BY ZEHADI ALAM – What if you could take a pill and become smarter? Sound too good to be true? Our epistemic duties would demand skeptical inquiry on our part with respect to such a sensational notion. Claims of such a sort are certainly accompanied by underlying caveats, given that the structure of such an assertion involves a nebulous trait (i.e. smartness) as a variable to be enhanced by a particular mechanism (i.e drug consumption) and is also expressed indiscriminately. Nevertheless, it is possible to start somewhere to meaningfully assess the proposition in question when we take the concept of becoming smarter to mean “enhancing certain cognitive faculties.” These may include factors such as attention, memory, mental endurance, executive function, and learning ability. Drugs that can improve these faculties are known by the name of “nootropics.” The emergence of nootropics in daily life requires those who wish to be familiar on the topic to be informed about several aspects of the ongoing conversation about these compounds, such as the group of people who use them, the different categories of nootropics, the efficacy of these compounds, the studies that address them, the ethical controversy behind using them, and the future potential of these substances.

Nootropics encompass a wide variety of compounds, some of them prescription drugs, others available over-the-counter and online. These drugs have caught the interest of many groups of people who aim to be high-performing in their daily work. Unsurprisingly, this includes college students studying for their courses. According to one study at the University of Kentucky, 30% of its students used ADHD medication for cognitive enhancement. Another U.S. study found that 34% of college students used such drugs for cognitive gains. ADHD medication, especially Adderall, appears to be among the most popular choice of drug for nootropic use, which has raised many concerns surrounding the safety of such usage. Adderall is composed of amphetamine salts, which increase the release of certain neurotransmitters, such as dopamine and norepinephrine. This leads to feelings of increased alertness, focus, and energy. Without a prescription, however, one is likely to consume a non-optimal dose, which raises concerns such as the experience of negative side effects like insomnia and heart palpitations, physical dependence, tolerance, and the possibility of detrimental effects from long-term use, such as depression and headaches. Worries of drug abuse have spilled over to nootropics more broadly.

Nootropics include many different kinds of drugs and compounds. Some of the categories of nootropics are as follows: amino acids, ampakines, carotenoids, choline compounds, eugeroics, herbal supplements, minerals, nucleic acids, omega-3 fatty acids, racetams, and vitamins. This is not an exhaustive list, however excluding ampakines, eugeroics, and racetams, these are typically the sorts of ingredients one will find in a nootropic pill sold by supplement companies. They are made to be taken as one would take a multivitamin, and they allegedly ensure heightened cognitive performance. What role do these ingredients play when it comes to enhancing cognition? Some of these ingredients provide the raw material for the synthesis of certain neurotransmitters like acetylcholine and dopamine, they modulate levels of certain neurotransmitters, exhibit neuroprotective effects, maintain cell membrane integrity, improve neural communication, enhance synaptic growth, increase blood flow to the brain, and increase nerve growth factors (NGF)—just to name a few. Purportedly, these ingredients bring about specific changes that promote overall brain health and improve its function, which leads to better cognitive faculties and a boost in mental performance.

Do these nootropic compounds really provide gains for anyone who takes them? One should critically examine the evidence to inform individual conclusions, as opposed to solely looking at the marketing claims of the companies who sell these supplements. The inferences we can validly make are constrained by the limitations of our generalizations. What does this mean? The performance enhancing properties of many nootropic drugs were found in participants who were not healthy to begin, were of a certain age group, or were non-human animals (i.e. mice). Improvements for these subjects do not necessarily translate to an improvement in healthy humans of any age group. As clinical neurologist Dr. Steven Novella from Yale University School of Medicine points out, a drug that improves the memory of someone with Alzheimer’s disease does not mean that someone without the disease will experience such benefits. One of the categories of nootropics that was previously listed was choline compounds. Alpha GPC and CDP-choline are popular sources of choline in the nootropic community that are taken to increase the brain’s acetylcholine levels, a neurotransmitter that is important for learning and memory—and low in people with Alzheimer’s disease. There are even nootropics that enhance acetylcholine activity by inhibiting the enzyme acetylcholinesterase that breaks down acetylcholine in the brain (e.g. huperzine A and galantamine). All of this sounds good if the brain is in need of more acetylcholine, but if it has enough, additional amounts will not bring about further benefits for memory. As Novella says, “just because a nutrient helps recovery does not mean it will enhance normal function.”

