Nootropics ( , or ) (

colloquial Colloquialism (), also called colloquial language, everyday language or general parlance, is the linguistic style used for casual (informal) communication. It is the most common functional style of speech, the idiom normally employed in convers ...

: smart drugs and cognitive enhancers, similar to

adaptogen Adaptogens or adaptogenic substances are used in herbal medicine for the claimed stabilization of physiological processes and promotion of homeostasis. History The concept of adaptogens was originally created in 1947 to describe a substance tha ...

s) are a wide range of natural or synthetic

supplements Supplement or Supplemental may refer to: Health and medicine * Bodybuilding supplement * Dietary supplement * Herbal supplement Media * Supplement (publishing), a publication that has a role secondary to that of another preceding or concurre ...

drug A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via inhal ...

s and other substances that are claimed to improve

cognitive function Cognitive skills, also called cognitive functions, cognitive abilities or cognitive capacities, are brain-based skills which are needed in acquisition of knowledge, manipulation of information and reasoning. They have more to do with the mechanisms ...

or to promote relaxation, particularly boosting mood,

executive functions In cognitive science and neuropsychology, executive functions (collectively referred to as executive function and cognitive control) are a set of cognitive processes that are necessary for the cognitive control of behavior: selecting and succ ...

attention Attention is the behavioral and cognitive process of selectively concentrating on a discrete aspect of information, whether considered subjective or objective, while ignoring other perceivable information. William James (1890) wrote that "Att ...

, memory, creativity, or

motivation Motivation is the reason for which humans and other animals initiate, continue, or terminate a behavior at a given time. Motivational states are commonly understood as forces acting within the agent that create a disposition to engage in goal-dire ...

in healthy individuals. The use of cognition-enhancing supplements by healthy individuals in the absence of a

medical indication In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. There can be multiple indications to use a procedure or medication. An indication can commonly be confused with the term diagnosis. A diagnosis ...

spans numerous controversial issues, including the

ethics Ethics or moral philosophy is a branch of philosophy that "involves systematizing, defending, and recommending concepts of right and wrong behavior".''Internet Encyclopedia of Philosophy'' The field of ethics, along with aesthetics, concerns ...

and fairness of their use, concerns over

adverse effect An adverse effect is an undesired harmful effect resulting from a Pharmaceutical drug, medication or other Surgery#Definitions, intervention, such as surgery. An adverse effect may be termed a "side effect", when judged to be secondary to a main ...

s, and the diversion of

prescription drug A prescription drug (also prescription medication or prescription medicine) is a pharmaceutical drug that legally requires a medical prescription to be dispensed. In contrast, over-the-counter drugs can be obtained without a prescription. The rea ...

s for non-medical uses. Nonetheless, the international sales of cognitive- or mood-enhancing supplements have continued to grow over time and in 2012 reached 0.69 billion. With sales supported by global health trends, the market is expected to reach

US$ The United States dollar (symbol: $; code: USD; also abbreviated US$ or U.S. Dollar, to distinguish it from other dollar-denominated currencies; referred to as the dollar, U.S. dollar, American dollar, or colloquially buck) is the official ...

33.85 billion by the year 2030, at a

CAGR Compound annual growth rate (CAGR) is a business and investing specific term for the geometric progression ratio that provides a constant rate of return over the time period. CAGR is not an accounting term, but it is often used to describe some ele ...

of 14.8%. While most nootropics are not regulated, there are other nootropics like

theanine Theanine , also known as L-γ-glutamylethylamide and ''N''5-ethyl-L-glutamine, is an amino acid analogue of the proteinogenic amino acids L-glutamate and L-glutamine and is found primarily in particular plant and fungal species. It was disco ...

, which the

Food and Drug Administration (FDA) Food is any substance consumed by an organism for Nutrient, nutritional support. Food is usually of plant, animal, or Fungus, fungal origin, and contains essential nutrients, such as carbohydrates, fats, protein (nutrient), proteins, vitamins ...

considers to be generally recognized as safe (GRAS) and allows its sale as a dietary supplement. They are often found in supplement form as

nutraceutical A nutraceutical or bioceutical is a pharmaceutical alternative which claims physiological benefits. In the US, "nutraceuticals" are largely unregulated, as they exist in the same category as dietary supplements and food additives by the FDA, unde ...

