neuroenhancement neuroenhancement 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 healthy persons who do not have any mental illness and outcomes in experimental research. as such, it can be thought of as an umbrella term that encompasses pharmacological and non-pharmacological methods of improving neurological functionality, especially interventions designed to improve human form or functioning beyond what is necessary to sustain or restore good health, as well as the overarching ethico-legal discourse that accompanies these aims and practices. neuroenhancers reliably engender substantial cognitive, social, psychological, mood, or motor benefits beyond normal functioning in healthy individuals, whilst causing few side effects, albeit broader definitions also include the use of psychoactive substances that are deemed unhealthy or have substantial side effects. pharmacological neuroenhancement agents include well-validated nootropics, such as modafinil, bacopa monnieri, phosphatidylserine, and caffeine, as well as other drugs used for treating patients with neurological disorders. non-pharmacological measures of cognitive enhancement include behavioral methods (activities, techniques, and changes), 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 capacities. pharmacological pubmed search results for studies and reviews with "nootropic" or "smart drug" in the title or abstract; many relevant studies are not in pubmed and some included are not mainly about nootropics. there are many nootropics, which include smart drugs and dietary supplements, and all or many of these are relevant to neuroenhancement, albeit many or most only have small effect sizes in healthy individuals or common major side effects. the most common, popular or notable pharmacological agents in neuroenhancement with potentials for significant effect sizes (as in at least as effective or similar to caffeine) include modafinil and methylphenidate (ritalin). stimulants in general and various antidementives, anxiolytics, empathogens, types of microdosing (mainly of psychedelics), and antidepressants may also fall into the scope of neuroenhancement despite not necessarily being considered nootropics. 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 a lack of normal cognitive, motor, and affective abilities: for example, social skills and empathy. in this case, neuroenhancement drugs try to increase oxytocin and decrease cortisol levels helping people better their communication and social interaction skills. neuroenhancement is not only concerned with, short- and longer-term, enhancement of intelligence (by various types of measures), learning (e.g. general memory enhancement), focus/flow-state, and related cognitive domains or measures but also: mood ('mood enhancement') motivation ('motivation enhancement'; e.g. apathy-related, in goal-setting, will to power, anhedonia or for exercise) task-enjoyment sociability (e.g. talking-related or empathy) substituting and/or ending unhealthy substances use (substance use disorders or low/moderate consumption) discipline or will-power and self-control creativity cognitive endurance (cognitive work endurance and fatigue resistance) specific capacities and skills such as verbal fluency, types of problem-solving, reasoning, simple and complex reaction time, and so on psychological resilience and more enhancers are multidimensional and can be clustered into biochemical, physical, and behavioral enhancement strategies. n-acetylcysteine (nac) is an example of a low side effects cognitive enhancer relevant to both unhealthy substance use change and mood stabilization. modafinil main article: modafinil 3d structure of modafinil pubmed search results for "modafinil" in title or abstract modafinil 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. this drug also seems promising in the treatment of depression and bipolar disorder. modafinil is currently being used by united states air force 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, repeated intake of modafinil helped individuals maintain higher levels of wakefulness than the placebo, but did not help attention and executive function. 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 was, suggesting an "overconfidence" effect. modafinil is becoming increasingly popular among the general population. apart from a consumer's want to increase his neurological 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 markets. modafinil first came into public attention when world champion runner kelli white was tested positive for illegally consuming modafinil in the athletics world championship in 2003, resulting in the loss of her two gold medals. for research comparing modafinil with similar compounds, investigating combinations and showing trade-off type issues, see #research topics below. methylphenidate 3d structure of methylphenidate methylphenidate (mph), also known as ritalin, is a stimulant 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, and jetlag. 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 on memory consolidation, 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 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 an nmda receptor antagonist and is used to treat patients with moderate to severe alzheimer's disease, 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 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 who 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 a deficit in such sleep-deprived conditions. however, this effect was only seen in individuals whose performance declined significantly due to sleep deprivation. research and candidates studies about neuroenhancement: pubmed search results for a query (for titles and abstracts) research also explores derivatives of already existing cognitive enhancers that have or could have higher bioavailability, such as n-acetylcysteine amide for nac and other bioavailability-enhancing strategies. another approach to enhance efficacy, potency or selectivity that is relevant to medications in general is improving drug delivery, including enabling additional routes of administration such as via nanoemulsions for "nose-to-brain" drug delivery or hypothetically via brain implants. differential half-lives may also be a topic of research and development. modafinil substantially increases alertness but, having a long half-life of approximately 13 hours, can delay or impair sleep-onset, with there being no marketed shorter-acting version. according to two 2009 studies, armodafinil is eliminated approximately three times more slowly than the s-isomer of racemic modafinil. research may also investigate: general safety and efficacy in healthy people in particular as well as for long-term use and also using neuroimaging (and associated brain mapping and neuroimaging intelligence testing) studies may also measure impacts of regular consumption of chemicals like modafinil on mortality and lifespan in animal models, such as short-lived mice. different protocols (e.g. dosages, timing and scheduling) combinations (e.g. concurrent, cyclic or sequential and precursors, depletions and cofactors) one common combination under research is the concurrent combination of l-theanine with caffeine. one study investigated high-dosage modafinil combined with low-dosage caffeine – 200 mg of each. there are also studies combing different types of cognitive enhancers such as biochemical and behavioral enhancers such as modafinil combined with meditation. the multinutrient intervention of uridine combined with choline (cdp-choline or e.g. in eggs) and omega 3 (e.g. in fish) has synergy, improving some measures of cognition and mood better. factors of effects outcomes (including situational, task-difficulty, personal (e.g. genetic or baseline-skill-levels), protocol-related, etc) interactions (e.g. polypharmacy and combinations) trade-off-type issues modafinil can, depending on various factors, at or around the time of consumption: impair sleep due to its long half-life (