Academic Doping Or Viagra for the Brain?

outlookoutlook Academic doping or Viagra for the brain?

The history of recreational drug use and pharmacological enhancement can provide insight into these uses of neuropharmaceuticals Jayne C. Lucke, Stephanie K. Bell, Bradley J. Partridge & Wayne D. Hall

ecent developments in neuroscience Nature readers (Maher, 2008) seems to sup- of cognitive enhancers was extremely low, have raised the possibility that port claims that neuroenhancement is quite and that the idea of healthy people taking Rneuropharmaceuticals and other common. One in five respondents stated a drug to improve their cognitive capability interventions could be used to enhance that they had used drugs for non-medical was new to most participants (Academy of brain processes in ‘normal’ people who are reasons to stimulate their focus, concen- Medical Sciences, 2008). Despite the pro not impaired by mental illness or disorder. tration or memory: 62% had used methyl- bably low prevalence of neuroenhancer The terms ‘cognitive enhancement’ and phenidate, 44% had used modafinil and use in the population, media coverage has ‘neuroenhancement’ are often used inter- 15% had used beta-blockers such as pro- nonetheless suggested that it is widespread, changeably to describe this type of drug pranolol. This was, however, an informal and that we will soon need a ‘doping test’ use—which is similar to doping in sports— survey by Nature, not a scientific study, and for university exams. Such coverage might that is not for treating impairments of its purpose was to stimulate debate, rather unintentionally raise awareness of and clinical significance or for recreation. than to estimate the prevalence of neuro increase interest in neuroenhancement enhancement in the general population. among the general public. The popularity of Drug misuse studies have Similarly, there is anecdotal evidence of the ‘lifestyle drugs’—particularly those aimed not, therefore, provided use of modafinil to treat the adverse effects at delaying the effects of ageing—suggests of jet-lag among academics. that there might also be a potential market good evidence of widespread for neuroenhancers. There are many over- neuroenhancement mpirical surveys about the misuse of the-counter dietary supplements, and other prescription stimulants are often cited substances such as ginkgo biloba, that are There is some evidence that drugs such as evidence that neuroenhancement marketed as being able to improve cognitive ® E as methylphenidate (Ritalin ) and modafinil has become common (Wilens et al, 2008). function, despite there being no evidence (Provigil®) can enhance cognition to a small However, these data probably overestimate for their efficacy. Moreover, research to degree in people without cognitive defi- the extent of neuroenhancement, as the develop treatments and preventative thera cits, but there are important caveats to this. use of a drug without a doctor’s prescrip- pies for Alzheimer disease and other cog- Drugs that enhance one type of function tion might be not only for enhancement, nitive impairments might actually lead to might have a detrimental impact on another, but also for recreation, addiction and self- the development of neuroenhancing drugs or people who already function well might medication. Even if we assume that most that people without cognitive impairment not experience any benefit, whereas those stimulant misuse is for the purpose of neuro could use. with less natural ability might experience enhancement, there is no evidence from only modest effects. Another important issue drug misuse studies that it is a widespread The popularity of ‘lifestyle is whether statistically significant improve- problem: recent and regular use of stimu- ments in cognitive functioning can be trans- lants without a doctor’s prescription is usu- drugs’ […] suggests that there lated into practical or clinically significant ally found to be low—for example, as few as might also be a potential market benefits in real-world contexts. 2% report using the drug in the past month for neuroenhancers Notwithstanding these caveats, some (Teter et al, 2010). Drug misuse studies have proponents of neuroenhancement specu- not, therefore, provided good evidence of Three questions are pertinent for the late that it will soon become normal prac- widespread neuroenhancement. public debate about neuroenhancement. tice (Greely et al, 2008). However, such In fact, there is little empirical evidence Should it be regarded as a form of cheating? speculation is supported by limited evi- for neuroenhancement (Lucke et al, 2010). Should it be regarded as a limited exten- dence of the prevalence of the use of neuro A recent public engagement exercise in the sion of medical treatment or as a legitimate enhancers. For example, an informal poll of UK concluded that the public’s awareness lifestyle enhancement? What should we do

