Smart drugs fall short of cognitive enhancers

Recently, there has been an increase in the use of prescription stimulant drugs by students and employees to increase their academic and work productivity. While these drugs have been perceived to improve an individual’s cognitive function, the available evidence is inconclusive. Typically, improvements in cognition were seen only in the clinical population rather than the general public. Interestingly, even in the clinical population, improvements in cognitive deficits were marginal. Therefore, it is necessary to evaluate the effectiveness of these drugs in real conditions.

Study: Aren't you that smart?  Smart drugs increase the level but decrease the quality of cognitive effort.  Image Credit: Victor Moussa / ShutterstockStudy: Aren’t you that smart? Smart drugs increase the level but decrease the quality of cognitive effort. Image Credit: Victor Moussa / Shutterstock


Many everyday tasks can fall into the math class of “hard” problems. Typically, these problems belong to the hard non-deterministic polynomial (NP) complexity class. These tasks require systematic approaches (algorithms) to achieve optimal results. In the case of significant complex problems (for example, the number of ways to repair a product or the number of stops to make on a delivery trip), multiple calculations are required, quickly exceeding cognitive abilities.

A recent The progress of science study investigated the effectiveness of three popular smart drugs, namely modafinil (MOD), methylphenidate (MPH), and dextroamphetamine (DEX), compared to the difficulty of real-life daily activities, i.e. the 0-1 backpack optimization problem (” knapsack task”). A knapsack task is basically a combinatorial optimization task, the class of NP-time challenging problems.

MPH and DEX are catecholaminergic agonists associated with potentiation of dopaminergic activity in cortical and subcortical areas. They also exhibit norepinephrine activity. However, MPH is a dopamine and norepinephrine transporter inhibitor.

About the study

A total of 40 healthy individuals were recruited for the single-dose, double-blind, placebo-controlled (PLC) study. This cohort included seventeen males and twenty-three females between 18 and 35 years of age. All participants underwent semi-structured interviews and exams prior to enrollment. Those volunteers with a history of heart disease, under psychotropic medication, neurological (eg epilepsy) or psychiatric disease, and pregnancy were excluded from the cohort.

Participants were required to participate in four testing sessions, and each session had a minimum gap of seven days. At each session, participants received one of 200 mg of MOD, 30 mg of MPH, 15 mg of DEX or PLC.

Here, participants were randomly assigned into four groups. Following a counterbalanced Latin square design, each group was given a different sequence of drugs and PLCs during the sessions. During the backpack activity, each participant was presented with different objects, associated with weight and value.

Participants were presented with eight unique instances of the backpack activity via a user interface. Some cases were less taxing on working memory and arithmetic, while others were purely numerical (more complex). Participants attempted each instance twice. A time limit of four minutes was assigned for each response. To analyze the compatibility of the study results with previous experiments, participants were asked to complete four tasks of the CANTAB cognitive battery.

Study results

Even if the pharmacological treatment did not lead to a significant decrease in the possibility of obtaining a solution to the cases of the backpack problem, it positively caused a significant overall reduction in the value achieved. Time spent or levels of effort improved on average significantly in participants on smart drugs. However, heterogeneity was observed in the quality of effort tied to each drug versus PLC. Quality of effort was described as improvements in backpack value per move.

Interestingly, if an individual on PLC showed a significant increase in backpack value per move, that same person tended to be below average on smart drugs. Similarly, for an individual who performed below average under PLC, the quality of effort was above average under smart drugs. This reversal in effort quality may be because participants were more erratic in their choices on smart drugs.

All tasks were computationally demanding and the answers required systems thinking. The tasks were designed in such a way that random exploration was not effective. Good effort allocation is the key requirement for the backpacking business. Smart drugs increase subjective reward and, in parallel, reduce perceived effort. These drugs have a negative impact on efficacy.

All three smart drugs reduced participants’ performance on some of the CANTAB tasks included in this study. This study was unable to determine the effects of individual drugs in knapsack activity based on CANTAB activity values.


The current study has provided insights into how smart drugs affect the daily functioning of patients who suffer from them attention deficit hyperactivity disorder (ADHD). It has been found that smart drugs only improve motivation to work, but not the quality of effort.

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