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Neuroenhancement or cognitive enhancement refers to the targeted enhancement and extension of cognitive and affective abilities based on an understanding of their underlying neurobiology in
health Health, according to the World Health Organization, is "a state of complete physical, mental and social well-being and not merely the absence of disease and infirmity".World Health Organization. (2006)''Constitution of the World Health Organiza ...
y persons who do not have any
mental illness A mental disorder, also referred to as a mental illness or psychiatric disorder, is a behavioral or mental pattern that causes significant distress or impairment of personal functioning. Such features may be persistent, relapsing and remitti ...
. As such, it can be thought of as an umbrella term that encompasses pharmacological and non-pharmacological methods of improving cognitive, affective, and motor functionality, as well as the overarching ethico-legal discourse that accompanies these aims. Critically, for any agent to qualify as a neuroenhancer, it must reliably engender substantial cognitive, affective, or motor benefits beyond normal functioning in healthy individuals, whilst causing few side effects: at most at the level of commonly used comparable legal substances or activities, such as caffeine, alcohol, and sleep-deprivation. Pharmalogical neuroenhancement agents include the well-validated nootropics, such as citicoline, Bacopa monnieri and phosphatidylserine, as well as other drugs used for treating patients with
neurological disorder A neurological disorder is any disorder of the nervous system. Structural, biochemical or electrical abnormalities in the brain, spinal cord or other nerves can result in a range of symptoms. Examples of symptoms include paralysis, muscle weakn ...
s. Non-pharmacological measures include non-invasive brain stimulation, which has been employed to improve various cognitive and affective functions, and brain-machine interfaces, which hold much potential to extend the repertoire of motor and cognitive actions available to humans. Although consideration of individual neuroenhancement agents is usually triggered by success in clinical and technological fields, they have also been used to attempt to help people with lack of normal cognitive, motor, and affective abilities: for example, social skills and empathy. In this case, neuroenhancement drugs try to increase
oxytocin Oxytocin (Oxt or OT) is a peptide hormone and neuropeptide normally produced in the hypothalamus and released by the posterior pituitary. It plays a role in social bonding, reproduction, childbirth, and the period after childbirth. Oxytocin ...
and decrease
cortisol Cortisol is a steroid hormone, in the glucocorticoid class of hormones. When used as a medication, it is known as hydrocortisone. It is produced in many animals, mainly by the ''zona fasciculata'' of the adrenal cortex in the adrenal gland ...
levels helping people better their communication and social interaction skills.