s, or in recent years, as

functional Functional may refer to: * Movements in architecture: ** Functionalism (architecture) ** Form follows function * Functional group, combination of atoms within molecules * Medical conditions without currently visible organic basis: ** Functional s ...

food or drinks. Recently, some companies even began using nootropics in

beer Beer is one of the oldest and the most widely consumed type of alcoholic drink in the world, and the third most popular drink overall after water and tea. It is produced by the brewing and fermentation of starches, mainly derived from cer ...

as an

alcohol Alcohol most commonly refers to: * Alcohol (chemistry), an organic compound in which a hydroxyl group is bound to a carbon atom * Alcohol (drug), an intoxicant found in alcoholic drinks Alcohol may also refer to: Chemicals * Ethanol, one of sev ...

replacement.

History and definition

The term ''nootropic'' is derived . It was first introduced by Corneliu Giurgea in 1972 to describe a new classification of molecules that acted selectively towards the brain's higher-level integrative activity. In order for a product to qualify as a true nootropic, it must fulfill Giurgea's five criteria for the category. # It should aid with improvement in working memory and learning. # Supports brain function under hypoxic conditions or after electroconvulsive therapy. # Protection of the brain from physical or chemical toxicity. # Natural cognitive functions are enhanced. # It requires to be non-toxic to humans, without depression or stimulation of the brain.

Marketing claims

Nootropics are often advertised with unproven claims of effectiveness at improving cognition. The FDA and FTC warned manufacturers and consumers in 2019 about possible advertising fraud and marketing scams concerning nootropic supplement products. The FDA and FTC stated that some nootropic products had not been approved as a

effective for any medical purpose, were not proven to be safe, and were illegally marketed in the United States under violation of the

Federal Food, Drug, and Cosmetic Act The United States Federal Food, Drug, and Cosmetic Act (abbreviated as FFDCA, FDCA, or FD&C) is a set of laws passed by the United States Congress in 1938 giving authority to the U.S. Food and Drug Administration (FDA) to oversee the safety of f ...

. Having said that, there are some nootropics like

Theanine Theanine , also known as L-γ-glutamylethylamide and ''N''5-ethyl-L-glutamine, is an amino acid analogue of the proteinogenic amino acids L-glutamate and L-glutamine and is found primarily in particular plant and fungal species. It was disco ...

, that the

considered generally recognized as safe (GRAS) and allows its sale as a dietary supplement. In 2018 in the United States, some nootropic supplements were identified as having misleading ingredients and illegal marketing. In 2019, the US

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

(FDA) and Federal Trade Commission (FTC) warned manufacturers and consumers about possible

advertising fraud Ad fraud (also referred to as ''Click Fraud or PPC Fraud)'' is concerned with the practice of fraudulently representing online advertisement impressions, clicks, conversion or data events in order to generate revenue. Ad-frauds are particularly po ...

and marketing scams concerning nootropic supplements. Over the years 2010 to 2019, the FDA warned numerous supplement manufacturers about the illegal status of their products as unapproved drugs with no proven safety or efficacy at the doses recommended, together with misleading marketing.

Availability and prevalence

In 2008, the most commonly used class of drug was

stimulants Stimulants (also often referred to as psychostimulants or colloquially as uppers) is an overarching term that covers many drugs including those that increase activity of the central nervous system and the body, drugs that are pleasurable and inv ...

, such as

caffeine Caffeine is a central nervous system (CNS) stimulant of the methylxanthine class. It is mainly used recreationally as a cognitive enhancer, increasing alertness and attentional performance. Caffeine acts by blocking binding of adenosine t ...

. Manufacturers' marketing claims for

dietary supplements A dietary supplement is a manufactured product intended to supplement one's diet by taking a pill, capsule, tablet, powder, or liquid. A supplement can provide nutrients either extracted from food sources or that are synthetic in order ...

are usually not formally tested and verified by independent entities. In 2016, the

American Medical Association The American Medical Association (AMA) is a professional association and lobbying group of physicians and medical students. Founded in 1847, it is headquartered in Chicago, Illinois. Membership was approximately 240,000 in 2016. The AMA's stat ...

adopted a policy to discourage prescriptions of nootropics for healthy people, on the basis that the cognitive effects appear to be highly variable among individuals, are dose-dependent, and limited or modest at best.

