All on the mind
May 22nd 2008
From The Economist print edition
Prepare for drugs that will improve memory, concentration and learning
FOR thousands of years, people have sought substances that they hoped would boost their mental powers and their stamina. Leaves, roots and fruit have been chewed, brewed and smoked in a quest to expand the mind. That search continues today, with the difference only that the shamans work in pharmaceutical laboratories rather than forests. If asked why, the shamans reply that they are looking for drugs to treat the effects of Alzheimer's disease, attention-deficit disorder, strokes, and the dementias associated with Parkinson's disease and schizophrenia—and that is the truth. But by creating compounds that benefit the sick, they are offering a mental boost to the healthy, too.
Such drugs are known as cognition enhancers. They work on the neural processes that underlie such mental activities as attention, perception, learning, memory, language, planning and decision-making, usually by altering the balance of the chemical neurotransmitters involved in these processes. This week a report* from the Academy of Medical Sciences, a British learned society, says that a large number of such brain-affecting drugs are likely to emerge over the next few decades. Sir Gabriel Horn, a researcher at Cambridge University who chaired the group that produced the report, reckons that scientists are working on more than 600 drugs for neurological disorders.
History suggests that most of these will fall by the regulatory wayside, but given their numbers, a fair few are likely to be approved. And although none of the companies working on cognition-enhancing drugs designed to treat illness intends to license them for wider use, that is what is likely to happen—at least going by the growing “off-label” use of existing drugs such as Ritalin (methylphenidate) and Provigil (modafinil) by people who want to pep themselves up.
Provigil and Ritalin really do enhance cognition in healthy people. Provigil, for example, adds the ability to remember an extra digit or so to an individual's working memory (most people can hold seven random digits in their memory, but have difficulty with eight). It also improves people's performance in tests of their ability to plan. Because of such positive effects on normal people, says the report, there is growing use of these drugs to stave off fatigue, help shift-workers, boost exam performance and aid recovery from the effects of long-distance flights.
Earlier this year, Nature, one of the world's leading scientific journals, carried out an informal survey of its (mostly scientific) readers. One in five of the 1,400 people who responded said they had taken Ritalin, Provigil or beta blockers (drugs that can have an anti-anxiety effect) for non-medical reasons. They used them to stimulate focus, concentration or memory. Of that one in five, 62% had taken Ritalin and 44% Provigil. Most users had somehow obtained their drugs on prescription or else bought them over the internet.
Given results like this, and the number of drugs of this kind that look likely to emerge, many people, including the authors of the report, believe that the use of cognition-enhancing drugs is going to grow a lot.
There are a number of approaches to cognition enhancement. One of them, according to Trevor Robbins, a colleague of Sir Gabriel's at Cambridge and another member of the working group, is to activate the brain's “off” and “on” switches. Crudely put, the brain's neural networks can be thought of as electrical circuits. Neurotransmitters throw the switches.
Thanks for the memory
One such neurotransmitter is glutamate. This throws switches to the “on” position in memory-forming circuits. Members of a newly discovered class of compounds, ampakines, boost the activity of glutamate and thus make it easier to form memories.
Cortex Pharmaceuticals, based in Irvine, California, is one firm that is developing ampakine drugs. One of its compounds, code-named CX717 to disguise its exact identity, is undergoing testing for Alzheimer's disease in elderly patients. Early trials have already shown that the drug can make people more alert. Unlike caffeine, amphetamines and other stimulants, CX717 causes no increase in blood pressure or heart rate. Nor does it offer any “high”, so is unlikely to be addictive.
Paradoxically, another glutamate-booster, D-cycloserine, is being tested not to enhance memory, but to abolish it. The paradox is resolved because unlearning (or “extinction”, in neurological parlance) is a process similar in its details to learning.
By binding to certain glutamate receptors, D-cycloserine selectively enhances extinction, suppressing the effects of conditioned associations such as anxiety, addiction and phobias. According to Dr Robbins, experiments have shown that if a rat is given a cue that it previously associated with fear at the same time as it receives D-cycloserine, the bad memory can be eliminated. Not only may this help remove unpleasant memories, such as those involved in post-traumatic stress disorder, but it may also help to return the brains of addicts to their pre-addicted states. It may, for example, be able to remove the triggers that cause smoking.
