Pills that keep your mind afloat: What is the downside of brain-enhancing drugs?


Jeremy Laurance
Friday 15 April 2011 00:00 BST

One of life's disappointments is the recognition that we have not realised our potential; the realisation that had we tried harder, worked longer, played less, we might have achieved more. It is the foundation of the mid-life crisis.

Parents say to their children preparing for an exam: "Just do your best." It is supposed to be encouraging – but is it? It is not easy to do your best. Indeed, it may be impossible. This becomes all too clear as we move into adulthood. The fiercest competition of our lives is the one we have with ourselves. There is much more involved than the small matter of will power.

So could we be helped to do our best? The movie Limitless, released recently, deals directly with this conundrum. Its hero, Eddie Morra (Bradley Cooper), is an unkempt, unaccomplished writer who finds a way of bridging the gap between the nobody he is and the somebody he aspires to be – with the drug NZT, rocket fuel for the brain – a cognitive enhancer that turbo-charges memory, cranks up concentration and eliminates fatigue. After swallowing a dose, Eddie completes a hefty chunk of his book in an afternoon, learns the piano in three days, picks up Italian from a Berlitz tape and wins a street fight using moves remembered from Bruce Lee flicks. Women suddenly find him irresistible. So far so good. But NZT has a downside. Soon Eddie is double-dosing, running out of supplies and desperate for more. The movie ends in a confusion of plot twists that has left critics floundering.

The strength of Limitless is the credibility of its central idea. It is not so far- fetched to imagine that "smart drugs" like NZT might one day exist. Versions of them already do – and their use is growing. The key chemical substances in this field are Ritalin, an amphetamine substitute, and its stronger relative Adderall. They are prescribed to children with attention deficit disorder but are increasingly illicitly obtained and used to boost concentration. Provigil, a stimulant prescribed for the sleep disorder, narcolepsy, to increase alertness, is reputedly even better, with greater benefits and fewer side effects. In 2008, a poll of 1,400 scientists from 60 countries conducted by the journal Nature found one in five claimed to have used drugs for cognitive enhancement, slightly more than half taking Ritalin and slightly less than half choosing Provigil. In 2009, a survey of 1,000 students at Cambridge University by Varsity, the student newspaper, found a tenth took prescription drugs to boost brain power.

They may have been encouraged by a 2008 report, from the Academy of Medical Sciences, on the brain, addiction and drugs which suggested a relatively small improvement in memory score of say 10 per cent could lead to a higher A-level grade or class of degree. A small gain in smartness, in other words, can translate into a big gain in outcome.

But do the drugs work? Can they genuinely increase powers of concentration and creative thought? The Independent columnist Johann Hari thought so, after conducting a 10-day experiment with Provigil on himself in 2009. "It was March when I realised my brain was burned out," he wrote. A few clicks of the mouse and a week later he was popping his first pill.

There followed an astonishingly productive few days in which he achieved a prodigious work rate. He found himself able to "glide into deep, effortless, cool" concentration: "It was like I had opened a window in my brain and all the stuffy air had seeped out, to be replaced by a calm breeze."

Hari wondered if it could be the placebo effect – he wasn't sure. He used the drug for five days, stopped for three, when his brain "sagged back to its former depleted state," and then powered up for another five days.

Finally he stopped. "I concluded that taking narcolepsy drugs when you don't have narcolepsy is just stupid."

A study found that Provigil boosted the performance of helicopter pilots flying on simulators who had been deprived of sleep. The US military has taken an interest and in the UK Provigil is being investigated as an aid to maintain surgeons' performance during lengthy, complex operations.

The threat – and the potential – of smart drugs has been debated for 20 years. Others that have been touted as potential candidates include ampakines, a class of stimulants, atomoxetine, a treatment for Parkinson's disease and Donepezil, which slows the progress of Alzheimer's. In each case, however, early enthusiasm has faded as initial positive results have led to later disappointment.

Until Provigil came along there was no real candidate for the role. For a drug to be acceptable to healthy people, it must be virtually free of side effects. Although students facing exams have been happy to take Ritalin and Adderall, they carry risks to the heart and are potentially addictive. Provigil, on the other hand, has few side effects and so far has not demonstrated a potential for abuse.

"Provigil represents the test case for cognitive enhancing drugs," said Barbara Sahakian, professor of clinical neuropsychology at Cambridge.

