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Think positive: the rise of 'smart drugs'

More and more people are turning to nootropics or 'smart drugs' to enhance their cognitive ability. But what do they do, what are the risks and where do the ethical boundaries lie?

Think positive 

Imagine popping a pill, and suddenly being able to operate at a higher level of cognitive function, outstripping your peers in academia or the workplace and riding a fast track to success. It may sound too good to be true, but it seems a startling number of people around the world are taking drugs in the hope of achieving just that result.

There is a wealth of data showing that certain drug classes can improve cognitive function in dementia and other mental disorders, and it is an inevitable consequence of this research that some groups have started to look at whether drugs can provide a boost to the mental faculties of healthy people as well.

Brain boost
The concept is well established in popular culture, with notable examples including the Snap performance enhancer found in Iain Banks' Culture series of science fiction books and NZT-48, a drug which transforms Bradley Cooper's feckless writer Eddie Morra into a mental superhuman in 2011 movie Limitless.

What is less well known perhaps is how widespread use of supposedly brain-boosting drugs is right now. So-called 'smart drugs' - also known as cognition enhancers or nootropics - seem to be finding their way into the hands of the public in increasing quantities, at least in academic circles.

In 2008, an informal survey by the journal Nature found that around 20 per cent of its readers had used drugs to boost their brainpower, mainly for improving concentration. The most common drugs used by the respondents were stimulants such as attention-deficit hyperactivity disorder (ADHD) treatment methamphetamine and modafinil, the active ingredient in Cephalon's narcolepsy treatment Provigil and its generic copies.

More recently, a German study looking at psychoactive drugs in university students, found that around 7 per cent had used neuro-enhancing drugs, mainly for improving concentration and vigilance.

Outside academic circles the picture is somewhat different. A recently published report by the Wellcome Trust derived from a survey of 1,400 adults and 460 young people suggests that while use of smart drugs among the general population remains pretty rare, attitudes are fairly tolerant. 

Just 2 per cent of adults and 1 per cent of young people said they had used cognitive enhancers in the past, but around half thought medications normally used to treat conditions like ADHD and Alzheimer's disease are an effective means of improving focus, memory or concentration in healthy people, and 31 per cent said they felt it was acceptable to take them.

Add a sprinkling of media hyperbole - a Google news search reveals dozens of articles in the last few months alone for example - and the stage looks set for smart drugs to move increasingly into mainstream use.

Smart drugs are finding their way into the hands of the public in increasing quantities

Looking at the evidence
But how robust is the evidence for their benefits? Mitul Mehta of King's College London in the UK, a specialist in cognitive psychopharmacology, says there are some suggestions from controlled studies that short-term memory can be improved by smart drugs, and a larger body of evidence that they can help people improve focus on a task.

“The evidence they can improve attention is quite clear, while the evidence they can enhance memory is mixed,” according to Mehta.

With that in mind, it is perhaps telling that older drugs that were almost synonymous with cognitive enhancement a few years ago - namely cholinesterase inhibitors, such as donepezil and rivastigmine and the glutamate antagonist memantine - no longer seem to be in vogue.

One reason could be that their benefits on cognition are simply too modest, but it is also possible these drugs are less used because they do not cause positive mood changes, which are reported with both methylphenidate and modafinil, says Mehta, who freely admits this hypothesis is untested.

“There are studies now which show that while stimulants and modafinil have fairly weak effects on cognitive performance, they have clear effects on confidence. That might convince you that you are performing better whilst on a drug even if you are not,” he notes.

Assuming smart drugs are found, which are both effective and safe, should they be widely used?

Beyond the comfort zone
A major impediment to research in this area is lack of funding for trials that could answer once and for all whether some of these drugs do actually have an impact on performance. For the pharma industry, developing a drug to improve a healthy person is beyond its comfort zone (consider how hard it has been to get new drugs approved for obesity), and outside the established framework of regulatory approval, medical insurance and reimbursement for new medicines.

There are, however, a couple of academia-sponsored studies ongoing, including a placebo-controlled 48-person trial of an n-methyl-d-aspartate (NMDA) receptor partial agonist called GLYX-13, which will look at the effect of a single dose of the drug on learning and memory. The trial - sponsored by Northwestern University in the US - was scheduled to get underway this month and should conclude in 2014. The drug is licensed to pharma company Naurex, which is focusing primarily on developing GLYX-13 as a rapid-acting antidepressant that exerts its effects within hours rather than weeks.

Is it safe?
At the risk of spoilers, Eddie in Limitless soon discovers that there is a serious downside to his neurological performance addiction, and away from the drama of Hollywood there are concerns about the long-term effects of the current crop of cognitive enhancers.

In particular, use of stimulants raises the risk of addiction and cardiovascular effects, and some amphetamine-like compounds used as smart drugs are linked to the development of paranoia and even full-blown psychosis. Modafinil meanwhile has also been linked to psychiatric symptoms, hypersensitivity reactions and severe rashes.

That said, in a recent debate organised by the journal Neuropharmacology, David Nutt, director of the neuropsychopharmacology unit at Imperial College London in the UK, noted that there is very little evidence that people who use stimulants in this way go on to require treatment for dependency. And with decades of experience with methylphenidate and modafinil there does not seem to be any major health issues surrounding their use.

Arguably even more worrying is the reality that these drugs are not going to be sourced from legitimate supply channels in the vast majority of cases. Many will be sourced over the Internet, for example, where the risks of buying counterfeit, substandard and adulterated medicines are well established.

Barbara Sahakian, a professor of neuroscience at Cambridge University, covered the use of cognitive enhancers during a discussion at the Hay Festival in Wales recently, warning that Internet-sourced smart drugs place users at risk of ingesting products that are likely of no benefit and at worst a danger to health.

Moreover, she pointed out that use of methylphenidate by students has been shown to cause sleep disruption in some cases, which actually reduces the capacity to retain information.

Is it right?
There are also clearly ethical considerations. Assuming smart drugs are found, which are both effective and safe, should they be used widely, for example to boost productivity in the workplace and make businesses more competitive, or just be limited to individuals with a clinical cognitive dysfunction? One could argue for example that some critical professions such as surgeons and airline pilots should take them to reduce the risk of mishap.

Sahakian recently gave the following example to illustrate this dilemma. “Imagine two surgeons, one who has been drinking coffee to stay alert and has hand tremors and the other who has been taking cognitive enhancing drugs and has no tremors and is alert. Which would you prefer to operate?”

The other side of the coin is the coercive element that emerges with the use of smart drugs, with students feeling pressurised to take them to keep up with their peers for example. And with no prospect of insurance coverage - meaning cognitive enhancers will have to be paid for out-of-pocket - their emergence raises issues about a two-tier society.

These are all important questions that need to be addressed, and it is encouraging that debate about the use of smart drugs and other human enhancement technologies is getting underway.  

A report on the very topic written by experts from the Royal Society, the Royal Academy of Engineering, the British Academy and the Academy of Medical Sciences and published last year sums the challenge up perfectly: 'If any enhancement is seen as valuable, scientists need to work together with social scientists, philosophers, ethicists, policy-makers and the public to discuss the ethical and moral consequences of enhancement, and thus to harness maximum benefit with minimal harm.'

Article by
Phil Taylor

freelance journalist specialising in the pharmaceutical industry

18th June 2013

From: Research, Sales, Healthcare



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