The same point of invalid extrapolation from impaired states to healthy states applies to medication that is prescribed to individuals with narcolepsy and ADHD (e.g. modafinil). Any general article on nootropics as a whole would be remiss to not mention modafinil, the megastar of nootropics. Modafinil has a reputation in the nootropics community as a highly sought after compound due to its powerful fatigue-fighting and executive function enhancing properties. However, Dr. Novella says that modafinil offers a net benefit to individuals with diminished executive function, but not to healthy individuals, due to the way the drug optimizes the way mental resources are utilized. As mentioned, it can also only be legally possessed with a prescription, which leads many to resort to adrafinil, a eugeroic compound that differs from modafinil by the presence of a hydroxyl group on the amine. Adrafinil can be possessed without a prescription, but it is less than ideal because it has to be metabolized into modafinil, the biologically active drug.

Given that these compounds are stimulants, there is a good reason to assume that improved productivity under the use of these drugs is being conflated with cognitive improvement. There is an interesting study that addresses the use of Adderall compared with a placebo. It is conceivable that users can respond by saying that if these drugs can enable them to have greater mental energy and motivation, then that is all the utility they are looking to have. However, the question of cognitive enhancement of the nootropics is still open to further investigation. More high-quality studies involving healthy humans are needed and anticipated. Researchers at the University of Georgia have provided beneficial contributions to the growing need of further nootropic studies.

Although all of the types of compounds thus listed possess nootropic properties, not all of them, such as amino acids, minerals, and vitamins, are marketed as cognitive enhancing substances. Carotenoids are another example; they are pigment compounds that give certain plants their color. Why are carotenoids worthy of attention in the discussion of nootropics? Studies conducted by researchers Dr. Renzi-Hammond and colleagues at the University of Georgia on the carotenoids lutein and zeaxanthin have yielded exciting results that may allow people to confidently take these compounds for nootropic purposes.

Lutein and zeaxanthin are xanthophyll carotenoids found in plants such as kale and spinach. As a supplement, they are marketed for maintaining eye health and vision. These compounds accumulate in the macula of the eye, help filter blue light, and serve as an antioxidant, which offers protection against vision degradation from cataracts and macular degeneration. The utility that they provide in improving brain function adds to their merits. The research of Dr. Renzi-Hammond and colleagues has found that supplementation with lutein and zeaxanthin leads to effects such as neural efficiency, improved white matter integrity, visual processing speed, spatial memory, reasoning ability, and complex attention. Their studies have been conducted on both older adults and younger adults; both age groups experienced cognitive benefits from lutein and zeaxanthin supplementation. Impressively, many of the previously listed effects such as visual processing speed and reasoning ability were found in young, healthy, and well-nourished participants. The results of these studies are very encouraging for current and prospective nootropic users. It is important to mention that benefits from lutein and zeaxanthin were seen over an extended period of time. In the studies referenced, participants were supplemented with lutein and zeaxanthin daily over the span of a year. As more research establishes the effectiveness of certain brain enhancing supplements, the ethical implications regarding their use becomes increasingly relevant.