Use by students

The use of prescription stimulants is especially prevalent among students. Surveys suggest that 0.7–4.5% of German students have used cognitive enhancers in their lifetimes. Stimulants such as dimethylamylamine and

methylphenidate Methylphenidate, sold under the brand names Ritalin and Concerta among others, is the most widely prescribed central nervous system (CNS) stimulant medication used to treat attention deficit hyperactivity disorder (ADHD) and, to a lesser extent ...

are used on college campuses and by younger groups. Based upon studies of self-reported illicit stimulant use, of college students use diverted ADHD stimulants, which are primarily used for enhancement of academic performance rather than as recreational drugs. Several factors positively and negatively influence an individual's willingness to use a drug for the purpose of enhancing cognitive performance. Among them are personal characteristics, drug characteristics, and characteristics of the social context.

Side effects

The main concern with

pharmaceutical drug A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy ( pharmacotherapy) is an important part of the medical field and ...

s is

s, which also apply to nootropics with undefined effect. Long-term safety evidence is typically unavailable for nootropics.

Racetam Racetams are a class of drugs that share a pyrrolidone nucleus. Some, such as piracetam, aniracetam, oxiracetam, pramiracetam and phenylpiracetam are considered nootropics. Others such as levetiracetam, brivaracetam, and seletracetam are a ...

piracetam Piracetam is a drug marketed as a treatment for myoclonus. It is also used as a cognitive enhancer to improve memory, attention, and learning. Evidence to support its use is unclear, with some studies showing modest benefits in specific populati ...

and other compounds that are structurally related to piracetam, have few serious adverse effects and low

toxicity Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a subs ...

, but there is little evidence that they enhance cognition in people having no cognitive impairments. In the United States,

dietary supplement A dietary supplement is a manufactured product intended to supplement one's diet by taking a pill, capsule, tablet, powder, or liquid. A supplement can provide nutrients either extracted from food sources or that are synthetic in orde ...

s may be marketed if the manufacturer can show that the supplement is generally recognized as safe, and if the manufacturer does not make any claims about using the supplement to treat or prevent any disease or condition; supplements that contain

drugs A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via inhalat ...

or advertise

health claim A health claim on a food label and in food marketing is a claim by a manufacturer of food products that their food will reduce the risk of developing a disease or condition. For example, it is claimed by the manufacturers of oat cereals that oa ...

s are illegal under US law.

Types

Central nervous system stimulants

Systematic review A systematic review is a scholarly synthesis of the evidence on a clearly presented topic using critical methods to identify, define and assess research on the topic. A systematic review extracts and interprets data from published studies on t ...

s and

meta-analyses A meta-analysis is a statistical analysis that combines the results of multiple scientific studies. Meta-analyses can be performed when there are multiple scientific studies addressing the same question, with each individual study reporting me ...

of clinical human research using low doses of certain

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...

stimulant Stimulants (also often referred to as psychostimulants or colloquially as uppers) is an overarching term that covers many drugs including those that increase activity of the central nervous system and the body, drugs that are pleasurable and inv ...

s found that these drugs enhance cognition in healthy people. In particular, the classes of stimulants that demonstrate cognition-enhancing effects in humans act as direct agonists or

indirect agonist In pharmacology, an indirect agonist or indirect-acting agonist is a substance that enhances the release or action of an endogenous neurotransmitter but has no specific agonist activity at the neurotransmitter receptor itself. Indirect agonists wor ...

s of dopamine receptor D₁, adrenoceptor A₂, or both types of receptor in the

prefrontal cortex In mammalian brain anatomy, the prefrontal cortex (PFC) covers the front part of the frontal lobe of the cerebral cortex. The PFC contains the Brodmann areas BA8, BA9, BA10, BA11, BA12, BA13, BA14, BA24, BA25, BA32, BA44, BA45, BA ...

. Relatively high doses of stimulants cause cognitive deficits. *

Amphetamine Amphetamine (contracted from alpha- methylphenethylamine) is a strong central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity. It is also commonly used ...

systematic reviews and meta-analyses report that low-dose amphetamine improves cognitive functions (e.g.,

inhibitory control Inhibitory control, also known as response inhibition, is a cognitive process – and, more specifically, an executive function – that permits an individual to inhibit their impulses and natural, habitual, or dominant behavioral r ...

episodic memory Episodic memory is the memory of everyday events (such as times, location geography, associated emotions, and other contextual information) that can be explicitly stated or conjured. It is the collection of past personal experiences that occurred ...

working memory Working memory is a cognitive system with a limited capacity that can hold information temporarily. It is important for reasoning and the guidance of decision-making and behavior. Working memory is often used synonymously with short-term memory, ...

