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Nootropics – 2020 SCIENCE2020 SCIENCE

Excerpted from a early draft of The Moviegoer’s Guide to the Future; inspired by the movie Limitless. 

In 2004, the academic and medical doctor Anjan Chatterjee wrote a review of what he termed “Cosmetic Neurology”.[1] He was far from the first person to write about the emergence and ethics of cognitive enhancers, but the piece caught my attention because of the unusualness of its title.

Chatterjee’s title has its roots in cosmetic surgery, an area fraught with medical angst as surgeons weigh up the pros and cons of desirable but physiologically unnecessary surgical interventions. Through the article, Chatterjee grapples with similar challenges as he weighs up the benefits and downsides of treatments that don’t cure disease, but extend abilities.

I’m not sure the term “cosmetic neurology” works. “Cosmetic” has an air of frivolity about it that is far removed from the issues Chatterjee is grapping with here. These include the use of substances to compensate for perceived deficiencies in human performance, such as the ability of pilots to remain alert and perform at their best. In the article, Chatterjee explores a growing number of pharmaceuticals that are known to affect the brain’s operations in ways that can improve aspects of performance, including memory and concentration. And while he struggles with the ethics of cognitive enhancers, he wonders whether a “better brain” may, one day, be seen as an inalienable right.

It could be argued of course that this has already happened in a country that’s caffeine-fueled by Starbucks, Dunkin’ Donut, Tim Hortons, and numerous other retail chains offering over-the-counter mental stimulants. For as long as people have known that some substances affect the brain, they’ve been finding ways to make use of these effects; and caffeine is an obvious poster-child here. Take the twentieth century French writer Honoré de Balzac for instance. He was well-known for a prolific coffee habit, writing with rather obvious self-awareness that, after drinking the substance,

“[t]he cavalry of metaphor deploys with a magnificent gallop; the artillery of logic rushes up with clattering wagons and cartridges; on imagination’s order, sharpshooters sight and fire…”.[2]

In fact, reading his work, it’s hard to avoid wondering just how caffiene’d up he was!

Although caffeine in the form of tea and coffee is deeply socialized these days, there’s a growing market for high-dosage shots to keep the brain alert. Visiting our campus one-stop store, there’s a whole array of caffeine-enriched energy drinks and shots that students (and presumably faculty) can use to keep their brains alert. But these are just the visible tip of smart drugs being used on campuses the world over.

For a number of years now, students in particular have been using substances like Adderall, Ritalin and Modafinil to give their brains a boost. These are all regulated substances that are designed for purposes other than getting through college, or finishing the latest class assignment. But this isn’t stopping what is purportedly a thriving black market in pharmaceutical smart pills.

Adderall is intended for use in treating conditions like attention deficit hyperactivity disorder (ADHD) and narcolepsy. But there’s a perception that it also increases memory performance and concentration in healthy adults.[3] Ritalin (or methylphenidate) is another drug used to treat ADHD that is also used off-label for memory and concentration boosts. Modafinil (or Provigil) on the other hand is aimed specifically at treating sleep disorders, and is used off-label to increase wakefulness and counter fatigue by otherwise healthy adults. It’s also used by the military in a number of countries to keep soldiers alert, and has even reportedly been used by astronauts to stave off fatigue.[4]

These and other prescription drugs show measurable effects on concentration and wakefulness in some studies. But their precise impact on performance often depends on who uses them, how they use them, and what they use them for. And in most cases, there are tradeoffs. These may take the form of unwanted short-term side effects and inadequate performance boosts. And in some instances, there may actually be long-term impacts on cognitive performance; although the research here is patchy. Yet despite this, there’s been a steady stream of news articles over the past few years indicating frequent use amongst students and professionals in jobs where being smart matters.

That said, it’s surprisingly tough to get a hard fix on how prevalent this behavior is. A number of studies suggest that up to 50% of students in different countries are using some form of artificial means to increase concentration and performance, but these include caffeine-based drinks and tobacco. The numbers using off-label drugs like Modafinil are just a few percent in many of these studies. Despite the published data though, it’s not uncommon to come across occasional use amongst students. A few years ago for instance, I was discussing smart drugs as part of a project with a group of colleagues. At one point, we turned to our student research assistant and asked whether her peers really were using these substances. She sheepishly reached into her bag and bought out a small pill, “just for when I need it” she said.

