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Nootropics, also referred to as smart drugs, memory enhancers, and cognitive enhancers, are drugs, supplements, nutraceuticals, and functional foods that are purported to improve mental functions such as cognition, memory, intelligence, motivation, attention, and concentration.[1][2] The word nootropic was coined in 1964 by the Romanian Dr. Corneliu E. Giurgea, derived from the Greek words noos, or "mind," and tropein 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. However the efficacy of nootropic substances in most cases has not been conclusively determined. This is complicated by the difficulty of defining and quantifying cognition and intelligence. [edit] Availability and prevalenceAt present, there are several drugs on the market that improve memory, concentration, planning, and reduce impulsive behavior. Many more are in different stages of development.[3] The most commonly used class of drug are the stimulants.[4] These drugs are used primarily to treat people with cognitive difficulties: Alzheimer's disease, Parkinson's disease, ADHD. However, more widespread use is being recommended by some researchers[5]. These drugs have a variety of human enhancement applications as well, and are marketed heavily on the World-Wide Web. Nevertheless, intense marketing may not correlate with efficacy; while scientific studies support some of the claimed benefits, it is worth noting that many of the claims attributed to most nootropics have not been formally tested. In academia, modafinil has been used to increase productivity, although its long-term effects have not been assessed in healthy individuals.[3] Stimulants such as methylphenidate and atomoxetine are being used on college campuses, and by an increasingly younger group.[3] One survey found that 7% of students had used stimulants for a cognitive edge in the past year, and on some campuses the number is as high as 25%.[4] [edit] HazardsThe 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.[3] Dr. Corneliu E. Giurgea originally coined the word nootropics for brain-enhancing drugs with very few side-effects. Racetams are sometimes cited as an example of a nootropic with few effects and wide therapeutic window;[6] however, any substance ingested could produce harmful effects. An unapproved drug or dietary supplement does not have to have safety or efficacy approval before being sold.[7] (This mainly applies to the USA, but may not apply in the EU or elsewhere.) Some dangers of nootropics include, but are not limited to:
[edit] ExamplesThe term "drug" here is used as a legal designation. Although some of the effects of these substances may be similar to others, only those substances that have shown cognitive effects are included. [edit] Nootropics and racetamsThe word nootropic was coined upon discovery of the effects of piracetam, developed in the 1960s.[8] Although piracetam is the most commonly taken nootropic,[8] there are many relatives in the family that have different potencies and side-effects. Other common racetams include pramiracetam, oxiracetam, and aniracetam. There is no generally-accepted mechanism for racetams. In general, they show no affinity for the most important receptors, although modulation of most important central neurotransmitters, including acetylcholine and glutamate, have been reported.[9] Although aniracetam and nebracetam show affinity for muscarinic receptors, only nefiracetam shows it at the nanomolar range. Racetams have been called "pharmacologically safe" drugs.[6] Other substances sometimes classified as nootropics include hydergine, vinpocetine, bifemelane, huperzine A (cholinergic activator below), and dimethylaminoethanol.[6] [edit] StimulantsStimulants are often seen as smart drugs, but are actually just productivity enhancers. These typically improve concentration and a few areas of cognitive performance, but only while the drug is still in the blood. Some scientists recommend widespread use of stimulants such as methylphenidate and amphetamines by the general population to increase brain power.[4][10]
[edit] DopaminergicsDopaminergics are substances that affect the neurotransmitter dopamine or the components of the nervous system that use dopamine. Attributable effects of dopamine are enhancement of attention, alertness, and antioxidant activity. Dopamine is the primary activity of stimulants like methylphenidate (Ritalin) or amphetamine. Dopaminergic nootropics include dopamine synthesis precursors, dopamine reuptake inhibitors, monoamine oxidase inhibitors, and other compounds:
[edit] Memory enhancementMemory can come from many different processes, but is dependent on the ability to store and recall information. [edit] CholinergicsCholinergics are substances that affect the neurotransmitter acetylcholine or the components of the nervous system that use acetylcholine. Acetylcholine is a facilitator of memory formation. Increasing the availability of this neurotransmitter in the brain may improve these functions. Cholinergic nootropics include acetylcholine precursors and cofactors, and acetylcholinesterase inhibitors:
[edit] GABA blockersThe GABAA α5 receptor site has recently displayed memory improvements when inverse agonized.
[edit] Glutamate activatorsThe AMPA transmitter and the AMPA receptors are currently being researched with significant memory improvements and possible alertness enhancement when agonized. The drug class for AMPA system modulation is called Ampakines. Although there are many in-research ones, the main ones mentioned will be the ones possibly coming to market or are significantly notable. Some racetams have shown this activity
[edit] cAMPCyclic adenosine monophosphate is a secondary messenger that, if increased, has shown memory improvements. One common method is by decreasing the activity of phosphodiesterase-4, an enzyme that breaks down cAMP. Typical effects include wakefulness and memory enhancement.