Pharmacological


Modafinil

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 ...
is a wakefulness-promoting drug that decreases fatigue, increases vigilance, reduces daytime sleepiness, and improves mood. Modafinil is currently licensed for treating patients with disorders such as narcolepsy, sleep apnea, and
shift work sleep disorder Shift work sleep disorder (SWSD) is a circadian rhythm sleep disorder characterized by insomnia, excessive sleepiness, or both affecting people whose work hours overlap with the typical sleep period. Insomnia can be the difficulty to fall asleep ...
. This drug also seems promising in the treatment of depression and
bipolar disorder Bipolar disorder, previously known as manic depression, is a mental disorder characterized by periods of depression and periods of abnormally elevated mood that last from days to weeks each. If the elevated mood is severe or associated with ...
. Modafinil is currently being used by
United States Air Force The United States Air Force (USAF) is the air service branch of the United States Armed Forces, and is one of the eight uniformed services of the United States. Originally created on 1 August 1907, as a part of the United States Army Signal ...
personnel for missions of great duration in an attempt to decrease fatigue amongst aircrew. It has become more popular amongst the general public. In an online poll conducted by ''Nature'' magazine, 8.8% of 1400 corresponding readers admitted use of modafinil for non-medical reasons. Their reasoning behind its use was for increasing concentration and focus on a specific task or to counteract sleep deficit and jetlag. A comparison between the sales of modafinil to the number of patients revealed a disproportionate ratio, indicating high abuse. Modafinil has been reported to improve executive function in healthy non-sleep-deprived individuals, as well as potentially improving attention and learning and memory. Effects on sleep deprived individuals are even more striking: a single dose resulted in enhanced wakefulness, executive functions, and memory. In the case of sustained
sleep deprivation Sleep deprivation, also known as sleep insufficiency or sleeplessness, is the condition of not having adequate duration and/or quality of sleep to support decent alertness, performance, and health. It can be either chronic or acute and may vary ...
, repeated intake of modafinil helped individuals maintain higher levels of wakefulness than the
placebo A placebo ( ) is a substance or treatment which is designed to have no therapeutic value. Common placebos include inert tablets (like sugar pills), inert injections (like Saline (medicine), saline), sham surgery, and other procedures. In general ...
, but did not help attention and
executive function 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 succe ...
. Since the majority of these trials were conducted on military personnel, further research needs to be conducted on the effects of modafinil on the general population. 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 actually was, suggesting "overconfidence" effect. Modafinil is becoming increasingly popular among the general population. Apart from a consumer's want to increase his
neurological Neurology (from el, νεῦρον (neûron), "string, nerve" and the suffix -logia, "study of") is the branch of medicine dealing with the diagnosis and treatment of all categories of conditions and disease involving the brain, the spinal ...
performance, there are financial incentives for manufacturers as well. Modafinil has a market share of more than $700 million a year, indicating a high degree of off-label use. Modafinil is also one of the more easily available neuroenhancement drugs in the market today. Modafinil can be bought from many websites – mostly from Asian countries – as well as from
darknet market A darknet market is a commercial website on the dark web that operates via darknets such as Tor or I2P. They function primarily as black markets, selling or brokering transactions involving drugs, cyber-arms, weapons, counterfeit currency, stole ...
s. Modafinil first came into attention when world champion runner
Kelli White Kelli White (born April 1, 1977, in Oakland, California) is an American former sprinter. She won two gold medals in the World Championships in Paris in 2003. However, on June 18, 2004, she was stripped of her medals, because she tested positive ...
was tested positive for illegally consuming modafinil in the Athletics World Championship in 2003, resulting in the loss of her two gold medals.


Methylphenidate

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, ...
(MPH) is a
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 ...
that is used to treat attention-deficit hyperactivity disorder (ADHD). MPH is known to be highly abused by the general population, especially college students. In an online poll conducted by ''Nature'' magazine, 12.4% of 1400 corresponding readers admitted use of MPH for non-medical reasons. Their reasoning behind its use was for increasing concentration,
sleep deficit Sleep debt or sleep deficit is the cumulative effect of not getting enough sleep. A large sleep debt may lead to mental or physical fatigue, and can adversely affect one's mood, energy and ability to think clearly. There are two kinds of sleep d ...
, and
jetlag Jet lag is a physiological condition that results from alterations to the body's circadian rhythms caused by rapid long-distance trans-meridian (east–west or west–east) travel. For example, someone flying from New York to London, i.e. from ...
. A comparison between the sales of MPH to the number of patients revealed a disproportionate ratio, indicating high abuse. MPH is believed to have a positive effect for
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 ...
, but studies have not been able to conclusively verify this claim. Popular opinion that MPH enhances attention could not be verified. Studies of MPH have reported improved problem solving skills. However, when these studies were repeated to replicate the results, the placebo group scored higher, indicating that MPH may even impair performance. These inconclusive, and generally negative, results for
memory improvement Memory improvement is the act of enhancing one's memory. Memory deficits, age-related memory loss, and people's want to improve their own memory have led to research on how to best help people to improve their memory. Research has also worked to ...
are insufficient to explain the use of MPH for non-medical reasons. Users may have motives other than genuine neuroenhancement that propels its unprescribed use, such as subjective and recreational effects. The lack of any result, positive or negative, indicated that the 10–20 mg dosage may be too low for the drug. Further studies need to be conducted, looking at different doses of MPH.


