Neuroenhancement or cognitive enhancement is the experimental use of pharmacological or non-pharmacological methods intended to improve cognitive and affective abilities in healthy people who do not have a mental illness. [1] [2] Agents or methods of neuroenhancement are intended to affect cognitive, social, psychological, mood, or motor benefits beyond normal functioning.
Pharmacological neuroenhancement agents may include compounds thought to be nootropics, such as modafinil, [1] [3] caffeine, [4] [5] and other drugs used for treating people with neurological disorders. [6]
Non-pharmacological measures of cognitive enhancement may include behavioral methods (activities, techniques, and changes), [7] non-invasive brain stimulation, which has been used with the intent to improve cognitive and affective functions, [8] and brain-machine interfaces. [9]
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There are many supposed nootropics, most having only small effect sizes in healthy individuals. The most common pharmacological agents in neuroenhancement include modafinil and methylphenidate (Ritalin). Stimulants in general and various dementia treatments [10] or other neurological therapies [11] may affect cognition.
Neuroenhancement may also occur from:
Enhancers are multidimensional and can be clustered into biochemical, physical, and behavioral enhancement strategies. [17]
Approved for treating narcolepsy, obstructive sleep apnea, and shift work sleep disorder, modafinil is a wakefulness-promoting drug used to decrease fatigue, increase vigilance, and reduce daytime sleepiness. [1] Modafinil improves alertness, attention, long-term memory, and daily performance in people with sleep disorders. [1] [18]
In sustained sleep deprivation, repeated use of modafinil helped individuals maintain higher levels of wakefulness than a placebo, but did not help attention and executive function. [1] [19] Modafinil may impair one's self-monitoring ability; a common trend found in research studies indicated that participants rated their performances on cognitive tests higher than it was, suggesting an "overconfidence" effect. [1] [19]
Methylphenidate (MPH), also known as Ritalin, is a stimulant that is used to treat attention-deficit hyperactivity disorder (ADHD). MPH is abused by a segment of the general population, especially college students. [19]
A comparison between the sales of MPH to the number of people for whom it was prescribed revealed a disproportionate ratio, indicating high abuse. [19] MPH may impair cognitive performance. [20]
Studies are too preliminary to determine whether there are any cognitive-enhancing effects of agents such as memantine or acetylcholinesterase inhibitors (examples: donepezil, galantamine). [6]
Common drugs intended for neuroehancement are typically well-tolerated by healthy people. [6] [19] These drugs are already in mainstream use to treat people with different kinds of psychiatric disorders.
Assessment to determine potential adverse effects are drop-out rates and subjective rating. [6] [19] The drop-out rates were minimal or non-existent for donepezil, memantine, MPH, and modafinil. [6] [19] In the drug trials, participants reported the following adverse reactions to use of donepezil, memantine, MPH, modafinil or caffeine: [5] gastrointestinal complaints (nausea), headache, dizziness, nightmares, anxiety, drowsiness, nervousness, restlessness, sleep disturbances, and insomnia, [6] diuresis. [21] The side effects normally ceased in the course of treatment. [6] Various factors, such as dosage, timing and concurrent behavior, may influence the onset of adverse effects. [6] [19]
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Neurostimulation methods are being researched and developed. [8] Results indicate details of the stimulation procedures are crucial, with some applications impairing rather than enhancing cognition and questions being raised about whether this approach can deliver any meaningful results for cognitive domains. [8] Stimulation methods include electrical stimulation, magnetic stimulation, optical stimulation with lasers, several forms of acoustic stimulation, and physical methods like forms of neurofeedback. [8] [17]
Applications of augmented reality technologies may affect general memory enhancement, extending perception and learning-assistance. [22] [23] [ additional citation(s) needed ] The Internet may be considered a tool for enabling or extending cognition. [24] [25] [26] However, it is not "a simple, uniform technology, [n]either in its composition, [n]or in its use" and, as "an informational resource, currently fails to enhance cognition", partly due to issues that include information overload, misinformation and persuasion. [27]
Quality standards, validation and authentication, sampling and lab testing are commonly substandard or absent for products thought to be cognitive enhancers, including dietary supplements. [28] [29] [30] [31]
