By Marek Kohn
Are we asking the right questions about pills designed to boost brainpower?
Marek Kohn looks at what they can do for us and what they can t.
You know how they say that we can only access 20% of our brain? says the man
who offers stressed-out writer Eddie Morra a fateful pill in the 2011 film
Limitless. Well, what this does, it lets you access all of it. Morra is
instantly transformed into a superhuman by the fictitious drug NZT-48. Granted
access to all cognitive areas, he learns to play the piano in three days,
finishes writing his book in four, and swiftly makes himself a millionaire.
Limitless is what you get when you flatter yourself that your head houses the
most complex known object in the universe, and you run away with the notion
that it must have powers to match.
A number of so-called smart drugs or cognitive enhancers have captured
attention recently, from stimulants such as modafinil, to amphetamines (often
prescribed under the name Adderall) and methylphenidate (also known by its
brand name Ritalin). According to widespread news reports, students have begun
using these drugs to enhance their performance in school and college, and are
continuing to do so in their professional lives.
Yet are these smart drugs all they are cracked up to be? Can they really make
all of us more intelligent or learn more? Should we be asking deeper questions
about what these pharmaceuticals can and can t do?
Thought process
Cognition is a suite of mental phenomena that includes memory, attention and
executive functions, and any drug would have to enhance executive functions to
be considered truly smart . Executive functions occupy the higher levels of
thought: reasoning, planning, directing attention to information that is
relevant (and away from stimuli that aren t), and thinking about what to do
rather than acting on impulse or instinct. You activate executive functions
when you tell yourself to count to 10 instead of saying something you may
regret. They are what we use to make our actions moral and what we think of
when we think about what makes us human.
Smart drugs may enhance focus, but they don't make you smarter (Thinkstock)
These are quite abstract concepts, though. There is a large gap, a grey area in
between these concepts and our knowledge of how the brain functions
physiologically and it s in this grey area that cognitive enhancer
development has to operate. Amy Arnsten, Professor of Neurobiology at Yale
Medical School, is investigating how the cells in the brain work together to
produce our higher cognition and executive function, which she describes as
being able to think about things that aren t currently stimulating your senses,
the fundamentals of abstraction. This involves mental representations of our
goals for the future, even if it s the future in just a few seconds.
The prefrontal cortex at the front of the brain is the zone that produces such
representations, and it is the focus of Arnsten s work. The way the prefrontal
cortex creates these representations is by having pyramidal cells they re
actually shaped like little pyramids exciting each other. They keep each
other firing, even when there s no information coming in from the environment
to stimulate the circuits, she explains.
Several chemical influences can completely disconnect those circuits so they re
no longer able to excite each other. That s what happens when we re tired,
when we re stressed. Drugs like caffeine and nicotine enhance the
neurotransmitter acetylcholine, which helps restore function to the circuits.
Hence people drink tea and coffee, or smoke cigarettes, to try and put [the]
prefrontal cortex into a more optimal state .
True enhancement
In a broad sense, this is enhancement; in a stricter one, it s optimisation. I
think people think about smart drugs the way they think about steroids in
athletics, Arnsten says, but it s not a proper analogy, because with steroids
you re creating more muscle. With smart drugs, all you re doing is taking the
brain that you have and putting it in its optimal chemical state. You re not
taking Homer Simpson and making him into Einstein.
Smart drugs have provoked anxiety about whether students who take drugs to
enhance performance are cheating, and whether they will put pressure on their
peers to do likewise to avoid being at a competitive disadvantage.
Some students who use smart drugs say it makes studying more pleasurable
(Thinkstock)
Yet some researchers point out these drugs may not be enhancing cognition
directly, but simply improving the user s state of mind making work more
pleasurable and enhancing focus. I m just not seeing the evidence that
indicates these are clear cognition enhancers, says Martin Sarter, a professor
at the University of Michigan, who thinks they may be achieving their effects
by relieving tiredness and boredom. What most of these are actually doing is
enabling the person who s taking them to focus, says Steven Rose, emeritus
professor of life sciences at the Open University. It s peripheral to the
learning process itself.
Or as one US student told researcher Scott Vrecko in 2013: I remember getting
just completely absorbed in one book, and then another, and as I was writing I
was making connections between them [and] actually enjoying the process of
putting ideas together. I hadn t had that before.
Dangerous substances?
That doesn t necessarily mean all smart drugs now and in the future will be
harmless, however. The brain is complicated. In trying to upgrade it, you risk
upsetting its intricate balance. It s not just about more, it s about having
to be exquisitely and exactly right. And that s very hard to do, says
Arnstein. What s good for one system may be bad for another system, adds
Trevor Robbins, Professor of Cognitive Neuroscience at the University of
Cambridge. It s clear from the experimental literature that you can affect
memory with pharmacological agents, but the problem is keeping them safe.