, and aspects of

) in healthy people and in individuals with ADHD. A 2014 systematic review noted that low doses of amphetamine also improve

memory consolidation Memory consolidation is a category of processes that stabilize a memory trace after its initial acquisition. A memory trace is a change in the nervous system caused by memorizing something. Consolidation is distinguished into two specific processe ...

, 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 required a high degree of effort. *

Methylphenidate Methylphenidate, sold under the brand names Ritalin and Concerta among others, is the most widely prescribed central nervous system (CNS) stimulant medication used to treat attention deficit hyperactivity disorder (ADHD) and, to a lesser extent ...

a benzylpiperidine derivative that improves

, and

, aspects of

, and planning latency in healthy people. It also may improve task saliency and performance on tedious tasks. At above optimal doses, methylphenidate has off–target effects that decrease learning. *

Eugeroics Eugeroics (originally "eugrégorique" or "eugregoric"), also known as wakefulness-promoting agents and wakefulness-promoting drugs, are a class of drugs that promote wakefulness and alertness. They are medically indicated for the Pharmacotherapy, ...

(

armodafinil Armodafinil (trade name Nuvigil) is the enantiopure compound of the eugeroic modafinil (Provigil). It consists of only the (''R'')-(−)-enantiomer of the racemic modafinil. Armodafinil is produced by the pharmaceutical company Cephalon Inc ...

and

modafinil Modafinil, sold under the brand name Provigil among others, is a central nervous system (CNS) stimulant medication used to treat sleepiness due to narcolepsy, shift work sleep disorder, and obstructive sleep apnea. While it has seen off-label ...

) are classified as "wakefulness-promoting agents"; modafinil increases alertness, particularly in sleep-deprived individuals, and facilitates reasoning and problem solving in non-ADHD youth. In a systematic review of small, preliminary studies where the effects of modafinil were examined, when simple psychometric assessments were considered, modafinil intake enhanced executive function. Modafinil may not produce improvements in mood or motivation in sleep deprived or non-sleep deprived individuals. *

Caffeine Caffeine is a central nervous system (CNS) stimulant of the methylxanthine class. It is mainly used recreationally as a cognitive enhancer, increasing alertness and attentional performance. Caffeine acts by blocking binding of adenosine t ...

a meta-analysis found an increase in alertness and attentional performance. * Nicotine a meta-analysis of 41 clinical studies concluded that nicotine administration or smoking improves alerting and orienting attention and episodic and working memory and slightly improves fine motor performance.

Amino acids

A 2016 review reported that

may increase

alpha wave Alpha waves, or the alpha rhythm, are neural oscillations in the frequency range of 8–12 Hz likely originating from the synchronous and coherent ( in phase or constructive) electrical activity of thalamic pacemaker cells in humans. Historic ...

s in the brain. Alpha waves may contribute to a relaxed yet alert mental state. Another study has shown that an oral administration of

at doses of 50–200 mg promoted "relaxation without causing drowsiness" within 40 mins after consumption. A 2014 systematic review and meta-analysis found that concurrent caffeine and -theanine use had

synergistic Synergy is an interaction or cooperation giving rise to a whole that is greater than the simple sum of its parts. The term ''synergy'' comes from the Attic Greek word συνεργία ' from ', , meaning "working together". History In Christi ...

psychoactive effects that promoted alertness, attention, and task switching. These effects were most pronounced during the first hour post-dose. *

a study found that in healthy human subjects, ''α''-waves were generated on the occipital and parietal regions of the brain surface within 40 min after the oral administration of

(50–200 mg), signifying relaxation without causing drowsiness.

Racetams

Racetams, such as

, oxiracetam, phenylpiracetam, and

aniracetam Aniracetam (brand names Draganon, Sarpul, Ampamet, Memodrin, Referan), also known as ''N''-anisoyl-2-pyrrolidinone, is a racetam which is sold in Europe as a prescription drug. It is not approved by the Food and Drug Administration for use in th ...

, are often marketed as cognitive enhancers and sold

over the counter Over-the-counter (OTC) drugs are medicines sold directly to a consumer without a requirement for a prescription from a healthcare professional, as opposed to prescription drugs, which may be supplied only to consumers possessing a valid prescr ...

