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Nootropics (/noʊ.əˈtrɒpks/ 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 purportedly improve mental functions such as cognition, memory, intelligence, motivation, attention, and concentration. The word nootropic was coined in 1971 by the Romanian Dr. Corneliu E. Giurgea, derived from the Greek words νους nous, or "mind," and τρέπειν trepein meaning "to bend/turn". Nootropics are thought to work by altering the availability of the brain's supply of neurochemicals (neurotransmitters, enzymes, and hormones), by improving the brain's oxygen supply, or by stimulating nerve growth.

Availability and prevalence

At present, there are several drugs on the market that improve memory, concentration, and planning, and reduce impulsive behavior. 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. These drugs have a variety of human enhancement applications as well, and are marketed heavily on the Internet. 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.

Academic doping

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.

Surveys suggest that 3–11% of American students and 0.7–4.5% of German students have used cognitive enhancers in their lifetime.

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.

Hazards

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 known 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.

In the United States, unapproved drugs or dietary supplements do not require safety or efficacy approval before being sold.

Drugs

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Vitamins and supplements

• B Vitamins—may influence cognitive function through an effect on methylation and homocysteine levels, as excess homocysteine has been associated with cognitive impairment and the B vitamins work to reduce homocysteine. However, although epidemiological evidence shows an association, two studies did not find B vitamin supplementation improves cognitive function, and another that found an association was criticized. In 2008 a systematic review of trials found "little evidence of a beneficial impact" from supplements on cognitive function later in life. A randomized, placebo-controlled trial in 168 70 year olds with mild cognitive impairment showed that a mix of B vitamins slowed the rate of brain atrophy; the slowing was related to a decrease in homocysteine levels.

• Choline—higher concurrent choline intake was related to better cognitive performance. It improves long-term memory in animal models.

• Phosphatidylserine (a phospholipid) with DHA and EPA (omega-3 fatty acids)—concurrent supplemental use can protect and potentially improve brain function. DHA and EPA are compounds that support brain function and neurogenesis, especially during brain development. A review of literature and a more recent randomized controlled trial on supplemental phosphatidylserine with DHA and EPA indicate that there are clinical benefits for those ADHD, in addition to a range of other clinical applications. However, Cochrane Collaboration reviews on the use of supplemental omega-3 fatty acids alone (without phosphatidylserine) indicate that there is limited evidence of treatment benefits for individuals with ADHD or other learning disorders. A Norwegian study demonstrated a potential link between Omega-3 consumption during pregnancy and child intelligence test scores.

• Vitamin D—has positive effects on cardiovascular health and may have positive effects on cognitive function separately; the active form of Vitamin D seems to be involved in brain development and in adult brain function. In particular, metabolic pathways for Vitamin D in the hippocampus and cerebellum have been found. Epidemiological data show that higher Vitamin D levels (>20 ng/mL or 50 nmol/L) are associated with better cognitive function, but do not seem to be associated with better memory performance. Vitamin D has also been shown to be necessary in the production of dopamine

Stimulants

Stimulants are often seen as smart drugs, but may be more accurately termed productivity enhancers. These typically improve concentration and a few areas of cognitive performance, but only while the drug is still in the blood at therapeutic concentrations.

• Anti-ADHD agents
  • Amphetamine pharmaceuticals (Adderall, dextroamphetamine, and lisdexamfetamine )—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.
  • Methylphenidate—a substituted phenethylamine that improves working memory and cognitive control.
• Eugeroics—wakefulness promoting agents; increase alertness, particularly in sleep deprived individuals
  • Armodafinil
  • Modafinil
• Nicotine A meta-analysis of 41 double-blind, placebo-controlled studies concluded that nicotine or smoking had significant positive effects on fine motor, alerting attention-accuracy and response time (RT), orienting attention-RT, short-term episodic memory-accuracy, and working memory-RT.
• 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.

