‘Smart’ Drugs Alter Developing Brain

by Kayt Sukel

June 23, 2014

At Neuroscience 2012, Barbara Sahakian, a psychiatrist at the University of Cambridge, led a rousing discussion regarding the ethics surround the use of so-called "smart" drugs, or drugs that improve attention, memory, wakefulness and cognitive capabilities. In her talk, Sahakian highlighted that the number of young students and professionals using such drugs is only growing-and stressed the pros and cons of such use must be discussed in the context of both the individual and society at large. It was one of the most talked about speeches at the conference that year.

Certainly, cognitive enhancement, by any means, remains a controversial issue. But Julian Savulescu, the Uehiro Chair in Practical Ethics at the University of Oxford, says, on the whole, there is a lot of benefit to cognitive enhancement. He says that the ability to enhance memory and learning, even through the use of drugs, offers healthy people not only the ability to improve their academic performance but also their overall well-being and life success. And that, he argues, provides an economic benefit to society at large.

"I think there are a lot of good reasons to take 'smart' drugs. Overwhelmingly, there are a weight of reasons in favor of taking them," he says. "There are only two good objections to it that I see. One is that their use may be potentially exacerbating social injustice. But I think that's easily addressed by making sure people have basic access to them in the same way they have access to basic education. The second objection is one of safety. That they might be risky and we just don't know the long-term effects of their use. And that's a scientific question that needs to be answered."

To date, there has been a serious lack of research concerning the effects of these drugs, many of which are available without a prescription over the Internet, in healthy individuals. A recent review from researchers at the Drexel University College of Medicine suggests the use of cognitive enhancing drugs may have unintended and quite negative consequences, particularly in young brains.

What might "smart" drugs do to young brains?

When Kimberly Urban, a psychologist at the University of Delaware, was pursing her graduate work at Drexel University College of Medicine, she was struck by how little research had been done into the long-term effects of "smart" drugs like methylphenidate, better known as Ritalin. More and more reports suggest that even children are using Ritalin "off-label," or in a manner not outlined on the drug's Food and Drug Administration approved packaging label, to help improve focus and memory. And that, Urban says, raises a lot of questions regarding safety.

"As I was looking into this, I realized there were virtually no studies, really nothing at all in the literature, on how a drug like Ritalin might act on a normal, young brain," she says. "There's plenty of research to show that it's safe for healthy adults. But the younger brain is a lot more flexible-it's a lot more adaptable than the adult brain. So we decided to look at what Ritalin, a drug that profoundly affects important neurotransmitters and circuits, might do in the brains of younger children."

She and advisor Wen-Jun Gao exposed juvenile rats to low-doses of Ritalin. They soon observed key changes to the prefrontal cortex-in particular, impairments to the region's natural plasticity. In addition, the two saw that even low dosages in young rats led to problems with working memory and task-switching flexibility. These findings led Urban and Gao to look at other "smart" drugs, including modafinil, a wakefulness drug better known as Provigil, and ampakines, a new class of alertness drugs currently studied by the US Army. They found similar effects-younger brains were also more sensitive to these drugs-and showed changes to prefrontal function.

"If you take these drugs long term, you see that it stimulates the neurons, using a lot of dopamine. It modifies the way the circuits work and the neurons don't work in the same way anymore," says Gao. "And since you have those changes, the drug doesn't work as well anymore. You have to take more and more to get the same effects, you see more addiction. The young brain seems much more sensitive to these changes-and suggests that young people who take these kinds of drugs need to be very cautious and careful."

An evolving ethical question

As Savulescu said, there can be great benefit to cognitive enhancement. And even Urban and Gao won't go so far as to say that younger students should never take cognitive enhancing drugs. They emphasize that a lot more research should be done about the long-term effects before making any strong conclusions. Savulescu agrees.

"At the moment, the only way you can study these drugs is to study them as a treatment for a disease. But there are so many normal people-students, lawyers and doctors-who are taking these drugs on a regular basis. And there is no systematic study of the effects on these people," he says. "That's crazy that we haven't. Every single one of these people should be a data point. And if there are negative effects, certainly people should be aware of that."

Urban says that though her research is preliminary, she hopes it raises a cautionary flag, and makes people think carefully about the risk/benefit ratios of taking "smart" drugs.

"Introducing these kind of artificial chemicals, especially in the young brain, can change the basic chemistry of your brain. And it could be devastating in the long-term for younger people," she says. "But, ultimately, whether or not you take these kinds of drug has to be a decision that every person makes for themselves."