Neuroenhancement products or methods are used with the intent to:
Neuroenhancement products are mentioned in entertainment productions, such as Limitless (2011), which may to some degree probe and explore opportunities and threats of using such products. [35]
In general, people under the age of 25 feel that neuroenhancement agents are acceptable or that the decision to use them is to be made individually. [36] Healthcare officials and parents feel concerned due to safety factors, lack of complete information on these agents, and possible irreversible adverse effects; such concerns may reduce the willingness to take such agents. [37]
A 2024 study based on a representative sample of more than 20,000 adults in Germany showed that around 70% of those surveyed had taken substances with the aim of improving mental performance within a year, without a medical prescription. [38] The consumption of caffeinated drinks, such as coffee and energy drinks, was widespread (64% of users), expressly with the aim of improving performance, followed by dietary supplements and home remedies, such as ginkgo biloba (31%). [38] Around 4% stated that they had taken prescription drugs for cognitive enhancement (lifetime prevalence of 6%), corresponding to around 2.5 million users in Germany. [38]
A 2016 German study among 6,454 employees found a rather low life-time prevalence of cognitive enhancement prescription drug use (namely 3%), while the willingness to take such drugs was found in 10% of respondents. [39] A survey of some 5,000 German university students found a relatively low 30-day prevalence of 1%, while 2% of those sampled used such drugs within the last 6 months, 3% within the last 12 months, and 5% of others used the drugs over their lifetimes. [37] Of those students who used such substances during the last 6 months, 39% reported their use once in this period, 24% twice, 12% three times, and 24% more than three times. [37] Consumers of neuroenhancement drugs are more willing to use them again in the future due to positive experiences or a tendency towards addiction. [40]
Modafinil, sold under the brand name Provigil among others, is a wakefulness-promoting medication used primarily to treat narcolepsy. Modafinil is also approved for stimulating wakefulness in people with sleep apnea and shift work sleep disorder. It is taken by mouth. Modafinil is not approved by the US Food and Drug Administration (FDA) for use in people under age 17.
Stimulants are a class of drugs that increase the activity of the brain. They are used for various purposes, such as enhancing alertness, attention, motivation, cognition, mood, and physical performance. Some of the most common stimulants are caffeine, nicotine, amphetamines, cocaine, methylphenidate, modafinil.
Methylphenidate, sold under the brand names Ritalin and Concerta among others, is a potent central nervous system (CNS) stimulant used medically to treat attention deficit hyperactivity disorder (ADHD) and, to a lesser extent, narcolepsy. It is a primary medication for ADHD ; it may be taken by mouth or applied to the skin, and different formulations have varying durations of effect, commonly ranging from 2–4 hours. For ADHD, the effectiveness of methylphenidate is comparable to atomoxetine but modestly lower than amphetamines.
Nootropics, colloquially brain supplements, smart drugs and cognitive enhancers, are natural, semisynthetic or synthetic compounds which purportedly improve cognitive functions, such as executive functions, attention or memory.
A dopamine reuptake inhibitor (DRI) is a class of drug which acts as a reuptake inhibitor of the monoamine neurotransmitter dopamine by blocking the action of the dopamine transporter (DAT). Reuptake inhibition is achieved when extracellular dopamine not absorbed by the postsynaptic neuron is blocked from re-entering the presynaptic neuron. This results in increased extracellular concentrations of dopamine and increase in dopaminergic neurotransmission.
Donepezil, sold under the brand name Aricept among others, is a medication used to treat dementia of the Alzheimer's type. It appears to result in a small benefit in mental function and ability to function. Use, however, has not been shown to change the progression of the disease. Treatment should be stopped if no benefit is seen. It is taken by mouth or via a transdermal patch.
Dopamine receptors are a class of G protein-coupled receptors that are prominent in the vertebrate central nervous system (CNS). Dopamine receptors activate different effectors through not only G-protein coupling, but also signaling through different protein interactions. The neurotransmitter dopamine is the primary endogenous ligand for dopamine receptors.
Memantine, sold under the brand name Axura among others, is a medication used to slow the progression of moderate-to-severe Alzheimer's disease. It is taken by mouth.
