Cognitive-Enhancing Drugs

The video is a part of the project British Scientists produced in collaboration between Serious Science and the British Council.

Good brain health and mental well-being are the biggest challenges of the 21st century. How do we keep our minds functioning better throughout our life course, especially now that we are living longer? And also, how do we have a good sense of mental well-being? These are two topics with the focus of the UK government Foresight project on Mental Capital and Well-being, because the government wanted to address two important problems that we have. The first problem was that we are living for longer, and age is a big risk factor for Alzheimer’s disease. So, as we get older we have to keep our brains fit and to have a good cognition and well-being throughout the whole life course, which may be these days up to 90 or 100 years age. The other concern they had was that the government and businesses were losing a lot of money due to days lost at work, due to depression. So, how can we keep a good sense of well-being throughout the life course? In that project we looked to both promoting factors for good brain health and well-being and those are such things as good education. And we looked at detracting factors for good brain health, and also such things as stress, substance abuse and all sorts of things.

Now, my own work has focused on how we can enhance our cognitive function and also our well-being, our motivation. And during the course of that work which my work mainly focuses on neuropsychiatric disorders, such as Alzheimer’s disease, Attention-deficit/hyperactivity disorder, where we have some good cognitive-enhancing drugs, but in the process of doing that work I’ve also been involved in the interaction of neuroscience with society, we call this neuroethics. So, I’ll just explain a little bit about the field and also about my own research to try to highlight the importance of the area and the drugs that we have, that we can use to boost cognition in people who need boost such as those with cognitive impairments due to neuropsychiatric disorders or brain injury, but also about the increasing lifestyle use of some of these drugs by healthy people which brings us to neuroethical issues and how we see ourselves as a society and how do we see ourselves moving foward to make sure that we have good cognition and well-being. In what ways do we want to develop that and how do we want to achieve that goal?

My story starts a long time ago. I opened up some of the first memory clinics: one in America with David Drachman many years ago and also at the Institute of Psychiatry with Raymond Levy and Michael Philpot. These memory clinics were to help to do an early detection of Alzheimer’s disease. We actually aslo developed some of the first very good tools for the early detection of Alzheimer’s disease, these are called CANTAB tests. And I am a co-inventor of these tests, which run on the touch-sensitive screen. And the reason they were developed was because we didn’t have very good tools for the early detection of the memory problems and Alzheimer’s disease. We knew there was a possibility of good drugs to treat such cognitive impairments such as a memory problems on the horizon. But we needed to detect people who had these problems so early on, because as you may know in Alzheimer’s disease there are plaques and tangles in areas of the brain, particularly starting in the hippocampal formation area, the kind of area behind your ear. And those plaques and tangles actually are the neuropathological changes, which impair memory function.

So we needed to find good ways to counteract the neuropathological changes that we see in the brain and to try to promote that better. Now pharmaceutical companies are developing what we call neuroprotective agents. And these drugs will actually hold the underlying disease process. But before we had those, we had what we call the cholinesterase inhibitor drugs. Those drugs act by boosting a chemical in the brain called acetylcholine. And what it does is to improve concentration and attention in people with Alzheimer’s disease. In our own studies, which we published in The Lancet many years ago, these are proof-of-concept studies for these cholinesterase inhibitor drugs in patients with mild and moderate Alzheimer’s disease, we were able to show good improvements in concentration and attention, but unfortunately we couldn’t see really good improvements in episodic memory.

Episodic memory is the type of memory that we use every day. So, for instance, if you park your car in a multistorey car park and then you have to remember “Oh, where you did I leave my car”, it’s that type of memory. Or, if you sort of rush into your house, open the door with your keys and then throw the keys somewhere and a few hours later you’re deciding to leave the house and you think “Oh, where did I leave my key” and you try to remember where they are. That’s episodic memory. So you could see, we use it every day. And if it was impaired it would be very difficult to function. And we’ve actually shown that CANTAB PAL test is very strongly related to functional outcome and can be used on an iPad for early detection of memory problems in the clinic.

So, what we have are the cholinesterase inhibitor drugs, also drugs known as Aricept or Donepezil and other types of drugs like that. And they essentially boost acetylcholine in the brain. In ADHD we’ve been using stimulant drugs, also known as amphetamines (e.g. Adderall) and we’ve also been using methylphenidate (e.g. Ritalin). These drugs, in particular Ritalin, is a very effective treatment for ADHD. It works in about 70% of patients to help them function on a daily basis and it seems to help them with sustained attention, which is the major problem they have. So, we use again some of the CANTAB tests in the clinic to assess how well they can actually sustain their attention. We use the test called Rapid Visual Information Processing (RVP) task and we find that we do get very good effects looking at the effects of methylphenidate on that task. And it does seem to improve performings greatly. Now, the interesting thing is when we look at the effects of methylphenidate in healthy people we also see improvements. So, these drugs aren’t just working on people who have problems in cognition due to neuropsychiatric disorders. They also seem to improve cognitive function in healthy people.

