Nootropics: drugs, application and effectiveness
Neuropsychologist Barbara Sahakyan on the advantages and dangers of using "smart drugs", improving memory and increasing motivation
Nootropics ― these are drugs that improve cognitive abilities. They increase attention, improve learning ability, memory, planning capabilities, decision-making and problem resolution. This is a key feature that distinguishes nootropics from other types of medications. Other medications do not have such an effect, otherwise they will be considered nootropics.
Where are nootropics used
Nootropics are used to improve cognitive skills, functionality and well-being of patients in many areas. Psychiatric disorders such as attention deficit hyperactivity disorder (ADHD), schizophrenia, and depression are cognitive impairments. Cognitive problems in psychiatric disorders include impaired attention, memory, and lack of cognitive control of the prefrontal cortex. There are also cognitive neurodegenerative disorders, such as Alzheimer's, Parkinson's and Huntington's disease. People suffering from traumatic brain injuries also have cognitive problems. It is such patients who are helped by nootropics.
Some of the drugs are also used to improve the quality of life of healthy people, which leads us to neuroethical problems and the question of how society sees itself and what is our path to maintaining good cognitive abilities and mental well-being. How do we want to develop this area and what goals do we want to achieve?
Barbara Sahakyan on her research on Alzheimer's disease
My story began a long time ago: I opened some of the first memory clinics – one in America with David Drachman many years ago, and another at the Institute of Psychiatry with Raymond Levy and Michael Philpot. These clinics were supposed to help detect Alzheimer's disease in the early stages. To do this, we have developed one of the first, very good tools – CANTAB tests, which are carried out on touch screens. We knew that good drugs could help with the treatment of cognitive impairments such as approaching memory problems, but we needed to find people who had these problems in the early stages.
Our task was to find good tools to resist neuropathological changes. In Alzheimer's disease, amyloid plaques and neurofibrillary tangles (clusters of protein) appear in various parts of the brain, mainly in the hippocampal formation (this is the area of the brain behind the ears). Plaques and tangles are neuropathological changes that disrupt memory functions.
Currently, neuropharmaceutical companies are developing drugs that we call neuroprotective agents. They can restrain the underlying processes of the disease. But before they appeared, cholinesterase inhibitors were used. These drugs act by increasing the level of acetylcholine in the brain, and as a result improve the concentration and attention of people with Alzheimer's disease. Many years ago, we published in The Lancet a study to test the concept of these cholinesterase inhibitors for patients with Alzheimer's disease and were able to show significant improvements in concentration and attention, but, unfortunately, could not show sufficiently serious improvements in episodic memory.
Nootropics: drugs and effects on the body
One of the commonly used cognitive enhancement drugs is methylphenidate, also known as ritalin, and modafinil.
Methylphenidate increases the synaptic concentration of dopamine and norepinephrine by blocking their reabsorption.
Modafinil has many actions, including indirect mediation of the activity of cholinergic receptors and/or alpha-1 adrenoreceptors. Modafinil affects hypothalamic orexin and histamine and has a small effect on dopamine transport activity. Recent evidence suggests that modafinil affects the mechanisms of norepinephrine, dopamine and glutamatergic.
Dopamine, norepinephrine and glutamate are important for learning; dopamine is also important for motivation.
Modafinil has been approved by the FDA in the United States and the United Kingdom for the treatment of narcolepsy – attacks of irresistible daytime sleepiness. In the USA, this drug has another indication for use – sleep disorders caused by shift work, as it has been found that it reduces the number of accidents in people working in shifts.
We also considered modafinil as an adjunct to antipsychotic medications for people with the first attacks of psychosis or schizophrenia. Patients suffering from schizophrenia have psychotic symptoms – hallucinations and delusions. Antipsychotic drugs known to us (drugs that block D2 receptors) cope well with these psychotic symptoms. But cognitive impairments of patients with schizophrenia, as well as problems with motivation, known as negative symptoms, are not treated very well.
The U.S. Food and Drug Administration realized that an important part of treating people with schizophrenia is improving their cognitive abilities. They found that they had problems with rehabilitation. For example, if you are a student and you have been diagnosed with schizophrenia, it may be difficult to return to university and focus on your studies. Or if you are working and you have been diagnosed with this, then it may be difficult for you to return to work. These are all cognitive problems.
So, the government realized that the biggest obstacle to rehabilitation is cognitive problems and that they need to be treated. But at the moment we don't have any approved drugs. In our projects in Cambridge, in my laboratory, we used cognitive training, gamified this method, and were able to improve the cognitive functions of people with schizophrenia – including improving their episodic memory – with the help of games. But we also tried to improve their cognitive abilities by prescribing them modafinil. We found that it causes positive changes, improvements in working memory – a very important type of memory associated with executive functions, such as, for example, planning or solving tasks that you face at university or at work. Modafinil has an effect on norepinephrine, dopamine, and also affects the balance of GABA and glutamic acid and even, possibly, directly affects glutamic acid. Thus, according to our hypothesis, this drug provides an improvement in cognitive functions.