[edit] SerotonergicsSerotonin is a neurotransmitter with various effects on mood and possible effects on neurogenesis. Serotonergics are substances that affect the neurotransmitter serotonin or the components of the nervous system that use serotonin. Serotonergic nootropics include serotonin precursors and cofactors, and serotonin reuptake inhibitors:
[edit] Anti-depression, adaptogenic (antistress), and mood stabilizationStress, depression, and depressed mood negatively affect cognitive performance. It is reasoned that counteracting and preventing depression and stress may be an effective nootropic strategy. The term adaptogen applies to most herbal anti-stress claims. The substances below may not have been mentioned earlier on the page:
[edit] Blood flow and metabolic functionBrain 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. Vasodilators mentioned are only those which have shown, at minimum, probable mental enhancement.
[edit] Nerve growth stimulation and brain cell protectionNerves are necessary to the foundation of brain communication and their degeneracy, underperformance, or lacking can have disastrous results on brain functions. Antioxidants are frequently used to prevent oxidative stress, but do not improve brain function if that is their only activity.
[edit] Recreational drugsMany recreational substances that are currently illegal or heavily controlled have effects on the brain or long-term functions that are typically considered secondary to their effects on perception. Note that this list is not intended to be exhaustive. This list include substances which are illegal, or not completely illegal, but are controlled or exempt under a Drug schedule. See also: Controlled substances act and Misuse of Drugs Act 1971
[edit] Dietary nootropicsDiet can have the greatest effect on cognition and the brain, as there are many necessary things that must be consumed. However, other substances have been linked to certain benefits, and may be predominant in certain foods. Studies have been able to link vitamin B1, vitamin B12, omega-3, caffeine, antioxidants, protein and iron to brain function. It is crucial to obtain the nutrients that increase cognitive function directly, as well as those that effect how those nutrients are absorbed and used in the body. Vitamin B1, thiamin, aids nerve cell function and helps the body convert food, specifically carbohydrates, into fuel, known as glucose. Glucose is what the brain runs off of, making it crucial for the brain. Foods containing Vitamin B1, include whole grains, rice, wheat germ, bran and organ meats. B12, cobalamin, is used to make neurotransmitters. They also maintain the nervous system by helping to metabolize fatty acids, which are essential for the maintenance of myelin, which surrounds nerves. Vitamin B12 is found primarily in animal products, but it may also be found in soy products, eggs, seaweeds and algae. Low amounts of vitamin B12 with normal folate have been shown to cognitive impairment and anemia, while High amounts of folate and normal vitamin B 12 have been shown to improve cognitive function.[12] Traditional sources of omega 3, an unsaturated fat, could be found richly in cattle, since they used to graze on grass, which contains omega 3, but today they are mostly fed grain, which does not contain omega 3’s. Today’s society gets a bit too much omega 6, and less of omega-3. Omega-3, alpha linolenic acid, has a strong influence on the brain. They influence both communication between cells and cell function. It appears to make receptors on the cell membranes who are more sensitive to serotonin, a neurotransmitter, which helps give us a “happy” feeling. Omega-3 has also been linked to helping retain brain function. A study done in Norway proved how omega 3 eaten during pregnancy helped to produce a more intelligent child. Higher omega-3 has been shown to lower risk of depression, even better than depression medication. Omega - 3’s are what build cell membranes. Omega 3’s can be found in cold water fish, such as salmon, as well as almonds, avocadoes, walnuts and flaxseed. Fish oils in particular, are components of nerve cell membranes and myelin, which help to keep blood vessels in the brain healthy (Chillot, 2004). On a side note, in terms of fats in general, high saturated fat diets have been linked to worsen memory. Caffeine effects on the brain are quite controversial. Some admit to their effect on the brain, while others deny any benefits, due to its addictive affects. Caffeine has been shown to help improve short-term concentration and facilitate learning, as well as memory. Caffeine dilates the blood vessels in the brain, if consumed in small amounts. In low doses it increases alertness, but a high dose is needed to show improved performance. After consumption, it is rapidly distributed throughout the body and blocks actions of endogenous adenosine at adenosine A1 and A2 receptors resulting in different physiological effects. The blockage is how caffeine can affect alertness and performance, since adenosine is closely involved in sleep regulation. Antioxidants have been found to be very beneficial to brain functioning in many ways. The more commonly known aspect of antioxidant on the brain, would be their protection for oxidative damage. A recent study which lasted three – six years, showed how vegetables, most likely due to their vitamin E, folate and antioxidant content, helped people to retain their mental abilities longer, keeping their brain younger (Environmental Nutrition, 2009). Those vegetables emphasized were leafy green or cruciferous vegetables (Environmental Nutrition, 2009). It was also found that consumption of isoflavonoes of 50 mg of soy dietary supplements twice a day for three weeks, decreased a biomarker of DNA oxidation damage. Isoflavones are a plant derived class of phytoestrogens. Isoflavones are richest in soy products, but can also be found in foods such as legumes. It is not overwhelming, but there is some