26 March 2020

A new study uncovers how stimulants like Ritalin work in the brain, and it challenges some misconceptions for its recreative use. The collaboration between Radboudumc and Brown University (USA) was published in the journal Science.

People tend to think that Ritalin and Adderall help them to focus. And they do, in some sense. But what this study shows is that they do so, in part, by increasing your cognitive motivation. Your perceived benefits of performing a demanding task are elevated, while the perceived costs are reduced. This effect is separate from any changes in actual ability.

Ritalin in the brain
Ritalin works by increasing the amount of dopamine released in the striatum, a key region in the brain related to motivation, action and cognition. Dopamine is a molecule that transports signals between nerve cells, and previous studies have shown that higher levels of dopamine make both humans and rodents more motivated to perform physically demanding tasks. The question was whether this was also the case for cognitive tasks: do the stimulants increase your ability to do something, or do they make you more motivated?

From observation to test
The study was conceptualized after the team at Radboudumc, led by professor Cognitive Neuropsychiatry Roshan Cools, theme Stress-related disorders, made an intriguing observation about the efficacy of drugs that stimulate dopamine receptors (used in Parkinson’s disease for example). It turned out that the effects of those drugs vary greatly across individuals, and that these effects can be predicted from the individuals’ baseline dopamine levels. The researchers wanted to find out if this was also true for methylphenidate, the active substance in drugs like Ritalin and Concerta that are used by so many people with ADHD, but also as smart pills by healthy people to enhance cognition and performance.

Using a model developed at Brown University, suggesting that dopamine changes the way the striatum emphasizes the benefits rather than the costs of completing physical and mental actions, Cools, from the Donders Institute for Brain, Cognition and Behaviour, set out to run an experiment. She and her team studied a group of healthy adults between 18 and 43 years of age. They measured the normal dopamine levels of each participant (using a PET-scan), and then asked them if they would take part in a series of cognitively demanding tasks. Some of these tasks were easier than others, but with varying amounts of monetary rewards, those who took on the hardest tasks stood to make the most money.

The participants participated in the experiment three times: once after taking a placebo, once after taking methylphenidate and once taking sulpiride, an antipsychotic drug that is thought to elevate dopamine levels when taken in low doses (at higher doses it is used to treat schizophrenia and major depressive disorder).

Cost versus benefit
The results of the experiment matched the mathematical model. Those with lower dopamine levels made decisions that shows they were more focused on avoiding difficult cognitive work – in other words, more sensitive to the costs of completing the work. The group with high dopamine levels, on the contrary, acted more sensitive to the differences in the amount of money they could earn – in other words, more focused on the potential benefits of completing the task. It did not matter whether the elevated dopamine levels were natural, or enhanced by the drugs.

The researchers hope their study helps future researchers and medical professionals better understand cognitive mechanisms, allowing them to identify connections between dopamine levels and disorders such as anxiety, depression, ADHD and schizophrenia.

The research was primarily funded by a Netherlands Organization for Scientific Research VICI grant, No. 453-14-005 (2015/01379/VI) to Roshan Cools.

Background: dopamine and decisions
Every person has a slightly different base level of dopamine, but high or low – no single dopamine level is inherently better than another. An active, high-dopamine person may take fulfilling, happiness-boosting risks but may also be more prone to injury; a risk-averse, low-dopamine person may avoid injuries and disappointments but may also miss out on adventures. And dopamine levels don’t necessarily stay the same from one day to the next: they may decrease in response to danger or lack of sleep, and they may increase when people feel safe and supported. 

In other words, most people can trust their natural dopamine levels to guide them toward the right decisions. Of course, previous experiments have made it clear that many people with particularly low dopamine levels — including those who are diagnosed with depression or ADHD — can benefit from dopamine-boosting stimulant medications. But those medications are never certain to improve the lives of those who are healthy and who choose to use them recreationally. Doing so could, in fact, lead some to make poorer decisions, because when you raise dopamine in someone who already has a high dopamine level, every decision seems like it has benefit, which could distract from the real beneficial tasks.


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