Neuroenhancement

3D structure of modafinil

Modafinil is a wakefulness-promoting drug that decreases fatigue, increases vigilance, reduces daytime sleepiness, and improves mood.[4][5][10] Modafinil is currently licensed for treating patients with disorders such as narcolepsy, sleep apnea, and shift work sleep disorder.[2][5] This drug also seems promising in the treatment of depression and bipolar disorder.[5] 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.[2] A comparison between the sales of modafinil to the number of patients revealed a disproportionate ratio, indicating high abuse.[2]

Modafinil has been reported to improve executive function in healthy non-sleep-deprived individuals, as well as potentially improving attention and learning and memory.[11] Effects on sleep deprived individuals are even more striking: a single dose resulted in enhanced wakefulness, executive functions, and memory.[10] 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.[2][10] 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.[2]

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.[4] 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.[4][12][13] Modafinil first came into 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.[4]

3D structure of methylphenidate

Methylphenidate (MPH) 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.[2][4] 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.[2]

A comparison between the sales of MPH to the number of patients revealed a disproportionate ratio, indicating high abuse.[2] MPH is believed to have a positive effect for memory consolidation, but studies have not been able to conclusively verify this claim.[2][10] Popular opinion that MPH enhances attention could not be verified.[2][10] 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.[4]

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.[2] The lack of any result, positive or negative, indicated that the 10–20 mg dosage may be too low for the drug.[2] Further studies need to be conducted, looking at different doses of MPH.[2][10]

Memantine structure

Memantine is a NMDA receptor antagonist and is used to treat patients with moderate to severe Alzheimer's disease, but is also used as a neuroenhancement drug.[3] 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.[3]

10mg donepezil pill

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.[3]

Most studies on donepezil are unable to conclusively verify the neuroenhancement capability of the drug.[3] 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.[3] 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.[3] However, this effect was only seen in individuals whose performance declined significantly due to sleep deprivation.[3]

While neuroenhancement drugs are a potential method for cognitive performance enhancement, Transcranial direct current stimulation (tDCS) over the motor cortex (MC) is being seen as another potential method.[14] 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.[14]

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.[15] During this time, fMRI images also showed reduced activity in the semantic retrieval processes, suggesting more efficient processing in task-critical areas of the brain.[15] 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.[15]

Illustration showing an electrode placed deep seated in the brain

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 and dystonia.[16] In one study, DBS improved movement by 39%, reduced disability by 38%, and improved quality of life by 30% for patients suffering from dystonia over a course of 3 months.[16] The patients had a reduction in dystonia symptoms by 50%.[16] 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, a powerful drug used in the treatment for dystonia.

The opinion of the general public on the issue of neuroenhancement is scattered.[17][22] 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.[17] Such concerns have been shown to reduce the willingness to take such drugs.[23][24][19]

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%).[25] 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%.[22] 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.[23] 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.[20][26] Students primarily attribute consumption of these drugs for increased concentration, improved alertness, or to "get high".[17][22] 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.[22] 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.

A table for the results of a survey conducted on physicians

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%.[22][27] Students who consume neuroenhancements also had a higher frequency of consuming psychoactive lifestyle drugs such as cannabis. This demonstrates a trend of psychological addiction amongst neuroenhancement users.[22]

A study among German university teachers (including professors) found a very low prevalence of neuroenhancement drug use.[20] 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 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.[6] The surveyed physicians, however, were in majority agreement that they do not prescribe medication without a clear indication of such a dysfunction.[6]