Messing with our minds

Want to improve your mental ability, boost concentration and even neutralise painful memories? There's a new generation of drugs to help you, says Jeremy Laurance

To err is human. But for the pilot of a commercial airliner, it is unacceptable. As holidaymakers jet off on winter breaks or plan next summer's long-haul adventure, the one thing that they will demand above all is safety. Airlines have spent millions devising elaborate systems to guarantee maximum safety. Pilot error can never be ruled out, but researchers now believe that it might be reduced - by careful tweaking of brain chemistry. Drugs are becoming available that increase alertness and improve concentration. Should all pilots take them?

This question has begun to tax scientists in the US involved in the development of so-called "smart" drugs - chemical enhancements for the mind. A range of compounds are being tested - some are already available and being traded over the internet - that may change not only the way we perform, but what we think of as "normal" performance.

The drugs being examined have applications far beyond air travel. Three areas that are attracting attention are movement and endurance, attention and learning, and moods. Medicines such as anabolic steroids can already make people stronger, swifter and more enduring. Though life-giving to victims of muscle disorders, they are widely abused in sport. Long- distance lorry drivers and Air Force pilots have used amphetamines to ward off drowsiness. Generations of students have sustained themselves through exams with over-the-counter caffeine tablets. But the new "cognitive enhancers" may offer more powerful, better targeted and longer lasting improvements in mental acuity. And some are already being tested on human volunteers.

One such drug is donepezil, a cholinesterase inhibitor developed for the treatment of dementia. This drug slows the progress of Alzheimer's disease and is being used as a treatment for age-associated memory impairment. But what is causing excitement among researchers is the possibility that donepezil may boost highly skilled performance, where concentration and alertness are prerequisites. A study published in the journal Neurology found that commercial pilots who took 5mg of donepezil for one month performed better than pilots on a placebo when asked to fly a Cessna 172 on a flight simulator. There was a marked difference between the groups when dealing with emergencies.

Modafinil, a drug used to treat the sleep disorder narcolepsy, has also been tested on pilots. A trial reported in the Psychopharmacology journal found that it boosted the performance of helicopter pilots flying on simulators who had been deprived of sleep.

Anyone who has gone two nights without sleep will know what it is like to suffer from extreme tiredness. Nothing can defeat the desire to sleep. Nothing except, apparently, modafinil. While commercial pilots have strict rules governing flying time and rest periods, fighter pilots may be called to action at a moment's notice. Modafinil is under investigation by the military for its ability to keep pilots and other members of the armed forces awake for long periods without the "rebound" effect associated with stimulants such as amphetamines.

Barbara Sahakian, Professor of Neuropsychology at the University of Cambridge, who tested modafinil in a series of experiments on volunteers found that they showed greater concentration, faster learning and increased mental agility. "It may be the first real smart drug," she says. "A lot of people will probably take modafinil. I suspect they do already."

"If people can gain a millimetre, they'll want to take it," says Jerome Yesavage, director of Stanford University's Ageing Clinical Research Center, and an author of the donepezil study. That view was backed by Judy Illes, a psychologist at Stanford's Centre for Biomedical Ethics. Mind-enhancing medicine could become as "ordinary as a cup of coffee", she says.

If drugs such as donepezil and modafinil were proved to raise performance, and hence safety, the implications could be far-reaching. Airline executives might require pilots to take the drugs, or offer financial incentives for doing so. They might market their airline as the one whose pilots took the safety-enhancing drug. Would people pay more to fly on such an airline?

The question is raised in a review of the new science, dubbed "cosmetic neurology", by Dr Anjan Chatterjee, a neurologist at the University of Pennsylvania. As the rich turn to cosmetic surgery to refine what nature gave them, cosmetic neurology offers a different kind of personal improvement. It is the "nip and tuck" for the mind. The conventional aids of caffeine, alcohol and tobacco are already used to boost mood and performance, and neurologists argue that the use of other drugs is a logical extension of this self-medication. Writing in Annals of Neurology, Dr Chatterjee says that amphetamine drugs that help stroke patients who have suffered partial paralysis to relearn motor skills might assist healthy individuals to learn to swim or play the piano. A new class of drugs called ampakines are being investigated as memory enhancers, and have already been shown to boost recall in early studies in humans.

Trials of the heart drug propranolol, a beta-blocker, have shown that it can neutralise emotionally charged memories so that they do not cause distress when recalled. In one experiment, reported in Biological Psychiatry, patients injured in accidents were given propranolol in the A&E department and were found to suffer fewer post-traumatic stress disorder symptoms when assessed one month later.

The new science is creating problems for neurologists, who are used to treating the sick, not enhancing the healthy. Dr Chatterjee writes: "One plausible scenario is that neurologists will become quality-of-life consultants. Following the model of financial consultants, we could offer a menu of options with the likely outcomes and risks." The advent of cosmetic neurology is inevitable, he says, and warns: "Prospecting for better brains may be the new gold rush."

Signs that it has already arrived can be seen on college campuses in the US. Faced with the pressure of exams and essay deadlines, students have been abandoning the traditional crutches of coffee and cigarettes for Ritalin, a stimulant best known as a treatment for hyperactive children. It has found a ready black market among students who are desperate to succeed. Users say that it helps them to concentrate.

Anecdotal reports from drug agencies in Britain suggest that the problem is just emerging here. It has already spread to Canada and Australia, and university authorities have been warned to be vigilant. The search for a short cut in learning has worried teachers. But doctors have confirmed the potential benefits of the drugs, unwittingly encouraging the trend. For example, Eric Heiligenstein, the director of clinical psychiatry at Wisconsin University, says: "Caffeine is fine. This [Ritalin] is better. Students are able to accumulate more information in a shorter time. They minimise fatigue and help maintain a high performance level." A study of 2,200 students at an unnamed university in North America, published in Pharmacotherapy last year, found that 66 of them (3 per cent) admitted abusing Ritalin in the previous year. "Illicit use of prescription-only stimulants on college campuses is a potentially serious public health issue," it said.

If "natural" performance or responses can be boosted in these areas, it may challenge our concept of what it is to be human. In one view, medicine should be about healing the sick, not turning people into gods. But the boundary between therapy and enhancement can be hard to define. Short people can be treated with growth hormone - but is that cosmetic or therapeutic? In an ageing society, treatments to boost attention, learning and memory will be increasingly relevant - but should they be applied to people who are healthy but merely old?

In the field of athletics, drug use is rife but it is referred to disparagingly as "doping". The underlying assumption is that boosting performance without doing the work is cheating and undermines human endeavour. Yet no one feels the same way about putting up with a headache or indigestion. We reach for tablets without hesitation. The ethical dilemma may prove to be academic, however, if the drugs now being tested fail to deliver on performance, or their side-effects prove to be troublesome.

A memory drug might cause subjects to remember too much detail, cluttering the mind, for example. Martha Farah, a psychologist at the University of Pennsylvania, says: "The brain was designed by evolution over millennia to be well adapted because of the lives we lead. We are better served by being able to focus on the essential information than being able to remember every little detail. We meddle with these designs at our peril."

CX-516
Ampakines
Urine tests?
Rasagiline.com
Smarter brains?
New smart drugs
Donepezil (Aricept)
Cosmetic neurology?
Methylphenidate (Ritalin)
The race to save memories
New smart drugs/nootropics
Smart drugs and aging brains
Smart drugs and mind control
Scepticism about smart drugs
Mood and cognitive performance
Modafinil (Provigil, Alertec, Vigicer)
Alzheimer's Disease: resources and hotlinks

Refs
SMART DRUGS 2: REVIEW