A trip down memory lane

Drugs specifically designed to improve the memory of Alzheimer's sufferers will soon be on the market. What is to stop students, some of whom already buy 'smart' drugs on the Internet, using them too? Graham Lawton reports

Something like 300,000 Americans, many of them students, regularly take drugs they believe will make them more intelligent. The substances they use - so-called "smart drugs" - are available in health food stores, in clubs and bars and via mail order addresses on the Internet. Like body builders guzzling anabolic steroids they are willing to risk their health in an attempt to build up their intellectual muscle.

The potential gains are evident - improving memory could, most obviously, boost exam performance or - more trivially, ensure success on University Challenge. Likewise, the range of substances available is enormous. Many of them are prescriptive drugs designed for other purposes. All of them are being used without clinical approval, medical supervision or scientific backing.

Scientists despair of smart drug users. "The smart drug claims are not based on solid science but wishful thinking at best," says James McGaugh, director of the Center for the Neurobiology of Learning and Memory at the University of California.

But that is about to change. Recent scientific advances mean that drugs specifically designed to enhance memory will soon be available. The new drugs are targeted at people with failing memories and, provided they are safe, will hugely improve their quality of life. For people afflicted by Alzheimer's disease, which robs victims of their minds, obliterates personalities, memories and powers of reason, they will bring a new lease of life.

"If we could postpone dementia for five years then the number of cases would be cut by 50 per cent", says Anthea Tinker of the Age Concern Institute of Gerontology at King's College London. With 600,000-800,000 Alzheimer's sufferers in the United Kingdom alone - the number is likely to double in the next 20 years - there is a desperate need for effective treatments.

But before the Utopia of dementia-free-old age can be realised the problem of nonmedical use will have to be negotiated. At a conference this week at the CIBA foundation in London the issue was openly debated for the first time by all the parties involved. Organised by Stephen Rose of the Open University the event brought together neuroscientists, Alzheimer's researchers, pharmaceutical companies, gerontologists, sociologists, ethicists and legal experts.

Jim Edwardson of the Medical Research Council's neurochemical pathology unit at Newcastle General Hospital, one of the participants at this week's conference, is deeply concerned about young, healthy people taking memory enhancers. He points out that the drugs are designed specifically for dementia and will have no effect on the brains of healthy students. "If these are not described properly by the media," he says, "it may give the impression that they work on people with no memory impairment."

Edwardson's warnings are echoed throughout the medical and scientific community but there is plenty of evidence that they will have little impact. Enthusiasts have a voracious appetite for any drug that is rumoured to have a mind-enhancing effect. Several mail order companies, for example, push Amphotericin, a highly toxic antifungal agent with no proven cognitive effect. The drug is fairly cheap - around three months' worth of Amphotericin (160 250mg tablets) is available for $85, according to sites listing drug prices and order forms posted on the Internet. Against this background it is hard to imagine that drugs specifically designed to improve memory will not attract the attention of casual users.

Some researchers have woken up to the fact that nonmedical use of these drugs is an inevitable corollary of their development. Mary Childs of the faculty of law at Manchester University says the risks must be addressed before the drugs hit the market. Childs points out that the use of cognitive drugs, both for medical and nonmedical purposes, raises a series of legal questions. Are we going to allow drug testing? How do you obtain informed consent from Alzheimer's patients to administer the drugs? And how are we going to deal with recreational users? Would it be right, for example, to penalise people who drive or operate machinery in a state of enhanced cognition? What would happen if employers started to demand that their workers take smart drugs?

"We need to look at the background of recreational, nonmedical drug law in order to suggest where these drugs might fit in," Childs says. "We need to think about whether we might want to treat them as recreational drugs, whether we need to devise a new system or whether we need a system at all."

Other researchers think the question of recreational use is a distraction. "I see the smart drugs fad as trivialising a very important question," says McGaugh. "Of course, real drugs could well replace the faddish smart drugs for some. But I see that as a very minor issue in relation to the broader issues that we will confront when safe and effective drugs are available for improving memory."

That moment is not far away. A drug called Tacrine has just become the first memory enhancer to win the approval of the US Food and Drug Administration. Tacrine is an Alzheimer's drug. It works by rectifying a signalling problem. The brains of Alzheimer's sufferers are short of a signalling chemical called acetylcholine. The drug inhibits the decay of acetylcholine, allowing the reduced quantities that are present to work harder. Tacrine is only modestly effective. It does not restore normal memory, nor does it slow or prevent sufferers' eventual decline. Some patients enjoy a temporary improvement in cognitive functioning but the drug's side effects can be severe. It induces nausea and diarrhoea and is toxic to the liver.

No one knows whether Tacrine has yet found its way on to the smart drugs scene but it is the first swallow of what will be a long summer. Another drug with a similar action is on the brink of approval and researchers are confident that newer, better drugs will be available soon. One US researcher recently patented a drug that he claims will "give a 70-year-old the memory of a 20-year-old."

The new drugs promise to ameliorate an enormous amount of suffering. Only last week it became publicly known that the novelist and philosopher, Iris Murdoch, was suffering from Alzheimer's, and is finding it difficult to write. It seems inevitable that when such drugs hit the market, healthy people will take them. But recreational use could be a price worth paying for a brighter old age.

'It wakes up your mind'

Despite the scepticism of the scientific community towards the claims of the smart drug faddists their interests occasionally overlap. One of the most popular self-prescribed drugs is Piracetam, a member of the acetam drug family. Piracetam is used to treat several disorders including vertigo, dyslexia, alcoholism, stroke and sickle cell disease but is not intended as a memory enhancer.

Users claim that Piracetam "wakes up your mind" by speeding up the flow of information between the hemispheres of the brain. This kind of woolly claim is typical of smart drug literature and wins few friends in the scientific community. But some scientists and doctors are taking the drug seriously.

Acetams are the subject of intensive research. Their precise action remains obscure but there is some evidence that Piracetam increases the brain's sensitivity to acetylcholine, the neurotransmitter that declines in Alzheimer's disease. Alzheimer's patients in the US often try Piracetam with their physician's blessing.

The efficacy of acetams, however, remains contentious. "They are widely used in Europe but have almost no credence over here," says Jim Edwardson. He suggests that acetams may have no effect on cognition or memory per se - they could act as general metabolic stimulants, producing feelings of enhanced cognitive power, or work via a placebo effect.

Memory formation

One of the things that causes memory to fail is a problem with long-term potentiation (LTP) - the transfer of information from short to long-term memory. Scientists in Stephen Rose's research group at the Open University are working on LTP and their results could have applications in the smart drugs field.

They are investigating the action of a naturally occurring neurochemical, which seems to stimulate parts of the brain where LTP happens. They are also interested in the way that brain cells communicate with each other as short-term memory becomes long term.

Rose's group is interested in the broad pattern of memory formation - from the biochemical and genetic events of learning to the behaviour of animals. Their current focus is on trying to make chicks forget things. "This approach offers potential treatments for memory loss," says Rose.

Another group of chemicals, called ampakines, also seems to promote LTP. They have been patented in the US and are beginning clinical trials.