More recently, we’ve been working with the drug called Modafinil. Modafinil is actually approved by FDA in America as well as over here in UK for the treatment of narcolepsy, which is excessive daytime sleepiness. In the USA it also got another indication, and that indication is for sleep disturbance caused by shift work, because modafinil has been found to reduce accidents in people, who were shift-workers. And we’ve been looking at modafinil as an add-on to antipsychotic medication for people with, say, First Episode Psychosis or schizophrenia. So, in people with schizophrenia there are three separate problems. We have the psychotic symptoms, which are the hallucinations and delusions. Hallucinations are the hearing of voices, delusions are the abnormal thoughts, unusual thoughts that people have. Those psychotic symptoms are reasonably well treated by the antipsychotic drugs (D2 receptor blockers) that we have. But what is not well treated are the cognitive problems that schizophrenia patients have, and also the motivational problems, sometimes known as negative symptoms, that schizophrenia patients have.

The FDA has realized that the important part of the treatment of people with schizophrenia would be to boost their cognition because they’ve actually decided that they have problems with rehabilitation, e.g. if you are student and you were diagnosed with schizophrenia, it is sometimes difficult to get back to University and focus on your studies of if you’d been diagnosed at work and then you find it difficult to actually engage again with your work and to learn new things in the work environment. These are cognitive problems some people have. So, the governments have realized that the biggest barrier to rehabilitation is actually the cognitive problems. And these need a treatment. But as yet we don’t have any approved drug treatment. With our projects here in Cambridge, in my laboratory, we’ve actually been using cognitive training but gamifying it, so that we could improve cognition in people with schizophrenia, improve, for instance, their episodic memory using games. But another thing that we’ve tried to do is to enhance their cognition by adding on Modafinil. And what we found there is that we do get very good changes, improvements in working memory, which is a very important kind of memory, dealing with executive function tasks, such as, for example, planning or solving problems at University or at work. And this drug, Modafinil, seems to act on noradrenalin, dopamine, but also it seems to affect the GABA—glutamate balance and maybe even affect glutamate directly. And that is how we think it causes cognitive enhancement effects.

In the course of our studies with patients with schizophrenia and also in another groups of patients we were looking at depression we found that Modafinil can be an effective cognitive enhancing drug for these people. It also affects task-related motivation. So, for tasks that we found unenjoyable or not very interesting for people it seems to make people more motivated to do them, which means to some extend it is an interesting workplace drug. Individuals in our society have been realizing this and healthy people have decided to use this drug. And when I found out why people decide to use this, it seems to be for three main reasons. One — healthy people want to get competitive advantage at University or work or school or get into better University. The second reason seems to be to stay awake and alert for longer periods of time. So, for instance, many of the academic colleagues that I have used it to count out the effects of jet lag when I’ve spoken to them. And in a city people use it because they have to work longer and they want to stay awake and alert. People in Silicon Valley are using some of these cognitive-enhancing drugs too. And then the third reason seems to be that for the task that people have been putting off and have not found motivated to do. It helps them to get into the task and to do it. In terms of clinical treatments I think if we can combine some of these cognitive-enhancing drugs with such things as cognitive training using games which are motivating and fun, we will probably get the best boost out of cognition for people with neuropsychiatric disorders and brain injury.

Some of my concerns about using these cognitive-enhancing drugs in healthy people are really first of all the safety issues. We have no long-term studies in healthy people showing that these drugs are safe. So, we really need those studies before healthy people can use these cognitive-enhancing drugs. The second thing I am concerned about is because they are difficult to access people are buying these drugs over the internet. And this is an incredibly dangerous way to get prescription-only medications. So, you don’t really know what you are buying, it could be anything. And if you are taking another medication, you get a drug-drug interaction, that could very dangerous. So we have to be concerned about that. And my third concern is a more of a societal, neuroethical issue.

I mean, what kind of a society we are developing into? Would we take these cognitive-enhancing drugs in the future, so that we could have a better work-life balance, have our work done in a shorter period of time, and maybe expand ourselves by spending more time with our families and maybe going to lifelong education or something like that, have more leisure time so we’ll be able to enjoy ourselves? Will we get a better work-life balance using these drugs in the future if we know that they are safe? Or will we just accelerate into a 24/7 society and we will work all the time because we can work all the time. And there is already so much stress in society, some of this is being caused by globalization and more and more pressure on people for long working hours. So this is one reason why people are taking these drugs to kind of cope with some of the demands at work. And as a society we have to think on how do we want to boost our cognition. Exercises are fantastic way to boost your brain power. And also of course, it is good for your mood and it is good for your physical health. So, I highly recommend exercises as a good way for healthy people to boost their cognition. But we do need to develop some more of these cognitive-enhancing drugs, more effective ones and obviously safe ones for people with neuropsychiatric disorders and brain injury.