The enhancement use of neuropharmaceuticals: more scepticism and caution needed


There is weak evidence that neuropharmaceuticals are widely used for neuroenhancement, doubts about whether these substances enhance real world cognitive performance in normal subjects, and few studies of their safety or efficacy in regular sustained use. More scepticism is needed about neuroenhancement claims for pharmaceuticals and we need to avoid normalizing such use by inflating its prevalence.

Some influential neuroethicists have argued that it is ethically permissible for normal healthy adults to use neuropharmaceuticals to enhance ‘cognitive or neural functioning’[1]. Some claim that drugs such as Modafinil and methylphenidate are already used widely in this way [2]. Others have provided advice to prescribers on how to respond to requests from healthy adults for such drugs [3]. An influential group has argued that pharmaceutical companies should be allowed to market drugs for enhancement purposes, with appropriate regulation [1]. We think that historical experience with drugs of dependence indicates that more scepticism is needed about these claims. We should be cautious in adopting the policies proposed.


The main evidence that neuroenhancement is widespread (apart from case reports of users known to the authors, e.g. [2]) comes from survey data on college students' use of stimulant drugs to improve their grades [1]. Contrary to assertions, these data do not indicate that enhancement use of stimulants is widespread among US college students. In a recent review of nationally representative US surveys, widely differing estimates (from 1.5% to more than 31%) indicate problems of consistency of methods and representativeness of samples. Larger, more representative studies report single-digit figures on recent use, with the largest such study reporting a figure of 3% [4]. Users were more likely to be white males with lower grades who also used other illicit substances. A recent survey found that 6% of 3639 US undergraduates at a large US university reported non-medical use of prescription stimulants in the last year, but only 1% had used 10 or more times and only 2% had done so in the last month [5].


There is very weak evidence that putatively neuroenhancing pharmaceuticals in fact enhance cognitive function. A recent report from the British Academy of Medical Sciences concluded that there was very limited evidence for cognitive enhancement in healthy individuals and effects on vigilance, verbal learning and long-term memory were small under laboratory conditions [6]. It is uncertain whether effects in laboratory tests translate into benefits in everyday life, especially when these drugs are used regularly over extended periods [7]. It is also unclear whether people who function well obtain much benefit or whether increased performance in one cognitive domain is at the cost of deficits in others [8]. Discriminating enhancement effects on cognitive performance from placebo effects is a special challenge, because these drugs may increase confidence without necessarily improving cognitive skills, and expectations may influence the apparent effects of a drug [9].


Three doubtful assumptions underpin the proposal that pharmaceutical companies should be allowed to market cognitive enhancing drugs to healthy adults, provided that they meet regulatory standards for safety and efficacy. The first assumption is that these regulations are effective in ensuring that existing pharmaceutical drugs are safe and effective for therapeutic use. Secondly, they assume that it will be relatively straightforward to assess the safety and efficacy of drugs used for neuroenhancement [10]. Thirdly, they assume that pharmaceutical companies will be interested in submitting putative cognitive enhancers for regulatory approval.

Assessing safety

Drug regulators have limited information on which to make decisions about the safety of therapeutic drugs. Clinical trials often enrol only patients without comorbid conditions and assess drugs over weeks or months, rather than years or decades. There is consequently limited information about how well a drug works in more diverse populations, when used in combination with other drugs and without medical supervision. Adverse effects often become apparent only after large numbers of patients have used a drug for long periods of time, as happened recently in the case of Vioxx, which was recalled from sale in 2004 after being found to increase the risk of heart attack.

Ritalin has been used for more than 60 years in treating adults, adolescents and children, and no cases of Ritalin addiction have been described in children under the age of 13 years [11]. Nevertheless, this drug suppresses appetite and causes insomnia, and delays growth in children. There is also little information on its long-term safety in adults or children [12]. The level of harm that may arise from neuroenhancement use of this drug in older adults at increased risk of cardiovascular is unclear.

The assessment of dependence potential is essential when regulating drugs that may be used for enhancement use. Ritalin is subject to legal controls because of the widespread recreational use and abuse of methylphenidate in Sweden in the 1960s [12]. Users who take the drug in accordance with medical guidelines do not report euphoria, but regular use of larger doses can produce dependence [12].


The use of stimulant drugs is assumed widely to make one smarter, but there is very little evidence that these drugs improve school performance in children with attention-deficit hyperactivity disorder (ADHD) [13]. While these drugs improve focus and concentration, and thereby improve performance in class, this has not been shown to translate into improved school grades.

The suggestion that medical professionals can assess the effectiveness of psychotropic neuroenhancement drugs in individual patients to whom they prescribe them is implausible [3,14]. It is highly unlikely that busy physicians have the time or the skill to make informed judgements about the effectiveness of drugs in individual cases when it is difficult to discriminate between drug and placebo effects in large randomized controlled trials.

Regulatory approval for enhancement use

It is doubtful that pharmaceutical companies will seek regulatory approval for enhancement use of drugs. Such use is most likely to be off-label use of drugs approved for therapeutic purposes. Given the expense of obtaining regulatory approval, pharmaceutical companies will have little incentive to conduct trials on or seek approval for off-label use of these drugs. Doctors who prescribe these drugs-off label do so at their own risk, so companies can profit from such use without incurring any legal liability for adverse effects arising from it. It is even less likely that companies would apply for regulatory approval for drugs that would be used solely for enhancement purposes. Under any defensible regulatory system, the requirements would have to be much higher to establish the safety of a drug that would be used in healthy adults.


Contemporary advocates of neuroenhancement speak as if this was a wholly novel phenomenon. They fail to appreciate the relevance of historical experiences with the non-medical use of what are recognized nowadays as drugs of addiction [15]. Cocaine, for example, was arguably one the first pharmaceutical drugs that was promoted as a cognitive enhancer, by Sigmund Freud among others [16]. It was seen as a low-risk drug that could be taken regularly to relieve tiredness, increase endurance and improve cognitive performance [17].

Amphetamines were viewed in much the same way from the 1930s and into the 1970s [18]. Students used amphetamines to cram for examinations, and pharmaceutical companies claimed that they enhanced ‘mental performance’[18]. Further studies showed that they improved efficiency in simple mental and psychomotor tasks largely because they increased confidence [18]. By the late 1960s amphetamines were used on US university campuses as a study aid and a party drug in much the same way that it is claimed nowadays that students use Ritalin [11]. Both drug classes were placed under legal control because of the high rates of dependence and adverse effects experienced by regular users [17,18].


There is weak evidence for the widespread enhancement use of neuropharmaceuticals. There are also doubts about whether using these substances enhances real-world cognitive performance in normal subjects. There are very few studies assessing their safety or efficacy in regular use over sustained periods. Guidelines for enhancement prescription are accordingly premature. More scepticism needs to be expressed about neuroenhancement claims for pharmaceuticals and bioethicists should be much more cautious in normalizing such use by inflating estimates of its prevalence or making proposals that will facilitate such use.

Declarations of interest

Jayne Lucke has recently been awarded an ARC Linkage Grant, which involves some cash and in-kind support from Bayer Australia.