. A 2019 study found that piracetam supplements sold in the United States were inaccurately labeled. Racetams are often referred to as nootropics, but this property is not well established. The racetams have poorly understood mechanisms, although piracetam and aniracetam are known to act as

positive allosteric modulator In pharmacology and biochemistry, allosteric modulators are a group of substances that bind to a receptor to change that receptor's response to stimulus. Some of them, like benzodiazepines, are drugs. The site that an allosteric modulator binds to ...

s of

AMPA receptor The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (also known as AMPA receptor, AMPAR, or quisqualate receptor) is an ionotropic transmembrane receptor for glutamate (iGluR) that mediates fast synaptic transmission in the ce ...

s and appear to modulate

cholinergic Cholinergic agents are compounds which mimic the action of acetylcholine and/or butyrylcholine. In general, the word "choline" describes the various quaternary ammonium salts containing the ''N'',''N'',''N''-trimethylethanolammonium cation. ...

systems. According to the US

Piracetam is not a
vitamin A vitamin is an organic molecule (or a set of molecules closely related chemically, i.e. vitamers) that is an essential micronutrient that an organism needs in small quantities for the proper functioning of its metabolism. Essential nut ...
,
mineral In geology and mineralogy, a mineral or mineral species is, broadly speaking, a solid chemical compound with a fairly well-defined chemical composition and a specific crystal structure that occurs naturally in pure form.John P. Rafferty, ed. ...
,
amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha ...
,
herb In general use, herbs are a widely distributed and widespread group of plants, excluding vegetables and other plants consumed for macronutrients, with savory or aromatic properties that are used for flavoring and garnishing food, for medicina ...
or other
botanical Botany, also called plant science (or plant sciences), plant biology or phytology, is the science of plant life and a branch of biology. A botanist, plant scientist or phytologist is a scientist who specialises in this field. The term "botany ...
, or dietary substance for use by humans 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.

Cholinergics

Some of the most widely used nootropic substances are the cholinergics. These are typically compounds and analogues of

choline Choline is an essential nutrient for humans and many other animals. Choline occurs as a cation that forms various salts (X− in the depicted formula is an undefined counteranion). Humans are capable of some ''de novo synthesis'' of choline but ...

Choline Choline is an essential nutrient for humans and many other animals. Choline occurs as a cation that forms various salts (X− in the depicted formula is an undefined counteranion). Humans are capable of some ''de novo synthesis'' of choline but ...

is an essential nutrient needed for the synthesis of

acetylcholine Acetylcholine (ACh) is an organic chemical that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Par ...

(a neurotransmitter), and phosphatidylcholine (a structural component of brain cell membranes). *

Citicoline Citicoline (INN), also known as cytidine diphosphate-choline (CDP-Choline) or cytidine 5'-diphosphocholine is an intermediate in the generation of phosphatidylcholine from choline, a common biochemical process in cell membranes. Citicoline is natu ...

- Compound consisting of choline and

cytidine Cytidine (symbol C or Cyd) is a nucleoside molecule that is formed when cytosine is attached to a ribose ring (also known as a ribofuranose) via a β-N1-glycosidic bond. Cytidine is a component of RNA. It is a white water-soluble solid. which is ...

. Several meta-analyses found that it is likely effective for improving memory and learning in older people with mild cognitive decline, as well as in people who are recovering from a stroke. There is little evidence it enhances cognition in young, healthy people. * Choline bitartrate - Choline bitartrate is a tartaric acid salt containing choline (41% choline by molecular weight). At least one meta-analysis has found choline bitartrate to be ineffective at improving any measure of cognitive performance. * Alpha-GPC - L-Alpha glycerylphosphorylcholine has thus far only been studied in the context of cognitive performance alongside other substances such as caffeine. A more comprehensive meta-analysis is needed before any strong conclusions are made about Alpha-GPC's usefulness as a nootropic.

Miscellaneous

Tolcapone Tolcapone, sold under the brand name Tasmar, is a medication used to treat Parkinson's disease (PD). It is a selective, potent and reversible nitrocatechol-type inhibitor of the enzyme catechol-''O''-methyltransferase (COMT). It has demonstrat ...

a systematic review noted that it improved verbal

and episodic

memory encoding Memory has the ability to encode, store and recall information. Memories give an organism the capability to learn and adapt from previous experiences as well as build relationships. Encoding allows a perceived item of use or interest to be conv ...