"As a healthy person you think: 'What are the risks and benefits of this drug?' If the risks are low and there are real benefits, it's tempting." So how real are the benefits? The drugs undoubtedly deliver an energy boost, combating fatigue and improving concentration. But many students take them to compensate for other energy-sapping activities, such as all-night partying, rather than as a chemical aid to boost their grades.

And as one enthusiastic US student user of Adderall put it, it only helps as a cognitive enhancer if you are dedicated to completing the essay you have set out to write: "The number of times I've taken Adderall late at night and decided that, rather than starting my paper, hey, I'll organise my entire music library! I've seen people obsessively cleaning their rooms on it."

The essays he wrote on Adderall also tended to be long-winded, with two pages given to creating an "airtight argument" where a couple of sentences would have sufficed.

There's the rub – the brain is a complex organ and a drug that improves performance in one aspect may hinder it in another. Drugs like Ritalin and Adderall work in part by raising the levels of dopamine in the brain. If you have enough, more may not help – indeed it may leave you over-stimulated and less able to concentrate.

Martha Farah, a psychologist at the University of Pennsylvania, believes the better a person is at a certain task, the less room there is to improve and the less impact the drugs will have on their performance.

"They will help some technically normal people... but those in the lower end of the ability range more than in the higher end," she said.

In other words, smart drugs work best for less smart people. Professor Sahakian rejects this argument. What is "deficient" for a healthy human being? she asks. "We all have times, or periods in our lives, when we could benefit from a cognitive boost.

"Last night I was giving a lecture at 8pm, so I drank coffee because I wanted to be at my best. Then I couldn't sleep because I don't usually take coffee that late. Then I had to come in and do a full day's work next day – and I could have used something to perk me up. People are flying around the world, attending important meetings and they have to be on top form.

"In academia we know people are using [Provigil] to counteract the effects of jetlag, to enhance productivity or to deal with intellectual challenges. Young mothers and shift workers struggle to maintain their mental alertness. We are all having to work longer and retire later. When we are older, even if we are healthy, we are not the same as we were in our 20s – cognitive performance declines with age. Cognitive enhancers with small or no side effects but with moderate enhancing effects that alleviate forgetfulness or enable one to focus on the task at hand would be unlikely to meet much objection," she said.

In 2009, Sahakian was co-opted on to a committee, set up by the UK Advisory Council on the Misuse of Drugs, to look at the use of cognitive enhancing drugs by healthy people. But the committee lapsed when the council was riven by a dispute with the government over the classification of cannabis and its chairman, Professor David Nutt and several members resigned. It has yet to be reconstituted. While few would consider a double shot of espresso as conferring an unfair advantage at work, the ethics of using smart drugs are hotly debated. Two years ago Vince Cakic, a psychologist at the University of Sydney, warned that academic "doping" was becoming as routine as in sport and foresaw the time when students might have to submit to urine tests. But Cakic acknowledged banning drugs because of their unfair advantage made little sense when richer students could pay for private tuition.

Anjan Chatterjee, a neurologist at the University of Pennsylvania, has drawn a parallel with cosmetic surgery used by the rich to refine what nature gave them.

"Cosmetic neurology", he suggests, offers a different kind of personal improvement – the "nip and tuck" for the mind.

Yet the boundary between therapy and enhancement can be hard to define. Short people can be treated with growth hormone – but is that cosmetic or therapeutic? In an ageing society, treatments to boost attention, learning and memory will be increasingly relevant – but should they be applied to people who are healthy but merely old? The image of Eddie Morra, a young not very accomplished writer popping pills to help him complete his first book, may make many people as queasy as the idea of students swallowing handfuls of Ritalin to get them through their exams. When we are forced to rely on chemical enhancement to improve our performance in a competitive world, we are being pushed too far.

On the other hand there are situations where it is easy to see such drugs may have a valuable, even life-saving, role – by air-traffic controllers, soldiers in combat and surgeons facing long hours at the operating table.

Professor Sahakian is working with Lord Ara Darzi, the surgeon and former Labour health minister, who, she says, is concerned about the amount of coffee some surgeons drink to keep them alert. Caffeine in coffee causes a tremor of the hands when taken in quantity, not an asset to be welcomed in a surgeon. A clear need there, then, for a smarter drug.

The Oxford Handbook of Neuroethics, edited by Barbara Sahakian and Judy Illes. Oxford University Press

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