Cognition Enhancing Drugs

21 November 2010

Interview with

Charlotte Housden, Cambridge University

Chris -   This week, we're looking into brain boosting or so-called smart drugs.  Joining us to explain what they are and how they work is Cambridge University's Charlotte Housden.  Hello, Charlotte.

Charlotte -   Hello, Chris.  Hi.

Chris -   Welcome to the program.  What do we actually mean by cognition in the first place and a cognition boost?  What actually is this?

Charlotte -   Cognition can be thought of as a basic mental processing function that's essential for every day behaviour and activity; such as memory or attention.  And then these general areas of cognition can actually be divided up even further, so you've got different kinds of memory:  working memory, long term memory, and these are all associated with different areas of the brain.

A Student of the University of British Columbia studying for final examsChris -   And how much do we understand about how the brain actually does those jobs in order to develop drugs that change them?  Or most of these drug interventions done blindly in terms of - we find something that works, so we use it.

Charlotte -   It's a mixture of those approaches actually so sometimes you have a drug and then we find it worked with a certain patient group, and that can tell you something about how the drug is working, that can open up doors on further potential treatments, and that's the more usual approach.  Or we can have a good idea around what's going on with a certain patient group and then go looking for drugs that would help them.

Chris -   Where are we with this at the moment when we're saying we have drugs?  We know people on campuses, in laboratories, in business board meeting are using these things because people have done studies published in pretty powerful journals where people are blindly and anonymously saying, "Yes, I'm using these things."  What's the scale of the use though, do you think?

Charlotte -   It's quite hard to say, but just as an indication of the use of these drugs by healthy people, the Cambridge University student newspaper did a survey last year and they interviewed a thousand students, and they found actually 10% of students admitted to using a drug to help them with their studies.  The reasons they gave were to improve concentration, and also, to enable them to have a work life balance.

Chris -   I'd quite like that!  But what are we classing as a drug?  Would they be answering, "I'm on a drug" if they said, "I had 15 cups of very strong coffee a day."

Charlotte -   Well, for the people who answered the survey in this particular case, we're just talking about actual drugs.  But it's interesting you brought up caffeine because actually, caffeine is a mild stimulant and is something that lots of people use to improve their cognitive ability.  It has been shown to improve memory and attention in people who are sleep-deprived, so it's a wake promoting drug that lots of people turn to.

Chris -   Although as one person put it to me, you're never quite clear whether it's just people getting relief from the side effects of caffeine deprivation, making them feel so much better that their performance improves, which I think is probably the case with me, compared with actually having some kind of tangible improvement on what your baseline would be.  People have presumably done that;  they've taken people who were not caffeine users and then put them on it and seen a demonstrable improvement.

Charlotte -   Yes.  So there have been double-blind studies with drugs such as caffeine, particularly in sleep-deprived people, it seems to have an effect.  So it seems that caffeine's cognitive enhancing effects are related to its wake promoting properties.  So caffeine would probably be best when you're feeling a bit tired.  But actually, if you're performing quite well, the effects might not be quite as big as if you were sleep-deprived.

Chris -   Well caffeine, that's common and lots of people use that quite legally - I'm one of them.  What about the other things that people use illicitly though?  What sort of drugs fit in to that category, that boost brain power?

Charlotte -   Well, there are other drugs which have originally been developed for use in patient populations.  So, from my point of view, I'm interested in investigating how drugs such as these can be used to help patients with cognitive impairments.  These drugs are being used by other people, and they include drugs such modafinil which is known as Provigil, which have been shown to improve cognition in healthy people.  And again, it was originally developed for use in patients with narcolepsy.  So again, it has wake promoting properties and it's also recently been licensed for use in shift work sleep disorder, so for people who aren't performing well because they're tired.

Chris -   So when you're taking these agents, the research you do, presumably what you do is to put people into a brain scanner and put them either on the agent or on a placebo and give them a trial to do some kind of cognitive workout in order to compare how the brain is performing under those conditions.  What does it do to the nervous system when you take these agents?  In what way is it achieving these beneficial effects?  I know you've said that it obviously wakes people up a bit, but is there something else beyond that?

