Nootropic

Memory enhancers are often referred to as "smart drugs", "study drugs",^[1] "smart nutrients", "cognitive enhancers", "brain enhancers" or in the scientific literature as nootropics.^[2] They are drugs that are purported to improve human cognitive abilities.^[3][4] The term covers a broad range of substances including drugs, nutrients and herbs with purported cognitive enhancing effects.

The word nootropic was coined in 1964 by Dr. Corneliu E. Giurgea, derived from the Greek words noos, or "mind," and tropein meaning "to bend/turn". Typically, 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.

Currently there are several drugs on the market that improve memory, concentration, planning, and reduce impulsive behavior. Many more are in different stages of development.^[5] The most commonly used class of drug are the stimulants.^[6]

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.^[7] 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.

Nootropics are brain function or brain altering chemicals. Although many nootropics have been discovered with few effects (such as the racetams), any substance capable of altering the brain can produce harmful effects. An unapproved drug or dietary supplement does not have to have safety or efficacy approval before being sold.^[8] (this mainly applies to the U.S.A., but may not apply in the E.U. or elsewhere) This nootropic list is not meant to be sufficient to determine the safety of a substance or mixture. Second, any efficacy described on this page should be determined by references in the respective article, and if the claims are not referenced, at a minimum in a clinical study, the claim or claims should not be taken seriously.

Some dangers of nootropics include, but are not limited to:

• Downregulation of neurological activity upon stimulation, resulting in a permanent or temporary hypoactive system and/or addictive properties (applies to dopamine, choline, and many other neurotransmitter systems)
• Serotonin syndrome from serotonergic agents
• excessive acetylcholine receptor activation - see acetylcholinesterase inhibitor
• heart failure, such as that from stimulants or any substance which alters heart rate
• organ failure such as liver failure and kidney failure

This list is not exhaustive. Any non-essential substances should be only taken after consideration from a doctor or otherwise legally competent physician.

The 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.

The word nootropic was coined upon discovery of the effects of piracetam, developed in the 1960s.^[9] Although piracetam is the most commonly taken nootropic,^[10][9] there are many relatives in the racetam family which have different potencies and side effects. Based on the effects of piracetam, the main implicated pharmacology is alteration of blood flow and effects on the glutamate/gaba systems, causing changes downstream in the choline and monoaminergic systems.^{[citation needed]}

Stimulants are often seen as smart drugs. These typically improve concentration and cognitive performance, but only while the drug is still in the blood. Some scientists recommend widespread use (of Ritalin and Adderall) by the general population to increase brain power.^[6]

• Amphetamines (and related drugs)
  • Amphetamine - Dopaminergic
  • Cocaine - Dopaminergic
  • Methamphetamine - Dopaminergic, Serotonergic, Norepinephrigenic
  • Methylphenidate - Dopaminergic
  • Pemoline - Dopaminergic
• Eugeroics ("wakefulness enhancers") - unproven primary mechanisms but proven efficacy
  • Adrafinil
  • Armodafinil
  • Modafinil
• Xanthines
  • Caffeine - reduces fatigue perception
  • Theophylline

Dopaminergics 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 ritalin or amphetamine. Dopaminergic nootropics include dopamine synthesis precursors, dopamine reuptake inhibitors, monoamine oxidase inhibitors, and other compounds:

• Metabolic precursors - raise levels
  • L-Phenylalanine - purported cognitive improvement
  • L-Tyrosine - purported cognitive improvement
• Reuptake inhibitors - stabilize/improve levels
  • Amineptine - mild stimulant
• MAO-B inhibitors - prevent breakdown
  • Selegiline - mild stimulant
• Others
  • cocaine and the relatives - multiple mechanisms that amplify dopamine release
  • amphetamine and relatives
  • Yohimbe - purported dopaminergic activity

Memory can come from many different processes, but is dependent on the ability to store and recall information.