about it? In this article, we consider pos- A common concern about the high-school children (Carpenter, 2007). sible answers to these questions by com- use of drugs to improve physical At the elite sporting level, the US Office of paring neuroenhancement with two other National Drug Control Policy estimates that forms of enhancement: doping in sport or cognitive performance is that between 10 and 90% of all athletes use dop- and the enhancement of sexual perfor it gives an unfair advantage to ing, depending on the sport. This wide range mance using drugs that were developed to those who take the drug over reflects the level of uncertainty about its treat erectile dysfunction, such as sildenafil those who do not prevalence (Holt et al, 2009). (Viagra®)—we will refer to these as ‘Viagra’ Viagra is a selective inhibitor of phospho for simplicity. These comparisons might regularly performed to enforce the rules diesterase type 5 (PDE5). It was developed provide instructive examples of possible (Schermer, 2008). by Pfizer and approved in 1998 for the societal responses to neuroenhancement. Yet, the extent to which doping occurs in treatment of erectile dysfunction, which is Performance enhancement in sport is pro- sport is difficult to estimate. Its prevalence associated with ageing and other medical hibited and there are well-established probably depends on the type of sport, the conditions, and which can have a profound procedures for testing and enforcing com- success of drugs in enhancing performance, impact on sexual relationships. One-half of pliance, whereas sexual enhancement using the age of the athlete, the level of competi- all males over 40 years of age might expe- Viagra is regulated through the health-care tion and how professionalized is the sport, rience erectile dysfunction at some time system; drugs are available on prescription among other factors. The use of performance- (Jackson et al, 2005). Viagra was considered from a doctor or at pharmacies and they are enhancing drugs is not limited to elite ath- a breakthrough in its treatment and efforts publicly funded in some countries. letes; it extends to amateur competitors have been made to extend its use to female including college students and school chil- sexual dysfunction, premature ejaculation oping in sport is defined as “the dren. Specific sports such as weight-lifting and cardiovascular dysfunctions (Jackson employment of prohibited means have seen a high prevalence of drug use: et al, 2005). Dto enhance performance, with the 1999 uS Powerlifting Federations’ As with many new drugs, there was the intention to gain competitive advan- National Championship found that 55% of much optimism among the medical com- tage over the opponent” (Petroczi, 2007). competitors reported using steroids in the munity and the general public, facilitated The World Anti-Doping Agency, estab- previous 12 months (Carpenter, 2007). In by extensive media attention, about the lished in 1999, oversees the global gover the UK it has been claimed that steroids are potential value of Viagra. By 2005, Viagra nance of sports doping. There are lists of commonly offered to children and growth had proven to be safe and effective in treat- forbidden substances and drug tests are hormones have been tried by up to 5% of ing erectile dysfunction that resulted from