Neurohacking is a subclass of biohacking, focused specifically on the brain. Neurohackers seek to better themselves or others by “hacking the brain” to improve reflexes, learn faster, or treat psychological disorders. The modern neurohacking movement has been around since the 1980s. However, herbal supplements have been used to increase brain function for hundreds of years. After a brief period marked by a lack of research in the area, neurohacking started regaining interest in the early 2000s. Currently, most neurohacking is performed via do-it-yourself (DIY) methods by in-home users.
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 was approved by the U.S. Food and Drug Administration (FDA) in June 2007. In 2016, the FDA granted Mylan rights for the first generic version of Cephalon's Nuvigil to be marketed in the U.S.
Human enhancement is the natural, artificial, or technological alteration of the human body in order to enhance physical or mental capabilities.
Performance-enhancing substances, also known as performance-enhancing drugs (PEDs), are substances that are used to improve any form of activity performance in humans. A well-known example of cheating in sports involves doping in sport, where banned physical performance-enhancing drugs are used by athletes and bodybuilders. Athletic performance-enhancing substances are sometimes referred to as ergogenic aids. Cognitive performance-enhancing drugs, commonly called nootropics, are sometimes used by students to improve academic performance. Performance-enhancing substances are also used by military personnel to enhance combat performance.
Lisdexamfetamine, sold under the brand names Vyvanse and Elvanse among others, is a stimulant medication that is used to treat attention deficit hyperactivity disorder (ADHD) in children and adults and for moderate-to-severe binge eating disorder in adults. Lisdexamfetamine is taken by mouth. Its effects generally begin within two hours and last for up to 14 hours. In the United Kingdom, it is usually less preferred to methylphenidate for the treatment of children.
Attention deficit hyperactivity disorder management options are evidence-based practices with established treatment efficacy for ADHD. Approaches that have been evaluated in the management of ADHD symptoms include FDA-approved pharmacologic treatment and other pharmaceutical agents, psychological or behavioral approaches, combined pharmacological and behavioral approaches, cognitive training, neurofeedback, neurostimulation, physical exercise, nutrition and supplements, integrative medicine, parent support, and school interventions. Based on a systematic literature review and meta analysis conducted in 2024, only FDA-approved medications and psychosocial interventions have been shown to improve core ADHD symptoms compared to control groups.
Pozanicline is a drug developed by Abbott, that has nootropic and neuroprotective effects. Animal studies suggested it useful for the treatment of ADHD and subsequent human trials have shown ABT-089 to be effective for this application. It binds with high affinity subtype-selective to the α4β2 nicotinic acetylcholine receptors and has partial agonism to the α6β2 subtype, but not the α7 and α3β4 subtypes familiar to nicotine. It has particularly low tendency to cause side effects compared to other drugs in the class.
Bromantane, sold under the brand name Ladasten, is an atypical psychostimulant and anxiolytic drug of the adamantane family related to amantadine and memantine which is used in Russia in the treatment of neurasthenia. Although the effects of the bromantane have been determined to be dependent on the dopaminergic and possibly serotonergic neurotransmitter systems, its exact mechanism of action is unknown, and it is distinct in its properties relative to typical psychostimulants such as amphetamine. Because of its unique aspects, bromantane has sometimes been described instead as an actoprotector.
PHA-543,613 is a drug that acts as a potent and selective agonist for the α7 subtype of neural nicotinic acetylcholine receptors, with a high level of brain penetration and good oral bioavailability. It is under development as a possible treatment for cognitive deficits in schizophrenia. It reduces excitotoxicity and protects striatal dopaminergic neurons in rat models. It also potentiates cognitive enhancement from memantine, decreases dynorphin release and inhibits GSK-B3.
S-18986 is a positive allosteric modulator of the AMPA receptor related to cyclothiazide. It has nootropic and neuroprotective effects in animal studies, and induces both production of BDNF and AMPA-mediated release of noradrenaline and acetylcholine in the hippocampus and frontal cortex of the brain.
Actoprotectors or synthetic adaptogens are compounds that enhance an organism's resilience to physical stress without increasing heat output. Actoprotectors are distinct from other performance-enhancing substances in that they increase physical and psychological resilience via non-exhaustive action. The term "actoprotector" is used to describe synthetic and isolated compounds possessing adaptogenic properties. By contrast, the term "adaptogen" is most often use to describe a natural herb as a whole, which can contain hundreds if not thousands of biologically active components.