“Smart” drugs can backfire when used as cognitive enhancers, according to one study

This is a MedPage Today story.

“Smart” drugs — prescription stimulants used as cognitive enhancers by people without attention-deficit hyperactivity disorder (ADHD) — reduced performance in complex daily tasks, a small randomized double-blind study showed.

Cognitive enhancers — methylphenidate (Ritalin), dextroamphetamine (Dexedrine), or modafinil (Provigil) — have led to small decreases in accuracy and efficiency and large increases in time and effort on a complex task, Dr. Peter Bossaerts of the University of Cambridge in England and the University of Melbourne in Australia, and co-authors of Science Advances.

Because the drugs induce dopamine, the researchers expected to see increased motivation. But the strain caused by this motivation may have led to more erratic thinking when participants were faced with difficult problems, they suggested.

“We were skeptical that motivation and attention alone were enough to be good at combinatorial tasks, as opposed to tasks that are easily accomplished with reinforcement learning,” Bossaerts told MedPage Today.

“Medications impact motivation, attention, and perhaps working memory, but a combinatorial task requires tackling a problem in a systematic way,” he stressed. “You don’t solve puzzles by randomly tossing pieces in the air until they accidentally fall into place.”

The trial tested 40 people without ADHD on the problem of backpack optimization, a task that involves a virtual backpack with a set capacity. Participants selected items of different weights and values ​​to maximize the value of the backpack contents. The test is designed to model complex decision making and problem solving in everyday life.

PHOTO: Dexedrine 15mg tablets is seen here in this undated file photo.

Dexedrine 15mg tablets can be seen here in this undated file photo.

Universal History Archive/Universal Images Group via Getty Images, FILE

When participants used cognitive enhancers, their effort, defined as the decision time and number of steps required to find a solution, increased compared to the placebo. With methylphenidate, for example, participants took an average of about 50 percent longer to complete the backpack task.

Productivity, defined as the mean value achieved per move, decreased compared with placebo when participants used cognition-enhancing drugs.

Differences also emerged in subgroups. People who performed higher on the placebo tended to show a greater decrease in performance and productivity after taking any of the three cognitive enhancers.

Those in the top 25% of productivity on placebo often ended up in the bottom 25% on methylphenidate, for example.

Conversely, some below-average performers on placebos improved the quality of effort with cognitive-enhancing drugs, but spent more time on the task.

“We didn’t expect this heterogeneity among participants, something rarely mentioned in drug studies,” Bossaerts said.

The study randomized participants over four visits to a single dose of one of three drugs (30 mg of methylphenidate, 15 milligrams of dextroamphetamine, or 200 milligrams of modafinil) or placebo before they were asked to solve eight instances of the backpack task.

The four visits took place in Melbourne and were separated by at least a week from each other. Participants ranged in age from 18 to 35 years; 17 were male and 23 female.

“Because the backpack task encompasses the difficulties encountered in solving everyday problems, our paradigm could help shed light on how drugs such as methylphenidate improve the daily functioning of patients suffering from, for example, ADHD,” noted Bossaerts and co-authors. .

The backpack task may also make it easier to compare people with and without ADHD, the researchers added.

“For subclinical populations, our paradigm provides a convenient framework with which to eventually discover truly smart drugs—that is, drugs that not only increase effort but also improve the quality of effort,” they wrote.

Disclosure: This work was supported by the University of Melbourne. Bossaerts had no competing interests. A coauthor reported relationships with Takeda/Shire, Medici, Novartis, Servier, Oxford University Press, and Cambridge University Press.

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