Memantine

Memantine is a NMDA receptor antagonist and is used to treat patients with moderate to severe
Alzheimer's disease Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...
, but is also used as a neuroenhancement drug. Studies conducted on memantine were unable to conclusively verify neuroenhancement capability of the drug. Since most of these studies were single dose tests of memantine, it is possible that these drugs would only show some effect, positive or negative, after continuous intake. Until then, single dose studies of memantine are not enough to reveal the drug's actual potential.


Donepezil

Donepezil is an
acetylcholinesterase Acetylcholinesterase (HGNC symbol ACHE; EC 3.1.1.7; systematic name acetylcholine acetylhydrolase), also known as AChE, AChase or acetylhydrolase, is the primary cholinesterase in the body. It is an enzyme Enzymes () are proteins that a ...
inhibitor (AChEI) that is used to treat patients with mild to moderate Alzheimer's disease. While many AChEIs could be potential neuroenhancement substances, donepezil is the most commonly used AChEIs by the general population due to its widespread use for treating Alzheimer's disease. Most studies on donepezil are unable to conclusively verify the neuroenhancement capability of the drug. In such studies, it was seen participants that took donepezil scored higher than those that took the placebo. Donepezil helps individuals retain training tasks, verbal memory, and episodic memory. In sleep deprivation studies, while donepezil had no effect on well-rested patients, it had a positive effect on patients with 24 hours of sleep deprivation. Such patients benefited from increased memory performance and attention that would otherwise be deficit in such sleep-deprived conditions. However, this effect was only seen in individuals whose performance declined significantly due to sleep deprivation.


Non-pharmacological


Transcranial direct current stimulation

While neuroenhancement drugs are a potential method for cognitive performance enhancement,
Transcranial direct current stimulation Transcranial direct current stimulation (tDCS) is a form of neuromodulation that uses constant, low direct current delivered via electrodes on the head. It was originally developed to help patients with brain injuries or neuropsychiatric conditio ...
(tDCS) over the motor cortex (MC) is being seen as another potential method. Although it was originally intended to help patients with brain injuries such as stroke, there has been a lot of interest in the last few years on tDCS's capabilities for healthy individuals as well. Recent studies have already shown improved neuroplasticity from tDCS to facilitate motor learning in young humans, and it may be possible to apply this method to the older segment of the workforce as well. Stimulating higher cognitive functions of the brain, such as the language function, with tDCS in one study resulted in improved word retrieval. tDCS works by enhancing the connectivity in a given stimulated network, providing neural efficiency in highly specific brain areas critical for task performance. During this time,
fMRI Functional magnetic resonance imaging or functional MRI (fMRI) measures brain activity by detecting changes associated with blood flow. This technique relies on the fact that cerebral blood flow and neuronal activation are coupled. When an area o ...
images also showed reduced activity in the semantic retrieval processes, suggesting more efficient processing in task-critical areas of the brain. Reduced activity in circumscribed task-related areas has been attributed to consolidation of motor learning and superior memory performance. New research in tDCS is trying to localize the stimulation to affect the desired subset of highly specific task-relevant neurons.


Deep brain stimulation

Deep brain stimulation (DBS) is another form of neuroenhancement. Unlike tDCS, though, DBS involves the implantation of a medical device, and is restricted for use for only a few, severe diseases such as
Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...
and
dystonia Dystonia is a neurological hyperkinetic movement disorder in which sustained or repetitive muscle contractions result in twisting and repetitive movements or abnormal fixed postures. The movements may resemble a tremor. Dystonia is often inten ...
. In one study, DBS improved movement by 39%, reduced disability by 38%, and improved quality of life by 30% for patients with dystonia over a course of 3 months. The patients had a reduction in dystonia symptoms by 50%. Improvement was noticeable within hours to days after DBS application. The benefits of DBS as of now are far more than those of high-dosage
trihexyphenidyl Trihexyphenidyl (THP, benzhexol, trihex, marketed as Artane and others) is an antispasmodic drug used to treat stiffness, tremors, spasms, and poor muscle control. It is an agent of the antimuscarinic class and is often used in management of Pa ...
, a powerful drug used in the treatment for dystonia.