many causes with a variety of co-morbid …young people might use A study in the 1990s that asked athletes medical conditions. More than 700,000 cognitive enhancers or about their willingness to use performance- doctors have prescribed Viagra and more recreational drugs because they enhancing drugs found a pervasive ‘win than 23 million men are reported to have at all costs mentality’ (Ehrnborg & Rosen, used it (Jackson et al, 2005). It has also believe that others are doing 2009). Of the athletes, 98% said that they been found to lead to a significant improve- so and that they must do so to would take a performance enhancer if they ment in erectile function, self-esteem and remain competitive would not be caught. One-half said that sexual satisfaction in men without erec- they would use a performance enhancer if tile dysfunction, and to enhance the sex measured against each other in examinations they would win every competition for the lives of middle-aged men without erectile might be seen as being in competition, but it next five years, even if they could die from problems (Gruenwald et al, 2009). is not clear whether a medical resident who the side effects (Ehrnborg & Rosen, 2009). takes modafinil to increase alertness during Public attitudes toward the use of neuro uch debate in the bioethical lit- a long shift is in competition with fellow resi- enhancing drugs are less clear. There is some erature is about whether neuro dents. If the drug increases alertness, does evidence suggesting that although health- Menhancement is a form of cheating. this disadvantage non-enhanced residents? care providers and parents are reluctant Cheating is the violation of an explicit rule— Even without competition, the perception to condone the practice, students are less as in sports doping—or implicit rules, such as that others are using cognitive-enhancing concerned about long-term health effects social norms or codes of conduct (Schermer, drugs might lead to cognitive enhancement (DeSantis & Hane, 2010). For example, stu- 2008). A common concern about the use of becoming a requirement for the job. dents using illegal stimulants justified their drugs to improve physical or cognitive per- Athletes who believe that most of their use as a way of achieving good marks; they formance is that it gives an unfair advantage competitors are doping might think that they either believed that moderate use would not to those who take the drug over those who can only win with the assistance of perform- harm them, that they were self-medicating do not. This concern might have less salience ance enhancers. This could create indirect for undiagnosed symptoms, or they equated in cognitive enhancement than in sporting pressure to use drugs, regardless of personal stimulant use with drinking coffee (DeSantis enhancement, because there is so far little concerns about their use. Similarly, young & Hane, 2010). evidence that drugs significantly enhance people might use cognitive enhancers or cognitive performance (Outram, 2010). recreational drugs because they believe Many regard taking drugs for Nonetheless, this perception of unfairness that others are doing so and that they must neuroenhancement as a lifestyle remains (Cakic, 2009). do so to remain competitive (Cakic, 2009). choice, similar to the non- These processes illustrate a common theme …individuals using in explanations of why athletes engage in medical use of Viagra, which neuroenhancement are aiming sports doping: subjective norms (Petroczi, is considered one of the first to achieve something without 2007). People’s beliefs about the drug use of lifestyle drugs their peers have a large impact on their own effort […] and that this therefore willingness to use those drugs. This makes it Schermer (2008) suggests that neuro diminishes the value of their important not to exaggerate the prevalence enhancement is different from sports dop- achievement of a harmful behaviour. ing because there are no explicit rules that prohibit it in examinations. However, many There is another perspective on this, lthough performance enhancement people have a moral intuition that there namely that individuals using neuro in sport is widely condemned by the is something wrong with it, which would enhancement are aiming to achieve Amedia, sporting officials and govern- require a ban on such drug use (Sabini & something without effort—regardless of ment bodies, factors such as prize money, Monterosso, 2005). One option would whether it involves competition—and that sponsorship, widespread coverage of sport- be to allow everyone access to enhanc- this therefore diminishes the value of their ing events and a desire to win encourage ers to minimize cheating. If the process achievement. It is misleading to think that doping at all levels of competition (Holt et al, of education is about gaining cognitive neuroenhancement might obviate the need 2009). Athletes still engage in doping and skills that can be used in the workplace for hard work or study; it is unlikely that there is evidence that at least some mem- rather than to perform in exams (Schermer, drugs will produce a good exam mark if the bers of the general public are not concerned 2008), we need to consider the social subject has not studied. Instead, drugs might by the practice. Recent studies suggest that consequences of neuroenhancement in make the time spent studying more enjoy- young people do not hold extremely nega- a broader context, beyond its impact on a able or efficient, and these effects might be tive views of doping, unlike sporting bodies particular examination. more marked in those of lower ability. If this and governments. In one study, more than was the case, those who are less disciplined 50% of 18–34-year-old sporting fans had any regard taking drugs for or intelligent might gain an advantage from ‘little or no objection’ to doping and 19% neuroenhancement as a life- using drugs in conjunction with extra study. were in favour of legalizing it under medi- Mstyle choice, similar to the non- Individuals who take cognitive-enhancing cal supervision (Morgan, 2009). Other medical use of Viagra, which is considered drugs would potentially have a competitive evidence suggests that students who take one of the first lifestyle drugs. The effects, advantage, but this in itself assumes that they stimulants regard cognitive enhancement as predictably, include higher levels of sexual are in competition. College students who are acceptable (DeSantis & Hane, 2010). satisfaction as well as improvements in