. *

Levodopa -DOPA, also known as levodopa and -3,4-dihydroxyphenylalanine, is an amino acid that is made and used as part of the normal biology of some plants and animals, including humans. Humans, as well as a portion of the other animals that utilize -DOPA ...

a systematic review noted that it improved verbal episodic memory and episodic memory encoding. *

Atomoxetine Atomoxetine, sold under the brand name Strattera, among others, is a medication used to treat attention deficit hyperactivity disorder (ADHD). It may be used alone or along with psychostimulants. It is also used as a cognitive enhancer to impr ...

may improve

and attention when used at certain doses. *

Desipramine Desipramine, sold under the brand name Norpramin among others, is a tricyclic antidepressant (TCA) used in the treatment of depression. It acts as a relatively selective norepinephrine reuptake inhibitor, though it does also have other activiti ...

may improve

and attention when used at certain doses. * Nicergoline may improve human cognitive performance, including concentration, psychomotor performance, attention, reaction times, and other indicators of brain function. * ISRIB enhanced spatial and fear-associated learning. The cognitive enhancing effects of

pramipexole Pramipexole, sold under the brand Mirapex among others, is medication used to treat Parkinson's disease (PD) and restless legs syndrome (RLS). In Parkinson's disease it may be used alone or together with levodopa. It is taken by mouth. Pramipe ...

guanfacine Guanfacine, sold under the brand name Tenex among others, is an oral medication used to treat attention deficit hyperactivity disorder (ADHD) and high blood pressure. Guanfacine is FDA-approved for monotherapy treatment of ADHD as well as being ...

clonidine Clonidine, sold under the brand name Catapres among others, is an α2-adrenergic agonist medication used to treat high blood pressure, ADHD, drug withdrawal ( alcohol, opioids, or nicotine), menopausal flushing, diarrhea, spasticity, an ...

, and fexofenadine have been tested, but no significant cognition-enhancing effects in healthy individuals were found.

Psychedelic microdosing Psychedelic microdosing is the practice of using sub-threshold doses ( microdoses) of serotonergic psychedelic drugs in an attempt to improve creativity, boost physical energy level, promote emotional balance, increase performance on problems-so ...

is the novel practice of using sub-threshold doses (microdoses) of

psychedelic drugs Psychedelics are a subclass of hallucinogenic drugs whose primary effect is to trigger non-ordinary states of consciousness (known as psychedelic experiences or "trips").Pollan, Michael (2018). ''How to Change Your Mind: What the New Science ...

in an attempt to improve mood and cognition. The efficacy of this has not been verified. In a study examining the qualitative reports of 278 microdosers the researchers found that there were mixed results among users. While some users reported positive effects such as improved mood and cognition, others paradoxically reported negative effects such as physiological discomfort and

anxiety Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil Turmoil may refer to: * ''Turmoil'' (1984 video game), a 1984 video game released by Bug-Byte * ''Turmoil'' (2016 video game), a 2016 indie oil tycoon video ...

. In one of the only double-blind, randomized studies to date, those given microdoses of

LSD Lysergic acid diethylamide (LSD), also known colloquially as acid, is a potent psychedelic drug. Effects typically include intensified thoughts, emotions, and sensory perception. At sufficiently high dosages LSD manifests primarily mental, vi ...

did not perform better than those given the placebo on cognitive tasks.

Herbs

*''

Bacopa monnieri ''Bacopa monnieri'' is a perennial, creeping herb native to the wetlands of southern and Eastern India, Australia, Europe, Africa, Asia, and North and South America. It is known by the common names water hyssop, waterhyssop, brahmi, thyme-leafed ...

'' is used in Ayurvedic traditional medicine to improve cognition. In 2019, the US

(FDA) warned manufacturers of

products containing ''Bacopa monnieri'' against making illegal and unproven claims that the herb can treat various diseases. * ''

Panax ginseng ''Panax ginseng'', ginseng, also known as Asian ginseng, Chinese ginseng, or Korean ginseng, is a species of plant whose root is the original source of ginseng. It is a perennial plant that grows in the mountains of East Asia. Names ''Panax gi ...

'' A review by the

Cochrane Collaboration Cochrane (previously known as the Cochrane Collaboration) is a British international charitable organisation formed to organise medical research findings to facilitate evidence-based choices about health interventions involving health profes ...

found that the results of its analysis "suggested improvement of some aspects of cognitive function, behavior and quality of life" but 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." * ''

Ginkgo biloba ''Ginkgo biloba'', commonly known as ginkgo or gingko ( ), also known as the maidenhair tree, is a species of tree native to China. It is the last living species in the order Ginkgoales, which first appeared over 290 million years ago. Fossils ...

