
allosteric modulators of AMPA receptors and appear to modulate
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
L-Theanine – A 2014 systematic review and meta-analysis found
that concurrent caffeine and
L-theanine use has synergistic
psychoactive effects that promote alertness, attention, and task
switching; these effects are most pronounced during the first hour
post-dose. However, the
European Food Safety Authority
European Food Safety Authority reports
L-theanine is used by itself (i.e. without caffeine) there
is insufficient information to determine if positive health effects
Tolcapone – a systematic review noted that it improves verbal
episodic memory and episodic memory encoding.
Levodopa – a systematic review noted that it improves verbal
episodic memory and episodic memory encoding.
Atomoxetine – can improve working memory and aspects of
attention when used at an optimal dose.
Bacopa monnieri – A herb sold as a dietary supplement. There
is some preliminary evidence for memory-enhancing effects.
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." According to a
review published in the journal "Advances in Nutrition", 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 – An extract of
Ginkgo biloba leaf (GBE) is
marketed in dietary supplement form with claims it can enhance
cognitive function in people without known cognitive problems. Studies
have failed to find such effects on memory or attention in healthy
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
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
Vitamin B6 – no cognition-enhancing effects in middle-aged and
Vitamin B12 – no cognition-enhancing effects in middle-aged
and older adults.
Vitamin E – no cognition-enhancing effects in middle-aged and
Pramipexole – no significant cognition-enhancing effects in
Guanfacine – no significant cognition-enhancing effects in
Clonidine – no significant cognition-enhancing effects in
Ampakines – no significant cognition-enhancing effects in
Fexofenadine – no significant cognition-enhancing effects in
Salvia officinalis – Although some evidence is suggestive of
cognition benefits, the study quality is so poor that no conclusions
can be drawn from it.
List of drugs used by militaries
Neurobiological effects of physical exercise § Cognitive control
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tasks. However, they do confirm the reality of cognitive enhancing
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Methylphenidate appears to
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• Negative results were found for pramipexole, guanfacine,
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Unfortunately, promising beneficial effects showed in clinical studies
are debased by methodological issues
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