Cholinergics 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:

• Acetylcarnitine - Amino acid. functions in ActCh production (donating the acetyl portion to the acetylcholine molecule).
• Choline and its precursors - Precursor (chemistry) to acetylcholine
• Vitamin B5 - cofactor in the conversion of choline into acetylcholine
• Galantamine - acetylcholinesterase inhibitor
• Huperzine A - acetylcholinesterase inhibitor
• Donepezil - Drug. acetylcholinesterase inhibitor
• Rosemary - acetylcholinesterase inhibitor
• Sage - acetylcholinesterase inhibitor
• Coluracetam - choline uptake enhancer
• Meclofenoxate - Drug. Probable precursor approved for Dementia and Alzheimers
• Ispronicline - recently developed nicotinic acetylcholine receptor agonist
• Nicotine - Nicotinic acetylcholine receptor agonist
• Arecoline - Nicotinic acetylcholine receptor agonist

The GABA_A α5 receptor site has recently displayed memory improvements when agonized.

• α5IA - Highly selective experimental drug
• Suritozole - experimental - displays selectiveness

The 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

• CX-717 - Going through FDA approval for memory-impairing illnesses
• IDRA-21 - believed to improve memory by significantly enhancing long term potentiation but only used in animals - incredibly potent
• LY-503,430 - Being developed for Parkinsons but showing increase in BDNF, specifically in areas of memory and higher cognitive skills

Cyclic adenosine monophosphate is a secondary messenger which 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.

• Propentofylline - nonselective phosphodiesterase inhibitor with some neuroenhancement
• Rolipram - Drug. shows alertness enhancement, long term memory improvement and neuroprotection
• Mesembrine - PDE4-inhibitor with possible serotonergic activity

Serotonin 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:

• 5-HTP - precursor
• Tryptophan - Essential amino acid
• SSRIs - Class of antidepressants that increase active serotonin levels by inhibiting its reuptake. Have also been shown to promote Neurogenesis in the hippocampus.
• Tianeptine - paradoxical antidepressant, improves mood and reduces anxiety
• Methamphetamine - some serotonin activity

Stress, 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.

Below are a list of substances that may have not been already mention earlier on the page:

• Beta blockers - anxiolytic
• Kava kava - mild stimulant used in relaxation
• Lemon Balm - Displays adaptogen properties
• Passion Flower - possible MAOI and neurotransmitter reuptake activity
• Rhodiola Rosea - possible MAOI activity
• St John's Wort - herbal SSRI that has been approved (in Europe) to treat mild depression
• ginseng (including Siberian ginseng) - adaptogenic effects shown
• Sutherlandia frutescens - possible anti-inflammatory reducing pain from those illnesses
• Tea - contains many different adaptogens
• Theanine - GABAergic activity producing relaxation
• Grape seed extract - has shown some efficacy in reducing bodily stress
• Adafenoxate - possible anti-anxiety effect
• Butea frondosa - possible anti-anxiety effect^[11]
• Gotu Kola - adaptogen and anxiolytic

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. Vasodilators mentioned are only this which have shown, at minimum, probable mental enhancement.

• Coenzyme q-10 - 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
• Vinpocetine - increases blood circulation (vasodilator) and metabolism in the brain
• Picamilon - GABA activity and blood flow improver
• Ginkgo biloba - vasodilator

Nerves 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.

• Idebenone - antioxidant
• Inositol - implicated in memory function, deficit linked to some psychiatric illnesses
• dopamine enhancers - dopamine is an antioxidant and can enhance dendrite extension
• Anticonvulsants inhibit seizure related brain malfunction if a person has seizures
• Phosphatidylserine - possible membrane stabilizer

Many recreational substances which 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. These drugs are assumed to have significant dependency or abuse potential, either physically, psychologically, or both. 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.