Another approach to cognitive enhancement, says Dr Robbins, is through a neurotransmitter called acetylcholine. Cholinergic neurons—the name for those that respond to this molecule—are involved in concentration, focus and high-order thought processes, as well as memory. It is the cholinergic system that degenerates in Alzheimer's disease.
Interest has thus focused on drugs that inhibit the breakdown of acetylcholine, and also on nicotine, which works by mimicking its effect. Dr Robbins says that cholinergic drugs may offer minor cognitive benefits for things like alertness, and similar drugs could be “potentially useful in normal humans”.
Mind-expansion may soon, therefore, become big business. Even though the drugs have been developed to treat disease, it will be hard to prevent their use by the healthy. Nor, if they are without bad side-effects, is there much reason to. And if that is so, there may be a very positive side-effect on the profits of their makers.
* “Brain science, addiction and drugs”. The Academy of Medical Sciences, 10 Carlton House Terrace, London SW1Y 5AH
May 22nd 2008
From The Economist print edition
Drugs to make you cleverer are in the test-tube. Good
THIS drug is peddled on every street corner in America, and is found in every country in the world. It is psychoactive, a stimulant and addictive. Users say that it increases alertness and focus, and reduces fatigue. But the high does not last and addicts must keep consuming it in increasing quantities.
Put this way, sipping coffee sounds more like an abomination than the world's most accepted form of drug abuse. But centuries of familiarity have put people at their ease. In the coming years science is likely to create many novel drugs that boost memory, concentration and planning. These may well be less harmful than coffee—and will almost certainly be more useful. But will people treat them with as much tolerance?
The new cognition-enhancing drugs are designed to treat debilitating diseases such as Alzheimer's, attention-deficit disorder and schizophrenia. But because they act deep in neural pathways of the brain, some of them are bound also to enhance people's power to think and learn (see article). Such drugs will inevitably be used by healthy people too. That is the lesson from medicines such as Ritalin (methylphenidate) and Provigil (modafinil), which are now widely used “off label” to boost performance, as Nature has found. When the British journal asked its scientifically aware readers earlier this year, one in five of those who answered said they had used such drugs non-medically, to help them concentrate or learn.
For many, drug is a four-letter word. Unapproved use is at best worrying and unfair, and at worst dangerous and immoral. Such thinking leads to strict controls or even prohibition and criminalisation. In Britain, for instance, Ritalin is a class B drug. Yet strict controls would be both futile and wrong.
Futile, because if people really want medicines, they can easily get hold of them. Nature's drug users procured their stashes from prescriptions from doctors or over the internet. As anyone with an e-mail address knows, the difficulty is not scarcity, but keeping the offers for Viagra, real or fake, at bay.
And wrong because such drugs promise to do a lot of good. Many people already use Provigil to cope with night-shift work, jet lag and lack of sleep, and suffer few side-effects. Others use beta-blockers to overcome the anxiety and stress of performance. Scientists use off-label drugs to increase their focus. If that helps them unravel the mysteries of the universe, so much the better. If chemical assistance can help increase the useful human lifespan, the benefits could be huge.
Some worry about the unfair advantage and peer pressure that comes from these drugs. However, millions suffer from untreated but mild memory loss. Is it fair to deny them help? If the shy or the scatterbrained take cognitive enhancers, it is not obvious whether this is levelling their playing field or giving them an unfair advantage. Is it “natural” to prop up the ageing body with a nip and a tuck, but to restrict help for the ageing mind to brain-training on the Nintendo?
Punishing the off-label use of cognitive enhancers may also be unfair to those who find these drugs medically useful in unexpected ways. Schizophrenics, it has recently been found, are likely to be heavy smokers because nicotine is good for their condition. Genetic variations between people are associated with different levels of working memory. People using Provigil or Ritalin may eventually be found to have a legitimate but previously unknown need for the drug.
There will always be risks, but no more than for other medicines. Remember that the new drugs will have passed clinical trials because they are treatments for a disease, even if they have not been licensed as cognitive enhancers. There will be a lot of habitual off-label takers, more people than in the trials, so the regulators need to monitor them for side-effects—especially in children. But detailed and accessible information about the side-effects of drugs is to everyone's advantage.
With any compound, the task is to minimise harm while maximising the freedom to choose. It may even be that, like Viagra, society largely welcomes the arrival of a chemical that does, far better, what omega-3s, ginseng, vitamins and all the other quackery have failed to do. Unless of course, you want to outlaw double espressos too.
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