evidence suggesting that isoflavones may protect the brain from cognitive decline. M.C.Y. Wong et al. found that the UK the Joint Health believed that soy protein helps to reduce cholesterol, which may impact how the brain works. Another study that looked mainly at the effects of soy on females during their cycle, since their estrogen levels constantly changed, suggested that dietary phytoestrogesn may have effects on cognitive function in females and that soy appeared to affect some cognitive processes. (Nutritional Nerosicence, 2008). Polyphenolics in fruits and vegetables help brain functioning. The darker colored fruits and vegetables tend to be high in phenolics, therefore possessing large antioxidant and inflammatory activity. At such levels, it has been shown that these effects can retard and reverse bits of brain aging, such as dopamine release and other cognitive deficits. The polyphenols increased antioxidant and anti-inflammatory levels. Such effects are particularly effective with dietary intake of berry fruit. A study was done on rats, where a 2% blackberry supplemented diet was proven effective in reversing age related deficits and neural function. This diet helped improve motor performance base don three tasks. Polyphenolics positively effect brain signaling to enhance neural communication. Berries are also high in flavonoices, condensed and hydrolysable tannins, phenolic acids and stillbenoids, amongst other properties, such as Cyanidin-3-O-glucoside, which has the highest oxygen radial absorbance capacity among anthocyanins. Blackberries are so high in antiproliferative, antioxidant and anti-inflammatory activities, making them a great food for the brain. In one study proving the benefits of blackberries, rats were fed a 2% blackberry diet, and they were able to perform much better on behavioral tests than the control rats. According to Nutritional Neuroscience, blackberry juice and its main anthocyanin component, cyaniding-3-O-glucoside had been seen to the protective effect against free radical-medicated endothelial dysfunction and vascular failure Blackberries, like blueberries, may exert their protective effects directly through alterations in cell signaling to improve or increase neuronal communication, calcium buffering ability, neuroprotective stress shock proteins, plasticity an stress signaling pathways (Barbara, 2009). The study had found that the blueberry diet improved spatial working memory in older rats, and changes were regulated by the CREB and BDNF pathway in the hippocampus. Anthocyanins, which are found in blueberries and blackberries, enter the brain and improve cognitive function. Adult brains used amino acids, which are typically found in protein rich food, for the production of enzymes that transport molecules, structural material and neurotransmitters, along with other essential molecules. Some of the amino acids include tyrosine and phenylalanine, which help to produce the hormone epinephrine and neurotransmitter dopamine. These two hormones help create alertness. Therefore it is suggested to eat low calorie, but high protein meals, so people are more alert and attentive. Although to much protein can have a negative effect as well. In addition to toxicity which too high protein levels can cause, food high in protein have les tyrpotophan, a neurot transmitter of serotonin. Tyrptophan helps to stablize mood and may also influence the cognitive process, specifically learning and memory. There have been both human and rat studies which have indicated a deficit in long term memory and information processing due to tryptophan depletion and other studies show how tryptophan helps to improve decision making. Although, carbohydrates, which don’t contain tryptophan, help to push it into the brain, by triggering the release of insulin. Insulin stimulates muscles to take up competing amino acids. Even, calcium, which typically comes in many foods with protein, helps regulate nerve impulse transmittion (Kiefer, 2007). Two other important neurotransmitters are acetycholine and serotonin. Acetycholine is essential in memory formation and maintenance. It is found in egg yolks and organ meats. Creation and utilization of acetylcholine is crutial to memory. Serotonin helps with sleep regulation and anxiety reduction. It is manufactured from tryptophan (Blaun, 1996). Iron is also important for staying mentally sharp. Iron helps create hemoglobin, an iron containing protein in red blood cells, which transport oxygen to the brain. Oxygen in the brain is vital, since it helps to metabolize glucose. If a child does not receive enough iron, it can impair brain development and lead to deficits in speech, math and reading. Women of reproductive age need the most iron, and therefore may be more likely to end up with a deficiency. Those with sufficient iron int heir blood have been proven to perform better cognitive tests than those who were iron-deficient. [edit] Direct hormonesThese are hormones that have activity not necessarily attributable to another specific chemical interaction, but have shown effectiveness. Only specific nootropic effects are stated.
[edit] Secondary enhancersThese are substances which by themselves may not improve brain function, but may have benefits for those lacking them (in the case of hormones) or may alter the balance of neurotransmitters.
[edit] Unknown enhancementOther agents purported to have nootropic effects but which do not (yet) have attributable mechanisms or clinically significant effects (but may upon refinement of administration) are mentioned here. Nootropics with proven or purported benefits:
[edit] Other nootropicsThese substances have been linked to better cognitive function, but may not be the cause. See correlation does not imply causation
[edit] See also
[edit] Brain and neurology[edit] Thought and thinking (what nootropics are used for)[edit] Health[edit] References
[edit] External links
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