'' An extract of ''Ginkgo biloba'' leaf is marketed in

form with claims it can enhance

in people without known cognitive problems, although there is no high-quality evidence to support such effects on memory or attention in healthy people. * ''

Salvia officinalis ''Salvia officinalis'', the common sage or just sage, is a perennial, evergreen subshrub, with woody stems, grayish leaves, and blue to purplish flowers. It is a member of the mint family Lamiaceae and native to the Mediterranean region, thoug ...

and lavandulaefolia'' (sage) Some research has suggested certain extracts of ''Salvia officinalis'' may have positive effects on human brain function, but due to significant

methodological In its most common sense, methodology is the study of research methods. However, the term can also refer to the methods themselves or to the philosophical discussion of associated background assumptions. A method is a structured procedure for bri ...

problems, no firm conclusions can be drawn. The

thujone Thujone () is a ketone and a monoterpene that occurs predominantly in two diastereomeric ( epimeric) forms: (−)-α-thujone and (+)-β-thujone. Though it is best known as a chemical compound in the spirit absinthe, it is unlikely to be respons ...

present in ''Salvia'' extracts may be

neurotoxic Neurotoxicity is a form of toxicity in which a biological, chemical, or physical agent produces an adverse effect on the structure or function of the central and/or peripheral nervous system. It occurs when exposure to a substance – specifical ...

. * ''

Centella asiatica ''Centella asiatica'', commonly known as gotu kola, kodavan, Indian pennywort and Asiatic pennywort, is a herbaceous, perennial plant in the flowering plant family Apiaceae. It is native to tropical regions of Africa, Asia, Australia, and islan ...

'' A 2017 meta-analysis with 11 studies (5 RCTs with placebo, 6 using other herbs as a comparison group) showing no significant improvement in all cognitive function, however may have some use in improving mood and anger. Overall dosages were smaller than the typical 3 grams used traditionally.

Nutrients and dietary supplements

A 2015 review found that use of

omega-3 fatty acid Omega−3 fatty acids, also called Omega-3 oils, ω−3 fatty acids or ''n''−3 fatty acids, are polyunsaturated fatty acids (PUFAs) characterized by the presence of a double bond, three atoms away from the terminal methyl group in their che ...

B vitamins B vitamins are a class of water-soluble vitamins that play important roles in cell metabolism and synthesis of red blood cells. Though these vitamins share similar names (B1, B2, B3, etc.), they are chemically distinct compounds that often coexis ...

, and

vitamin E Vitamin E is a group of eight fat soluble compounds that include four tocopherols and four tocotrienols. Vitamin E deficiency, which is rare and usually due to an underlying problem with digesting dietary fat rather than from a diet low in vitami ...

as nootropics was ineffective on cognitive function in normal middle-aged and older people. * Omega-3 fatty acids:

DHA DHA, Dha and dha may refer to: Chemicals * Docosahexaenoic acid, a 22:6 omega-3 fatty acid * Dehydroandrosterone, an endogenous androgenic steroid * Dehydroascorbic acid, an oxidized form of ascorbic acid * Dehydroacetic acid, a pyrone derivat ...

and

EPA The Environmental Protection Agency (EPA) is an independent executive agency of the United States federal government tasked with environmental protection matters. President Richard Nixon proposed the establishment of EPA on July 9, 1970; it be ...

two

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 found no cognition-enhancing effects in the general population. *

Folate Folate, also known as vitamin B9 and folacin, is one of the B vitamins. Manufactured folic acid, which is converted into folate by the body, is used as a dietary supplement and in food fortification as it is more stable during processing and ...

no cognition-enhancing effects in

middle-aged In the history of Europe, the Middle Ages or medieval period lasted approximately from the late 5th to the late 15th centuries, similar to the post-classical period of global history. It began with the fall of the Western Roman Empire ...

and older adults without folate deficiency. * Vitamin B₆ no cognition-enhancing effects in middle-aged and older adults without B6 deficiency. * Vitamin B₁₂ no cognition-enhancing effects in middle-aged and older adults without B12 deficiency. * Vitamin E no cognition-enhancing effects in middle-aged and older adults without vitamin E deficiency.

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* {{Authority control 1970s neologisms Amphetamine Methylphenidate