Side effects

Neuroenhancements drugs are well tolerated by healthy humans. These drugs are already in mainstream use to treat patients with different kinds of psychiatric disorders. Since most of the information on neuroenhancements and its capabilities are drawn from research experiments, the best way to determine adverse effects are drop-out rates and subjective rating. The drop-out rates were minimal or non-existent for donepezil, memantine, MPH, and modafinil. In the drug trials, participants reported the following adverse reactions to the consumption of donepezil, memantine, MPH, or modafinil:
gastrointestinal complaint Gastrointestinal diseases (abbrev. GI diseases or GI illnesses) refer to diseases involving the gastrointestinal tract, namely the oesophagus, stomach, small intestine, large intestine and rectum, and the accessory organs of digestion, the liver, g ...
s (nausea),
headache Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Headaches can occur as a result ...
,
dizziness Dizziness is an imprecise term that can refer to a sense of disorientation in space, vertigo, or lightheadedness. It can also refer to disequilibrium or a non-specific feeling, such as giddiness or foolishness. Dizziness is a common medical c ...
, nightmares,
anxiety Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil and includes feelings of dread over anticipated events. Anxiety is different than fear in that the former is defined as the anticipation of a future threat wh ...
, drowsiness, nervousness, restlessness, sleep disturbances, and
insomnia Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy, ...
. The side effects normally ceased in the course of treatment. Although there were no reported side effects from DBS, 18% of the patients reported device-related complications such as infections due to lead dislodgment or breakage.


Ethical, social and legal issues

Neuroenhancement is often seen analogous to the issue of
doping in sport In competitive sports, doping is the use of banned athletic performance-enhancing drugs by athletic competitors as a way of cheating in sports. The term ''doping'' is widely used by organizations that regulate sporting competitions. The use of ...
s. A common concern raised is an unfair advantage of people who consume enhancing drugs over people who don't. Many athletes, however, feel that the only way for them to win against athletes that take performance-enhancing drugs (PED) is for them to take PEDs as well; a similar thought process has developed within the general population in regard to people that consume neuroenhancement drugs. In a research study of 18- to 34-year-olds, 50% of them had little or no objection to the concept of doping. Students, in particular, often feel that cognitive neuroenhancers are acceptable. However, parents and healthcare providers are concerned about the safety and well-being of those that consume neuroenhancement. Generally, the moral acceptability (including fairness perceptions) of such substances for the purpose of neuroenhancement are an important factor in the decision to use or not use such drugs. Studies found that moral objections against such substances strongly decrease the willingness to use them. Neuroenhancement drugs play a key role in some recent novels and movies, such as ''Limitless'' (2011), probing and exploring the opportunities and threats of using neuro-enhancers in an imaginative way. In a recent article published by Jayne Lucke, the concept of neuroenhancement is compared to
sildenafil Sildenafil, sold under the brand name Viagra, among others, is a medication used to treat erectile dysfunction and pulmonary arterial hypertension. It is unclear if it is effective for treating sexual dysfunction in women. It is taken by ...
. The author states that "recreational users of ildenafilhad lower confidence in their ability to achieve an
erection An erection (clinically: penile erection or penile tumescence) is a physiological phenomenon in which the penis becomes firm, engorged, and enlarged. Penile erection is the result of a complex interaction of psychological, neural, vascular, ...
than non-users, even though they had significantly better erectile function. They become psychologically dependent on these drugs." The author believes a similar trend can be seen in neuroenhancement users. The author goes on to argue about how expectation, especially in students that are the general force, differs vastly on what is considered normal or good performance. Many argue that the only option for regulation of neuroenhancements is to allow it to everyone, thus minimizing cheating. Banning the drugs, on the other hand, may have detrimental consequences to society. Not only would it create a black market, amplifying issues caused by illicit use, it would also increase the cost to society from enforcing the law. Neuroenhancement drugs need to be assessed further for their merits and adverse effects, making it easier for policy makers to make a call on the regulation of such drugs.