Miscellaneous

• Selegiline and rasagiline—Monoamine oxidase B inhibitors with neuroprotective properties, especially for those with Parkinson's disease
• Tianeptine—atypical antidepressant with anxiolytic properties—Tianeptine prevents stress-induced dendritic remodeling in various brain structures, enhances several metrics of cognition in animal models, and antagonizes alcohol's neurodegenerative effects.
• Bupropion—Substituted cathinone

Neutraceuticals

• 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.
• Ginko Biloba
• Melissa officinalis
• Sage
• Valerian
• Curcumin
• Epigallocatechin gallate
• St John's wort
• Isoflavones—may facilitate to cognitive function. A double-blind, placebo-controlled study showed improvement in spatial working memory after administration of an isoflavone combination containing daidzein, genistein & glycitein. In a randomized, double-blind, placebo-controlled study of older, non-demented men & women, soy isoflavone supplementation improved performance on 6 of 11 cognitive tests, including visual-spatial memory and construction, verbal fluency and speeded dexterity; unexpectedly, the placebo group performed better on 2 tests of executive function.

Racetams

This section needs more reliable medical references for verification or relies too heavily on primary sources. Please review the contents of the section and add the appropriate references if you can. Unsourced or poorly sourced material may be challenged and removed. Find sources: "Nootropic" – news · newspapers · books · scholar · JSTOR (April 2014)

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. 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.

Blood flow and metabolic function

This section needs more reliable medical references for verification or relies too heavily on primary sources. Please review the contents of the section and add the appropriate references if you can. Unsourced or poorly sourced material may be challenged and removed. Find sources: "Nootropic" – news · newspapers · books · scholar · JSTOR (April 2014)

Brain function is dependent on many basic processes such as the usage of ATP, removal of waste, and intake of new materials. Improving blood flow or altering these processes can benefit brain function. The list below contains only vasodilators that have shown at least probable mental enhancement.

• Mildronate may improve the ability of learning and memory, as the drug changes the expression of hippocampal proteins related to synaptic plasticity
• Blessed Thistle—increases blood circulation, improving memory
• Coenzyme q-10—antioxidant; increases oxygen usage by mitochondria
• Creatine—protects ATP during transport
• Lipoic acid—improves oxygen usage and antioxidant recycling, possibly improving memory
• Pyritinol—Drug similar to B vitamin Pyridoxine
• Picamilon—GABA activity and blood flow improver
• Ginkgo biloba—vasodilator. Acts as an NRI. A double-blind, placebo-controlled trial in young healthy females showed an improvement in short-term memory performance 1 hour after administration of a 600 mg dose. An analysis of 29 placebo-controlled RCTs showed that "there is consistent evidence that chronic administration improves selective attention, some executive processes and long-term memory for verbal and non-verbal material." A double-blind, placebo-controlled study in 20 young healthy volunteers showed a dose-dependent improvement in speed-of-attention following administration of 240 mg and 360 mg of Ginkgo extract, effects were measured 2.5h after administration and persisted at least until 6h; various other time- and dose-specific changes (some positive, some negative) in other areas were observed.
• Vinpocetine— is reported to have cerebral blood-flow enhancing and neuroprotective effects, and is used as a drug in Eastern Europe for the treatment of cerebrovascular disorders and age-related memory impairment. Also shown to inhibit voltage-sensitive Na+ channels—however, through a similar mechanism to reserpine, Vinpocetine may temporarily deplete the monoamines serotonin, dopamine and norepinephrine by inhibiting VMAT, thus preventing them from reaching the synapse. Vinpocetine may therefore induce or exacerbate depressive symptoms as an adverse effect. However, this effect tends to be reversible upon cessation of Vinpocetine administration, with full remission typically occurring within 3–4 weeks. Vinpocetine has been identified as a potent anti-inflammatory agent that might have a potential role in the treatment of Parkinson's disease and Alzheimer's disease.
• Vincamine—increases blood circulation (vasodilator) and metabolism in the brain; related to vinpocetine; used in sustained release.
• Nicergoline—an ergot derivative used to treat senile dementia and other disorders with vascular origins; it has been found to increase mental agility and enhance clarity and perception; it decreases vascular resistance and increases arterial blood flow in the brain, improving the utilization of oxygen and glucose by brain cells; it has been used for more than three decades for the treatment of cognitive, affective, and behavioral disorders of older people.

