Nootropic
From Wikipedia, the free encyclopedia
From Wikipedia, the free encyclopedia
Nootropics—also called smart drugs and cognitive
enhancers—are drugs, supplements, or 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 growing rapidly.
The word nootropic was coined in 1972 by a Romanian
psychologist and chemist, Corneliu E. Giurgea,from the Greek words νους nous,
or "mind", and τρέπειν trepein meaning to bend or turn.
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. 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.
Academic use
In academia, nootropics have been used to increase
productivity, despite their long-term effects lacking conclusive research in
healthy individuals. 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 social
context.
Side effects
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—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 supplements 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.
Drugs
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 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
pharmaceuticals (Adderall, dextroamphetamine, and lisdexamfetamine [an inactive
prodrug]) – systematic reviews and meta-analyses report that amphetamine benefits
a range of aspects of cognitive control (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
substituted phenethylamine that improves cognitive control (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 at hand.
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 properties.
Miscellaneous
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.
Valproate – a study
has suggested that valproate may be able to enhance the cognitive ability of
absolute pitch.
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.
Desipramine – can
improve working memory and aspects of attention when used at an optimal dose.
Nutraceuticals
Bacopa monnieri – A
nutraceutical herb. Two review articles concluded that there is some evidence
for memory-enhancing effects, but further research is needed.
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 "Although 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 –
Different reviews come to different conclusions. A 2009 Cochrane review found
not enough evidence to make conclusions in those with dementia. A 2007
systematic review and a 2012 meta-analysis found no significant evidence
supporting cognition enhancement in healthy individuals. A 2009 review stated
"there is consistent evidence that chronic administration improves
selective attention, some executive processes and long-term memory for verbal
and non-verbal material."
Racetams
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 cholinergic systems.
According to the FDA, "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."
Negative 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.
B vitamins – no
cognition-enhancing effects in middle-aged and older adults.
Vitamin E – no
cognition-enhancing 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.
Ampakines – no
significant cognition-enhancing effects in healthy individuals.
Fexofenadine – no
significant cognition-enhancing effects in healthy individuals.
Salvia officinalis –
Although some evidence is suggestive of cognition benefits, the study quality
is so poor that no conclusions can be drawn from it.
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