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Central nervous system stimulants

The genius is out of the bottle: smart drugs are here to stay

More research is needed into the long-term effects of modafinil and, if proven safe, it deserves the same level of acceptance as caffeine.

More research is needed into the long-term effects of modafinil and, if proven safe, it deserves the same level of acceptance as caffeine

Source: istockphoto.com

All over the world, people drown their fatigue in cups of tea or coffee, or in the nectar of carbonated wakefulness in the form of Red Bull or other energy drinks.

Caffeine is the acceptable face of cognitive enhancement. However, newer and potentially more beneficial cognitive enhancers, such as modafinil, have emerged. If proven effective and safe, these so-called “smart drugs” deserve the same level of acceptance in society.

Cognitive enhancers

Modafinil and other popular smart drugs, such as methylphenidate (e.g. Ritalin), were originally developed to treat neuropsychiatric conditions such as narcolepsy, Alzheimer’s disease and attention deficit-hyperactivity disorder[1]. The logic is simple: if these pharmacological agents can help distracted, sleepy, forgetful people function normally, then they can give healthy people a boost in terms of focus, wakefulness and memory; all attributes that could potentially enhance academic or on-the-job performance.

Research into the effects of cognitive neuroenhancers on healthy individuals has increased over the past three decades. Entering the terms “modafinil” and “cognitive” into MEDLINE, the leading online repository for medical research, returns around 270 hits[2]. Among these hits are 24 relevant studies that focus specifically on the effects of modafinil in healthy humans. The studies in question are also relatively methodologically robust. For example, they all employ a control group or condition and randomly select participants to receive either modafinil or a placebo. It is these 24 studies that recently became the basis for a review of modafinil’s cognitive-enhancing effects in healthy adults. The review[2], undertaken by researchers from the University of Oxford and Harvard University, set out to answer two basic questions: one, looking across all the relevant studies, does modafinil have cognitive-neuroenhancing effects on healthy adults; and two, is it safe? The short answer turned out to be “yes” and “yes”.

The rise of modafinil

Modafinil was first developed and marketed in France as a treatment for narcolepsy. Subsequently, it also received US Food and Drug Administration approval for the treatment of obstructive sleep apnoea and shift work sleep disorder[3]. Sold globally under various brand names such as Provigil, Modavigil and Modiodal, modafinil has become more well known for its extensive off-label use as a smart drug[1]. The Oxford-Harvard review empirically confirmed what the pill-popping students and professors have long suspected: modafinil beneficially enhances cognition. Although the results of the review were far from black and white, the authors concluded that “modafinil exerts a complex effect on cognitive domains, in general driving benefits in attention and memory through enhancement of higher executive functions”[2]. Furthermore, modafinil appeared to be particularly beneficial when participants were asked to complete more complex cognitive tasks.

The vast majority (78%) of studies reported that there were no safety issues. When side effects were reported, they tended to be limited to a small number of participants and included symptoms such as insomnia, headache, stomach ache and dry mouth. In short, as in previous studies, modafinil was associated with low risk of abuse and limited side effects, all of which were well tolerated and reversible[2],[4]. Modafinil, at least in the short term, appears to be safe.

This review opens up the question of modafinil’s legitimate, society-wide use as a cognitive neuroenhancer, be that in the form of a smart pill, or even as the active agent in a hypothetical new “study drink”. Modafinil is already widely used or misused (depending on your position) on university campuses. A recent survey by a team at King’s College London reported that 9.4% of 877 students surveyed had used either modafinil, Adderall (amfetamine and dextroamfetamine) or Ritalin (methylphenidate) at least once[5]. While 9.4% is a far cry from media reports suggesting smart drug use is “rife” in British universities[6], there is undoubtedly an ethical issue emerging.

Is it cheating?

At the Seoul Olympics in 1988, 100m sprinter Ben Johnson was unceremoniously stripped of his gold medal and world record. His crime? He tested positive for the performance-enhancing anabolic steroid, stanozolol. Should today’s student scoring high in her exam and subsequently testing positive for a known cognitive enhancer be similarly stripped of her accolade?

At the inquiry sparked by the Ben Johnson doping scandal, Johnson’s coach argued that doping was widespread within athletics, and that Johnson had to use steroids to remain on equal terms with the other top athletes known to be benefiting from such performance-enhancing substances.

So what is the hardworking student to do when she perceives herself being displaced from the top of the class by students known to use cognitive enhancers? Does she gracefully fade to mid-class mediocrity, and jeopardise her chance of getting into a top medical school, or does she do the same as Johnson (or more recently Lance Armstrong) and join the party?

Consider also students or employees who hate the idea of cognitive neuroenhancement. Might their concerned parent or employer excerpt subtle, and if necessary not so subtle, pressure to encourage the consumption of such performance-enhancing agents? A debate is required on the legitimate use of cognitive enhancers, an iterative debate fed by scientific research and further debate. If cognitive enhancers are to be used – and they are being used at the moment – then there must be guidelines and consumer protection in place.

Competitive edge

Increasingly a nation’s economic success and competitive advantage are based on the effective use of knowledge. The term “knowledge economy” has been widely used to describe this idea. An essential pillar of the knowledge economy is, of course, education. The most knowledgeable and innovative nations will thrive in the emerging knowledge economy, and the pressure is on to do well. One could argue that any nation unilaterally banning cognitive neuroenhancment would be hamstringing itself in this race. Its students would not perform as well as those from other nations.

Furthermore, nowadays the idea of life-long learning has become a reality. The information age has enabled us to have access to the latest evidence and information even once we graduate and leave the hallowed halls of academia. If you had a hard-to-diagnose and potentially life-threatening health condition, all else being equal, which physician would you want working your case: the one on modafinil or his slightly sleepy looking counterpart?

Historic parallel

Our current rather ambivalent relationship towards smart drugs has a historical parallel. In Islamic law, for many centuries there were heated debates about the status of coffee (qahwa). For example, in 1511, the governor of Mecca, Khair-Beg, likened coffee to wine and outlawed its consumption. He also went on to close all of Mecca’s coffeehouses. This hugely unpopular prohibition was short-lived, and the Sultan, himself a habitual coffee drinker, quickly reversed Khiar-Beg’s edict. Central to the arguments that ultimately kept coffee off Islam’s prohibited substance list was the drink’s perceived positive effects on cognition, and its ability to help students better study the sacred sciences[7].

There is no doubt that more research is needed (and welcome) to examine the long-term effects of agents such as modafinil. And, if the long-term effects are beneficial, then there is no reason to stop people using these cognitive enhancers responsibly, in the same way as drinking a cup of coffee.

Justin Thomas is associate professor at the College of Sustainability Sciences and Humanities, Zayed University, Abu Dhabi. 

Citation: The Pharmaceutical Journal DOI: 10.1211/PJ.2015.20069302

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