Scope for cognitive enhancement

Proponents of cognitive enhancement have argued that there are vast potential benefits for the workforce, especially for the older segment. Due to advances in medical technology over the last century, the human life expectancy has increased significantly. Demographics for developed countries indicate rapid growth of the older segment of the workforce. Advancing age generally shows a pattern in the reduction of the ability to acquire new skills, but integration in the industry today requires employees to be able to acquire and retain new skills more than ever before.


Opinion


General public

The opinion of the general public on the issue of neuroenhancement is scattered. In general, the younger population under the age of 25 feel that neuroenhancements are acceptable or that the decision lies in the hand of that individual. Healthcare officials and parents feel concerned due to safety factors, lack of complete information on these drugs, and possible irreversible adverse effects. Such concerns have been shown to reduce the willingness to take such drugs. A recent German study among 6.454 employees found a rather low life-time prevalence of cognitive enhancement drug use (namely 2.96%), while the willingness to take such drugs was found in every tenth respondent (10.45%). Studies have estimated that between 7–9% of the college population in the United States consumes neuroenhancement drugs. Some studies estimate this figure to be as high as 12% or even 20%. A large-scale survey using a random sample of more than 5.000 German university students found a relatively low 30-days prevalence of 1.2%, 2.3% indicated the use of such drugs within the last 6 months, 3.2% within the last 12 months and during 4.6% during their lifetime, respectively. Of those students, who used such substances during the last 6 months, 39.4% reported their use once in this period, 24.2% twice, 12.1% three times and 24.2% more than three times. It has been shown that consumers of neuroenhancement drugs are much more willing to also use them in the future, e.g. due to positive experiences or a tendency towards addiction. Students primarily attribute consumption of these drugs for increased concentration, improved alertness, or to "get high". Neuroenhancement drug users rated the positive potential of neuroenhancement drugs higher than non-users, and rated the adverse effects of these drugs lower than non-users, showing more confidence in the result of these drugs. In a survey of 1324 German students, 32% of participants that do not consume neuroenhancement drugs felt they had positive cognitive effects while 12% felt they had a relaxation effect. In contrast, 54% of participants that do consume neuroenhancement drugs felt they had a positive cognitive effect while 25% felt they had a relaxation effect. The need to remain "alert" and "focused" can also been seen in the trend of caffeine consumption. The caffeine consumption for both students and the general population of the US is around 90%. Students who consume neuroenhancements also had a higher frequency of consuming
psychoactive A psychoactive drug, psychopharmaceutical, psychoactive agent or psychotropic drug is a chemical substance, that changes functions of the nervous system, and results in alterations in perception, mood, consciousness, cognition or behavior. Th ...
lifestyle drugs such as
cannabis ''Cannabis'' () is a genus of flowering plants in the family Cannabaceae. The number of species within the genus is disputed. Three species may be recognized: ''Cannabis sativa'', '' C. indica'', and '' C. ruderalis''. Alternatively ...
. This demonstrates a trend of psychological addiction amongst neuroenhancement users. A study among German university teachers (including professors) found a very low prevalence of neuroenhancement drug use. Only 0.9% of the respondents reported the use of such drugs. However, 10% of the respondents are willing to take such drugs in the future, what might indicate a potential increase of the prevalence. One reason to use such drugs was work-related stress.


Physicians

Physicians play an important role in determining the potential abuse of neuroenhancing drugs. While some neuroenhancing drugs do not require a prescription and are easily available, others that require prescription are up to the discretion of the physician. In a survey conducted among Swiss psychiatrists and general practitioners, the majority of surveyed physicians agreed that their criteria to determine whether or not a dysfunction should be considered a disease is if the patient indicates subjective suffering and/or negative consequences for everyday ability to work. The surveyed physicians, however, were in majority agreement that they do not prescribe medication without a clear indication of such a dysfunction.


See also

* Cognitive liberty * Evidence-based learning *
List of drugs used by militaries Militaries worldwide have used or are using various psychoactive drugs to improve performance of soldiers by suppressing hunger, increasing the ability to sustain effort without food, increasing and lengthening wakefulness and concentration, suppr ...
* Intelligence amplification


References


Further reading

* * * * {{Authority control * Transhumanism