emotional well-being and mental health Similar concerns could also arise among different types of regulation, as might differ- (Salonia et al, 2003). regular users of neuroenhancing drugs; they ent uses of the same substances. Larriviere There were initial concerns there would might lose confidence in their ability to do et al (2009) have recently provided guid- be excessive demand for Viagra for both well without medication. ance for neurologists on how to respond to therapeutic and ‘lifestyle’ uses, that doc- Some have argued that there is no clear requests for neuroenhancers, assuming that tors would be inundated with requests, and line between treatment and enhancement neurologists will encounter patients without that the cost of the drug would strain health in relation to psychological and neuro- a diagnosed illness who request medication budgets (Ashworth et al, 2002). However, logical disorders (Outram, 2010). For both to improve their memory, cognitive focus or this did not occur. Ashworth and colleagues Viagra and neuroenhancement, there is attention span. This approach is in line with (2002) conducted an observational study the no relevant life-threatening medical con- arguments that neuroenhancing drugs could year after Viagra was introduced in the UK dition; these drugs are taken to enhance be regulated through prescriptions and and found that it was discussed in only 0.5% lifestyle. Furthermore, a prescription could used under the supervision of health-care of consultations. A prescription was given in be obtained for lifestyle use of these drugs professionals (Greely et al, 2008). 43% of these consultations and doctors gen- by exaggerating or feigning symptoms of An examination of the way in which erally followed the prescribing guidelines. erectile dysfunction for Viagra, or attention Viagra has been managed and regulated Doctors did not feel under pressure to pre- deficit hyperactivity disorder (ADHD) for illustrates some of the potential issues in scribe it, and they generally felt it was jus- neuroenhancing drugs. regulating neuroenhancers through the tifiable to prescribe a lifestyle drug through pharmaceutical regulatory system. Sildenafil the UK National Health Service. However, edia discussions of policy was first approved by the US Food and Drug one-quarter of British doctors believed that responses to enhancement often Administration and equivalent organizations there were no circumstances in which such Mcontrast two extreme positions: in most other nations as a prescription- a prescription was justified. either we should prohibit enhancements only medication. It is now available in the or we should make them freely available. UK as a pharmacy medication that can be Different substances might Advocates of the latter argue that bans on use obtained over the counter under the super- need different types of will not stop the development of enhancers vision of a trained pharmacist. This change or the misuse of existing drugs, and will only was mostly made in response to concerns regulation, as might different make it more difficult to regulate their safety about users who could suffer adverse uses of the same substances and efficacy. Concurrent with this, Greely cardiovascular effects after purchasing the and colleagues have recently suggested that drug over the internet without a prescription An obvious difference between sports the current regulation of psychoactive pre- and without medical supervision (Aronson, doping and Viagra use is that Viagra was scription drugs should be relaxed (Greely 2009). Indeed, the recreational use of Viagra developed as a treatment for a distressing et al, 2008). has been eased by access to it on the inter- condition: erectile dysfunction. The framing However, neither strategy is likely to be net (Smith & Romanelli, 2005; Fox & Ward, of Viagra as a medical treatment allowed it fully effective. The regulation of addictive 2008). This makes it difficult to monitor to be regulated as a pharmaceutical pro drugs shows that prohibition can decrease non-prescribed or off-label use, particularly duct within the medical system. However, their misuse, but rarely completely pre- if drugs are registered for the treatment of there are many types of erectile function vents it. Demand for the drug can create a medical conditions (Schermer et al, 2009). and it might be difficult to decide whether black market, thereby amplifying the prob- a patient has a medical disorder or is within lems caused by illicit use and resulting in The absurdity of students and the normal range. Men who expect to an increased cost to society from enforcing academics submitting urine achieve an erection several times a day and the law. The usual regulatory response to those who expect to achieve one once a recreational drugs is precautionary: to pro- samples is often cited as the logical week obviously have different expectations hibit their use to prevent potentially harm- conclusion of any suggestion that about normal functioning. Santtila and ful consequences, which are often initially neuroenhancement should colleagues (2007) found that recreational unknown. Substances that are eventually be regulated users of Viagra had lower confidence in considered to be less harmful have gener- their ability to achieve an erection than ally been controlled through the regulatory The use of performance-enhancing sub- non-users, even though they had signifi- processes for pharmaceutical products, or stances in sport is prohibited, and the regu- cantly better erectile function. There was an by restricting access, as for nicotine and lation of banned substances is vigorously indication that regular Viagra users became alcohol. Such regulation can limit con- enforced. The initial reason for banning psychologically dependent on it and were sumption and the number of potential users. performance enhancers in sport was con- less confident about their ability to function For pharmaceuticals, regulation also aims cern for the health and well-being of ath- without it. to ensure that safety and efficacy claims letes (Petroczi, 2007), which is the same as The role of expectations is probably are justified. the rationale for banning illicit recreational important for neuroenhancement too; a stu- The way in which drugs are regulated drugs. There is a similar debate about the dent who expects to be top of the class will depends on their specific characteristics. safety of drugs for cognitive enhancement— have different expectations about accept- It is therefore not helpful to discuss neuro particularly in the long term—which pro- able cognitive performance than a student enhancing drugs as a homogeneous cate vides support for the argument that their use who is satisfied with passing the course. gory. Different substances might need should not be allowed.

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