It’s not just students though. I regularly come across rumors of faculty members and researchers occasionally using artificial aids to finish a grant proposal or to put an academic publication to bed. In 2008, Barbara Sahakian and Sharon Morein-Zamir published the delightfully-titled commentary “Professor’s little helper” in the journal Nature.[5] In their piece they noted that

“In academia, we know that a number of our scientific colleagues in the United States and the United Kingdom already use mondafinil to counteract the effects of jetlag, to enhance productivity or mental energy, or to deal with demanding and important intellectual challenges.”

The article prompted Nature to conduct a straw poll of the journal’s readers. One in five of the survey’s respondents admitted to using Ritalin, Modafinil, or beta-blockers, to aid their focus, concentration or memory.[6]

Of course, the downside of this academic brain-hacking is that none of these substances are risk-free. Making the decision to use one of these prescription “Professor’s little helpers” to get ahead of your peers requires some careful balancing of short term gains against potential downsides. These could include headaches, diarrhea, agitation, sleeplessness, odd behavior,[7] hair loss, and the need for increasing doses to get the same effect.

Because the side effects of off-label prescription drugs use aren’t widely tracked, it’s hard to tell just how safe or otherwise their use is, although the indications are that moderate or occasional use aren’t likely to lead to serious or lasting problems. But this uncertainty has led to experimentation around less restricted — and often less studied — substances in the quest for the perfect cognitive enhancer: the one that boosts your brain’s abilities without any unwanted downsides.

***

In 1973, the Romanian researcher and M.D. Cornelius Giurgea published an article on a new drug called Piracetam.[8] What was unusual about Piracetam was its seeming inertness compared to other pharmaceutical drugs. According to Giurgea, even at high doses, it showed “no sedation or tranquilization, no stimulation, no interference with synaptical transmitters, no acute or long-term toxicity … no cortical or subcortical EEG changes, no interference with limbic after-discharges, reticular sensori or direct arousal threshold” and “no changes of the cardiovascular, respiratory, gastrointestinal systems”. In other words, it did pretty much nothing. Except that, based on Giurgea’s research, it protected against severe brain hypoxia (oxygen deprivation); and it enhanced learning and memory.

To Giurgea, Piracetam was a unique class of drug that enhanced the integration of evolutionarily important brain functions like memory and learning, without obviously deleterious side effects. He considered this class of drug so unique that he coined a new term for it from the root “noos” referring to “mind”, and “tropein” meaning “towards”. And so “nootropics” were born.

Since then, the term nootropics has been used to cover pretty much all types of substances that purportedly enhance brain function. But increasingly, purists are going back to Giurgea’s roots, and using it to describe cocktails and “stacks” that improve function without unwanted side effects. And to them, this means discounting those off-label prescription drugs.

Piracetam remains a popular nootropic, and is readily purchased in many countries (although it occupies a legal gray zone in some); and there’s a growing body of research on its use and effects. A quick search on Google Scholar pulls up over 19,000 papers and articles on the substance. That said, the benefits to healthy adults remain ambiguous. But this doesn’t stop people using it to, in the words of one supplier “give you a serious cognitive edge without putting your health at risk”.

This is just the tip of the cognitive enhancement iceberg though. Increasingly, advocates like George Burke and others are experimenting with increasingly esoteric cocktails of substances to boost their brains, and to tap into what they believe is their full potential. And it’s not hard to see why. If your livelihood and ambitions depend on your ability to squeeze every last ounce of performance out of your brain, why wouldn’t you try everything possible to make sure you were running at peak performance?