Nerve growth stimulation and brain cell protection

This section needs more reliable medical references for verification or relies too heavily on primary sources. Please review the contents of the section and add the appropriate references if you can. Unsourced or poorly sourced material may be challenged and removed. Find sources: "Nootropic" – news · newspapers · books · scholar · JSTOR (April 2014)

Nerves are necessary to the foundation of brain communication and their degeneracy, underperformance, or lacking can have disastrous results on brain functions. Antioxidants may prevent oxidative stress and cell death, therefore exerting a neuroprotective effect.

• Idebenone—antioxidant
• Glutathione—chief antioxidant
• Sesamol—antioxidant
• Acetylcarnitine (Acetyl-L-Carnitine Arginate or Hydrochloride)
• Inositol—implicated in memory function, deficit linked to some psychiatric illnesses—has been shown particularly efficacious in OCD patients
• Anticonvulsants—inhibit seizure related brain malfunction if a person has seizures
• Phosphatidylserine—possible membrane stabilizer
• Lion's Mane Mushroom—Stimulated myelination in an in vitro experiment and stimulated nerve growth factor in an in vitro experiment with human astrocytoma cells. Also improved cognitive ability, in a double-blind, parallel-group, placebo-controlled trial.
• SAM-e (S-Adenosyl methionine)—crucial for cellular regeneration (fuels DNA methylation), also involved with the biosynthesis of dopamine & serotonin
• Acetylcysteine (L-cysteine)—precursor to antioxidant glutathione
• Uncaria tomentosa (Cat's Claw)—in an in vitro experiment with rats, it inhibited formation of brain beta amyloid deposits, which have been associated with Alzheimer's disease.
• (Cannabidiol and Δ9-tetrahydrocannabinol)—Cannabidiol (nonpsychoactive) and Δ9-tetrahydrocannabinol (psychotropic) antioxidant.
• S-18986—Stimulates the growth of nerve cells in the hippocampus.

See also

• Cognitive science
• Eidetic memory
• Human enhancement
• Long-term potentiation
• Memory and aging
• Psychedelics in problem-solving experiment
• Psychoanaleptic

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    In a validated model of hippocampal-dependent memory impairment and synaptic plasticity changes by predator stress, acute tianeptine can prevent the deleterious effects of stress on spatial memory, an effect that does not depend on corticosterone levels (73). Tianeptine also facilitates focused attention behavior in the cat in response to its environment or towards a significant stimulus (74). It was shown to exert improving effects on learning as well as on working memory and on reference memory in rodents (72) and to exhibit vigilance-enhancing effects in rats (75) and monkeys (76)... {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
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External links

• "A Pandora's box full of smart drugs" by Ann Robinson (The Guardian: February 23, 2010)
• Greely, Henry; Sahakian, Barbara; Harris, John; Kessler, Ronald C.; Gazzaniga, Michael; Campbell, Philip; Farah, Martha J. (December 10, 2008). "Towards responsible use of cognitive-enhancing drugs by the healthy". Nature. 456 (7223). Nature Publishing Group: 702–5. Bibcode:2008Natur.456..702G. doi:10.1038/456702a. ISSN 1476-4687. OCLC 01586310. Retrieved March 25, 2014. {{cite journal}}: Unknown parameter |subscription= ignored (|url-access= suggested) (help)
• "Brain Gain: The underground world of "neuroenhancing" drugs" by Margaret Talbot (The New Yorker: April 27, 2009)
• Business Week Online – "I Can't Remember" September 1, 2003 at Business Week
• List of Nootropic drugs at Erowid
• Caffeine and L-Theanine Synergistic Properties

• Ill-formatted IPAc-en transclusions
• Misplaced Pages articles needing copy edit from April 2014
• Nootropics
• Amphetamine