During our studies of patients with schizophrenia, as well as other groups of patients, for example, with depression, we found that modafinil can be an effective drug for improving cognitive functions. It also affects the motivation associated with performing tasks that seem unpleasant or not very interesting, that is, to some extent increases performance.
Effectiveness of nootropics
There are many controversial claims about the effectiveness of nootropics that are not supported by evidence. Nevertheless, it is important that there is also published evidence demonstrating that a drug claiming to have the effect of increasing cognitive abilities actually increases them. This has been demonstrated through experiments using a double-blind method and a controlled placebo. There is also one of our studies of modafinil (Muller et al., Effects of modafinil on non-verbal cognition, task enjoyment and creative thinking in healthy volunteers), improving cognitive abilities in a group of healthy volunteers. You can see for yourself by reading about it in scientific articles.
Neuroethics: is it worth improving the cognitive abilities of healthy people?
Our society has realized the effectiveness of "smart medicines". People who have no health problems started using them. They make this decision for three main reasons. Firstly, healthy people want to gain an advantage over competitors at university, at work or at school, to enroll in the best university. The second reason is the desire to stay awake and focused longer. For example, I asked my fellow teachers, and many of them used these drugs to cope with jet lag syndrome. And in large cities, people use nootropics because they need to work longer and they want to stay awake and focused. The third reason is to perform tasks that people constantly postpone and that do not inspire enough motivation to take on them: the drug helps people to take on a task and complete it. In the context of clinical treatment, I think if we can combine some of these nootropic drugs with cognitive training in the format of games, we will most likely get the greatest possible improvement in the cognitive abilities of people with neuropsychiatric disorders and brain injuries.
Part of my concern about healthy people using nootropic drugs is primarily related to safety issues. We have no long-term studies showing that these drugs are safe for healthy people. So we really need to do research before healthy people can take nootropics. The second question that worries me is that these drugs are difficult to get and because of this, people buy them over the Internet, and this is an extremely dangerous way to get prescription-only drugs. You don't know what you're buying, it could be anything. If you take another medicine, you may get drug interactions, and this can be very dangerous. So we have to take that into account. And the third question that causes me concern is more social, related to issues of neuroethics.
In his book “Bad Moves” (Sahakian & Labuzetta, Oxford University Press, 2013) I consider many ethical issues. An important question is about the cost of nootropics and their availability. It is possible that only rich people will be able to afford to buy them, and, as a result, the social gap will increase. This question has already been raised in the article “Towards responsible use of cognitive-enhancing drugs by the healthy”, which was written by my colleagues and me.
Another problem is coercion. Many students have told me that they do not want to take "smart medicines", but they feel pressure from the outside, because they know that other students at the university are taking them, and are concerned that they will not be able to compete in these conditions.
As a society, we need to understand why healthy people feel the need to take such medications. In addition, now we know that the brain continues to develop in adolescents and young adults, and therefore there is a question of what the effect of using such drugs will be in a healthy and developing organism.
It is necessary to think: what kind of society are we creating? Will we take nootropic drugs in the future in order to create a better work-life balance, do work in a shorter period of time and, perhaps, unlock other potentials: spend more time with family, get lifelong education, allocate more leisure time to enjoy life? Or will we just turn into a 24/7 society and work all the time just because we can work all the time?
Society is already subject to enormous stress, some of which is caused by globalization and more and more pressure on people at work. This is one of the reasons why people take these drugs – to cope with the demands at work. As a society, we need to think about how we want to improve our cognitive abilities. Exercise is an amazing way to improve brain function, and besides, it improves mood and is good for physical health. So I recommend exercise as one of the ways to improve cognitive abilities for healthy people. Although we really need to develop new types of nootropic drugs that are more effective and safe for people with neuropsychiatric disorders and brain injuries.
The Future of nootropics
The use of nootropics and drugs that increase cognitive abilities is increasing. I think this trend will continue. That is why it is so important to conduct long-term studies of the safety and effectiveness of such drugs for healthy people. The government should team up with the pharmaceutical industry to conduct research to determine whether modafinil really improves cognitive abilities in healthy people in the long term and how safe it is to take it for a long period of time.
As already mentioned, many people use such drugs to gain competitive advantages, others – to overcome sleep deprivation or jetlag. And modafinil improves motivation to complete tasks, therefore, work that seems boring or difficult turns into more enjoyable if you take it. At the same time, he did not have the potential to form an addiction, he does not produce euphoria.
Modern clinical studies of nootropics
Important clinical trials of modafinil are currently underway. Some of them can be viewed on the website of the US National Institutes of Health (National Institutes of Health), in particular on the website of the National Institute on Drug Abuse (National Institute on Drug Abuse). Anyway, the studies that are known to me relate to the study of groups of patients. As far as I know, there are currently no long-term studies on the safety and effectiveness of nootropics in healthy people.
About the author:
Barbara Sahakian – FMedSci, DSc, Professor, Department of Psychiatry, Behavioural and Clinical Neuroscience Institute, Cambridge Centre for Brain Repair, Wolfson Brain Imaging Centre, University of Cambridge.
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27.06.2017