Drugs and catastrophe are seemingly never far apart, whether in laboratories,
real life or Limitless. Downsides are all but unavoidable: if a drug enhances
one particular cognitive function, the price may be paid by other functions. To
enhance one dimension of cognition, you ll need to appropriate resources that
would otherwise be available for others.
There are costs to narrowing your attention, Sarter points out. Not only all
the stuff in the periphery that might be very significant that you might be
missing, but internally if you narrow your attentional field, it also narrows
the range and scope of associations you could bring into your thought process.
In many settings that could well prove costly. But in others, where you re not
being asked to think about the meaning of life, it could be beneficial, such as
an air traffic controller, for example.
The brain is complex, so enhancing one talent with drugs may hamper others
(Thinkstock)
If paying Paul always requires robbing Peter, we can t expect drugs to produce
a general, cortex-wide expansion of cognition. But by allocating extra
resources to one domain or the other, could you surpass the maximum levels you
could previously have attained or even the highest levels attained by anyone?
I think you can and you will, says Sarter, but crucially, only for very
specific tasks. For example, one of cognitive psychology s most famous findings
is that people can typically hold seven items of information in their working
memory. Could a drug push the figure up to nine or 10? Yes. If you re asked to
do nothing else, why not? That s a fairly simple function.
Future enhancement
So is there a future in smart drugs? Some scientists are more optimistic than
others. Gary Lynch, a professor in the School of Medicine at the University of
California, Irvine argues that recent advances in neuroscience have opened the
way for the smart design of drugs, configured for specific biological targets
in the brain. Memory enhancement is not very far off, he says, although the
prospects for other kinds of mental enhancement are very difficult to know To
me, there s an inevitability to the thing, but a timeline is difficult.
In the nearer future, Lynch points to nicotinic receptor agents molecules
that act on the neurotransmitter receptors affected by nicotine as ones to
watch when looking out for potential new cognitive enhancers. Sarter agrees: a
class of agents known as α4β2* nicotinic receptor agonists, he says, seem to
act on mechanisms that control attention. Among the currently known candidates,
he believes they come closest to fulfilling the criteria for true cognition
enhancers.
Some pharmaceutical companies have decided not to invest in smart drugs
(Thinkstock)
Sarter is downbeat, however, about the likelihood of the pharmaceutical
industry actually turning candidate smart drugs into products. Its interest in
cognitive enhancers is shrinking, he says, because these drugs are not working
for the big indications, which is the market that drives these developments.
Even adult ADHD has not been considered a sufficiently attractive large market.
A substance called piracetam was once widely touted as a smart drug, as Rose
recalled in a commentary piece published in 2002. Piracetam still has its
enthusiasts, but its name is now mostly a reminder that candidate drugs come
and go. There have been a lot of clinical trials for a lot of substances that
didn t do anything, observes Sarter.
Frustrated by the lack of results, pharmaceutical companies have been shutting
down their psychiatric drug research programmes. Traditional methods, such as
synthesising new molecules and seeing what effect they have on symptoms, seem
to have run their course. A shift of strategy is looming, towards research that
focuses on genes and brain circuitry rather than chemicals. The shift will
prolong the wait for new blockbuster drugs further, as the new systems are
developed, and offers no guarantees of results.
Open questions
In the meantime, there are unanswered questions about the suite of drugs people
already take in the hope of enhancing their cognitive powers questions about
whether they work, how they work, the effects they have on the mind after their
initial novelty has worn off, and the effects they may have on our health and
wellbeing in the long term.
Would you take drugs if they enhanced your memory, for example? (Thinkstock)
Despite decades of study, a full picture has yet to emerge of the cognitive
effects of the classic psychostimulants and modafinil. Part of the problem is
that getting rats, or indeed students, to do puzzles in laboratories may not be
a reliable guide to the drugs effects in the wider world. Drugs have
complicated effects on individuals living complicated lives. Determining that
methylphenidate enhances cognition in rats by acting on their prefrontal cortex
doesn t tell you the potential impact that its effects on mood or motivation
may have on human cognition.
It may also be necessary to ask not just whether a drug enhances cognition, but
in whom. Researchers at the University of Sussex have found that nicotine
improved performance on memory tests in young adults who carried one variant of
a particular gene but not in those with a different version. In addition, there
are already hints that the smarter you are, the less smart drugs will do for
you. One study found that modafinil improved performance in a group of students
whose mean IQ was 106, but not in a group with an average of 115.
Perhaps it s time, then, that we start asking much smarter questions about
smart drugs.