Would the use of nootropics to boost performance constitute a form of cheating? This is a question that is being considered by universities where the use of smart drugs is becoming more prevalent. Duke University explicitly mentions the use of prescription drugs to improve academic performance as an example of cheating in its section on academic dishonesty on its student conduct page. This makes sense because prescription medication serves a specific purpose to alleviate an impaired biological state and is not legally available to everyone. The legal restriction of access would indeed provide an unfair advantage to those who obtain and use them without a prescription. However, nootropics include many substances that are not prescription-based, and thus students still have the option to use drugs to improve academic performance. There still seems to be a perception that using drugs for such purposes would be wrong, in that it is allegedly analogous to the idea of doping to improve sports performance.

The World Anti-Doping Agency has, in fact, banned the use of certain nootropic compounds, such as modafinil, adrafinil, and phenylpiracetam. Gaining a performance advantage over one’s opponents through the use of certain drugs is a matter that is taken very seriously by sports organizations and is looked down upon by drug detractors due to the notion of having an unfair advantage. This is understandable for sports where the structure of the activity is a competitive one and high performance through effort and training would appear more valuable than bypassing some of the disciplined work with a drug. In competitive sports, there is a separate kind of value that is placed on the process of practice, training, and working hard to prepare for a performance. It is something that speaks to one’s character and inspires a form of respect. As a result, performing better through the use of drugs just seems to be less impressive and praiseworthy to our intuitions.

Does this reasoning apply to academics? There seems to be an important difference. As Stanford Law School professor Henry Greely explains, “[…] sports are entertainment. The world is not better or worse depending on who wins an Olympic gold medal, the Super Bowl, or the World Cup. The world may well be better off if more brains are enhanced, if more people are learning and thinking more effectively.” In academics, one is ultimately striving to be a useful individual who can make positive contributions with their knowledge. Under that perspective, it does not ultimately matter how one comes to be good at solving equations or explaining concepts — just that they are able to do so well because of the instrumental value of such skills. Even if there is value to be found in studying, Greely argues, “the plausible cognitive enhancements would not eliminate the need to study; they would just make studying more effective. In any event, we do not reward effort, we reward success. People with naturally good memories have advantages over others in organic chemistry exams, but they did not work for that good memory.”

Many, if not most students have experienced the frustration of not being able to recall something important during an exam and then remembering it after the exam is over. Exams are often exclusive opportunities for students to demonstrate their knowledge. It is the only evidence most professors will accept in certain courses that a student knows the material. If there is a drug that enhances one’s semantic memory, would it be objectionable for students to take it in order to reduce memory lapses of this sort, which are just moments of bad luck? How about studying and preparing for class? If taking racetams allows one to remember more of what they read in their textbooks, would taking them really be ethically contentious? Where is the line to be drawn regarding which drugs are acceptable to take and which are not? The use of caffeine is acceptable, yet it is very much a drug that can improve one’s performance through its stimulant properties. Many nootropics are also nutritional compounds. Is it wrong to take a cognitive improving compound from a supplement instead of through diet? How about compounds that offer cognitive gains over prolonged periods of time? Is that an important difference to account for when contrasted with drugs that offer effects within an hour? This discussion is far from settled, but these points are left to the reader to contemplate.

The topic of increasing cognitive abilities through drugs will no doubt be a conversation that will continue in the context of many forums. The term “smart drugs” need not only conjure to mind prescription medication for ADHD and narcolepsy, which tends to be the common public perception. As more research is conducted on the efficacy of certain compounds for brain enhancing properties, the advocate and the critic of nootropics will have much to contribute regarding the use of these drugs. Despite criticisms, nootropics can plausibly do more good in a larger perspective. Enhanced attention can prevent an accident, enhanced memory can lead to better decisions, and enhanced learning ability can lead to academic and work success. The allowance of the use of smart drugs under that kind of consideration, far from being forbidden, would seem to be obligatory. As a commentary by researchers in the journal Nature says, “In a world in which human work-spans and lifespans are increasing, cognitive enhancement tools—including the pharmacological—will be increasingly useful for improved quality of life and extended work productivity, as well as to stave off normal and pathological age-related cognitive declines. Safe and effective cognitive enhancers will benefit both the individual and society.”