• Tetrahydrocannabinol - Anxiolytic and analgesic found in cannabis. Neuroprotectant, possible alzheimers prevention and possible neurogenesis inducer
• Amphetamine-type stimulants are described above
• LSD - Psychedelic drug. At sub-recreational doses serotonin activity could alter neurogenesis and improve mood.
• 4-methylaminorex - similar to Modafinil but significantly more abuse potential
• Most Entheogens, including hallucinogens - drugs or substances which have shown value in psychotherapy, like mescaline, MDMA, and others
• MDPV - designer drug, 4x as potent as methylphenidate, greater abuse potential
• Tobacco - Contains nicotine and also has significant MAOI activity

Diet can have the greatest effect on cognition and the brain, as there are many necessary things which must be consumed. However, other substances have been linked to certain benefits, and may be predominant in certain foods.

Some regular food items contain substances with alleged nootropic benefits:

• Hemp - seeds as source of omega-3 fatty acids (see essential fatty acid), leafes ..
• fish - sources of omega-3 fatty acids (see essential fatty acid)
• Berries - may contain high levels of antioxidants

These are hormones that have activity not necessarily attributable to another specific chemical interaction, but have shown effectiveness. Only specific nootropic effects are stated.

• Vasopressin - memory hormone that improves both memory encoding and recall
• Pregnenolone - increases neurogenesis
• Orexin - Significant wakefulness promoter

These 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.

• DHEA - Precursor to Estrogen and Testosterone

Other agents purported to have nootropic claims but do not have (as of yet) attributable mechanisms or have clinically insignificant effects (but may upon refinement of administration) to warrant inclusion into other sections are mentioned here.

Nootropics with proven or purported benefits:

• Bacopa monniera - elevates curiosity, enhances memory and concentration.^[12]
• Brahmi rasayana - improved learning and memory in mice.^[13]
• Ergoloid mesylates - Drug. Similar to LSD. Used against Dementia and Alzheimers
• Fipexide - drug for Dementia
• Gerovital H3 - famous anti-aging mixture, most effects disproven, but some mind enhancement shown
• Sulbutiamine - Drug. Some shown memory improvement
• Royal Jelly - Increases brain cell growth and diversity, only proven in-vitro, improbable in-vivo
• Curcumin - Significant in-vitro activity, but in-vivo activity is limited by low bioavailability

These are substances or substance control which typically may have been linked to better cognitive function, but may not be the cause. See correlation does not imply causation

• Moderate use of alcohol - Moderate drinking has been associated with better cognitive ability than both abstention and heavy drinking.^{[14][15][16][17][18]}

Action potential Aging and memory Brain Central nervous system (CNS) Dendrite Human brain Long-term potentiation Nervous system

Neurite Neuron Neuroplasticity Neuroscience Neurotransmitter Sensory neuroscience Synapse Synaptic plasticity List of nootropics (smart drugs)

Abstract thinking Attention Attitude Brainstorming Cognition Cognitive science Creative thinking Critical thinking Curiosity Decision Decision making Eidetic memory Emotions and feelings Emotional intelligence Goals and goal setting Idea Imagination Intelligence Introspection

Lateral thinking Learning Memory Memory-prediction framework Mental calculation Mind's eye Mindset Mood Motivation Perception Personality Picture thinking Problem shaping Problem solving Reason Recollection (recall) Self-reflection Thought Visual thinking

Anxiety Cognitive psychology Clinical depression Confusion Cosmetic pharmacology Drug Parasympathomimetics Prescription drug Prohibition (drugs) Psychoactive drug (aka psychotropic drug) Psychedelic drug

Human enhancement Ergogenic aid Life extension Neurodegenerative disease Alzheimer's disease Parkinson's disease Nutrition Sleep disorders Stress Stress management

• Greely H, Sahakian B, Harris J; et al. (2008). "Towards responsible use of cognitive-enhancing drugs by the healthy". Nature. 456 (7223): 702–5. doi:10.1038/456702a. PMID 19060880. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
• Business Week Online - "I Can't Remember" September 1, 2003 at Business Week
• List of Nootropic drugs at Erowid