Charlotte -   Okay, so if I use modafinil as an example, we've done cognitive tests with modafinil in Cambridge and we've found that modafinil in healthy people in Cambridge, healthy young adults with high intelligence, actually showed improvements on working memory and also response inhibition.  So that's the ability to stop yourself automatically responding to an appropriate stimuli, which is actually quite a useful cognitive skill.  

Chris -   So people become less distractible?

Charlotte -   Yes, in a way or less impulsive.  Modafinil seems to work through a few different neurotransmitter systems.  It doesn't just focus on one system, so something which lots of people might have heard of is dopamine.  It seems to bind very weakly to dopamine transporters so that increases throughout the brain.  It increases dopamine in a kind of tonic way rather than dopamine firing.  It's a diffused increase in dopamine and it also seems to affect noradrenalin glutamate systems.  And the way that modafinil actually makes people more alert is it helps more sensory information get to the prefrontal cortex which happens when you're feeling quite awake and the prefrontal cortex is a nerve of the brain that's really important for high level cognition, so we call them executive functions.  These are things that such as thinking flexibly, planning and problem solving, things that are quite high level.

Chris -   But the thing that strikes me is that if you take this agent and you get these effects, if they were beneficial, why wouldn't your brain already have those pathways and those levels of neurotransmitters normally?  Why should it be beneficial to enhance them in this way if it were good for you in the long run?

Charlotte -   Okay, so actually, we all have different levels of neurotransmitters in our brains.  Everybody has different levels and different levels are actually advantageous for different things, and actually, these drugs do work differently in different people.  That's something very important to keep in mind.  A drug that might enhance cognition in somebody may actually impair cognition in somebody else.  So, I talked about the prefrontal cortex being really important and actually, with dopamine in the prefrontal cortex, you want to kind of have an intermediate level of dopamine there, for you to be functioning at your best.  And some people have a naturally lower level of dopamine than others, so if they took a drug that improved dopamine, then the functions associated with the prefrontal cortex get better, such as working memory.  However, if you naturally have quite high levels of dopamine, you're a high functioning person, your memory is quite good, then actually, taking a drug like modafinil would actually make you perform worse on a working memory task.

Chris -   Or you might think you're performing better, presumably, do some students who take this stuff and it makes them wake up because of the action on other neurotransmitters, suffer a benefit in one regard, but a disbenefit in the other?

Person solving Finnish crossword puzzleCharlotte -   It could potentially work like that.  So as I've said, modafinil works on a few different systems. Yyou could be seeing benefits in some areas and not others.  And actually, the amount of the drug that people take also influences that, so say for instance, another drug, methylphenidate which acts on dopamine systems.  When people with ADHD take this drug, their attention or levels go up as their dose increases, but actually, at high levels people become more impulsive.  So you've got to balance this out with the dose and it also depends on your individual genetic makeup as well.

Chris -   What about the long term effects, Charlotte?  Presumably, we haven't been using these agents for long enough to know about a lifetime's use of this in the workplace.  What will that do to my brain eventually?  Will I end up rotting out my brain, whereby I have to take this stuff, just to function normally?

Charlotte -   Yes, so that's an interesting concept.  It's quite difficult to know at the moment because we found it quite hard to get ethical approval to do studies in healthy people for long term use, just because if it is detrimental, then it's not very good to do that to people in your studies.  All of the drugs that people are using off-label, have been licensed for use and safe use in patient populations, so that's one thing.  There is a problem with long term use of drugs that are bought on the internet because actually, there's no guarantee that they're safe and actually, most internet sites will give you the drugs without a doctor's prescription.

Chris -   And that's where the students are getting it from, is it?

Charlotte -   There is different research saying different things, so yes, lots of people do get them off the internet and you don't need a doctor's prescription for that, which is quite worrying because you don't actually know what you're buying.  And there's also a problem with people selling drugs prescribed to them, to others, people obtaining drugs that are given to relatives or friends for their own cognitive impairments.

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