This, of course, assumes that most people aren’t running on all four cylinders in the smarts department in the first place, and that our brains have the capacity to work better than they do. In Limitless, the plot depends on the old myth that we’re only using 10% – 20% of our brains, and that chemical enhancement can unlock the rest of our presumably unused potential. Sadly, while this works as a plot device, it’s pure scientific bunkum.[9]

Admittedly, there’s still a whole lot of stuff we don’t know about our brains. But we do know that evolution abhors waste. Even if we don’t understand the intricacies of the inner workings of what’s in our heads, it’s a pretty fair bet that everything in there does something that’s useful. This can be shown in part from brain imaging, and functional Magnetic Resonance Imaging in particular. But even here, if we don’t know what to expect from our neurons and synapses in the first place, we can hardly claim they’re not doing their job.

What’s more interesting to me is the idea that’s developed in Limitless that we could chemically enhance memory storage and recall, and the ability to make sense of the seemingly disparate pieces of information we all have tucked away in our heads. Certainly, I struggle with memory and recall; and my ability to make sense of and act on new information suffers as a result. It’s easy for me to fantasize about how much smarter I’d be if everything I’ve experienced or learned was always at my fingertips, just waiting to be combined together in a flash of genius. And while I may be using 100% of my brain, it doesn’t take much to convince me that 90% of this is a dysfunctional mess.

To someone who depends on their brain for their living, I must confess that the idea of clearing the fog and making things work better is attractive. Surely with better recall and data processing I’d be better at what I do. And maybe I would. But there’s a danger to thinking of our brains as computers; which of course is where these ideas of memory and data processing come from. It’s tempting to confuse what’s important in our heads to what we think is important in our computers, including more memory, faster recall, and more efficient data processing. And if we follow this pathway, we run the risk of sacrificing what may be essential parts of ourselves for what we misunderstandingly think is important.

Unfortunately, we don’t know enough about the human brain yet to understand the benefits and dangers of how we think about human intelligence and success, although we do know that comparing what’s in our head to a computer is probably a bad idea.[10] More than this though, we also have a tendency to conflate achievements that we associated with intelligence, to success. But what if we’re using the wrong measures of success here? What if our urge to take more money, to publish more papers, or to be famous, leads to us ultimately risking what makes us who we are? And does this even matter?

To many people, I suspect it doesn’t. And this leads us into the ethics of smart drugs; irrespective of what they can or cannot do for us.

_____

The Moviegoer’s Guide to the Future will be published Early 2019 by Mango Press

[1] Chaterjee, A. (2004). “Cosmetic neurology. The controversy over enhancing movement, mentation, and mood.” Neurology 63: 968–974.

[2] Taken from The World of Caffeine: The Science and Culture of the World’s Most Popular Drug, by Bennett Alan Weinberg and Bonnie K. Bealer. (Routledge, 2002) Balzac had a stupendous coffee habit, and ended up eating the grounds to achieve the enlightenment he craved. He dies at 49, not necessarily from hacking his brain with the brown stuff.

[3] There’s surprisingly little evidence that Adderall does increase performance in healthy adults. There’s more evidence to suggest it can enhance how well you think you’re performing. Sadly, university professors rarely grade on how well you think you’ve done!

[4] See Maxwell J. Mehlman (2004) Cognition-Enhancing Drugs. The Millibank Quarterly, volume 83 issue 3, pages 483 – 506 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2690227/

[5] Nature 450(7173):1157-9 · January 2008

[6] Nature, April 9 2008. Poll results: look who’s doping http://www.nature.com/news/2008/080409/full/452674a.html Accessed February 17 2018

[7] Admittedly, this one may be difficult to detect in academics.

[8] Giurgea, C. (1973). “The “Nootropic” Approach to the Pharmacology of the Integrative Activity of the Brain.” Conditional Reflex 8(2): 108-115. https://nootroo.com/researchvault/the-nootropic-approach-to-the-pharmacology-of-the-integrative-activity-of-the-brain-1973/

[9] This 2008 article in Scientific American is pretty good at debunking the 10% myth: Do People Only Use 10 Percent of Their Brains? https://www.scientificamerican.com/article/do-people-only-use-10-percent-of-their-brains/

[10] It’s amazing how readily we compare the human brain to the latest form of digital technology. Yet the reality its that our brains are nothing like the chips in our smartphones or laptops, or even the processors at the heart of supercomputers.

Photo by pina messina on Unsplash

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