Cognitive enhancement effects of stimulants: a randomized controlled trial testing methylphenidate, modafinil, and caffeine

Abstract

Rational At all times humans have made attempts to improve their cognitive abilities by different means, among others, with the use of stimulants. Widely available stimulants such as caffeine, but also prescription substances such as methylphenidate and modafinil, are being used by healthy individuals to enhance cognitive performance. Objectives There is a lack of knowledge on the effects of prescription stimulants when taken by healthy individuals (as compared with patients) and especially on the effects of different substances across different cognitive domains. Methods We conducted a pilot study with three arms in which male participants received placebo and one of three stimulants (caffeine, methylphenidate, modafinil) and assessed cognitive performance with a test battery that captures various cognitive domains. Results Our study showed some moderate effects of the three stimulants tested. Methylphenidate had positive effects on self-reported fatigue as well as on declarative memory 24 hours after learning; caffeine had a positive effect on sustained attention; there was no significant effect of modafinil in any of the instruments of our test battery. All stimulants were well tolerated, and no trade-off negative effects on other cognitive domains were found. Conclusions The few observed significant positive effects of the tested stimulants were domain-specific and of rather low magnitude. The results can inform the use of stimulants for cognitive enhancement purposes as well as direct further research to investigate the effects of stimulants on specific cognitive domains that seem most promising, possibly by using tasks that are more demanding.

Cognitive enhancement: Effects of methylphenidate, modafinil and caffeine on latent memory and resting state functional connectivity in healthy adults

“…Specifically, dopamine has been shown to shape large-scale neural networks including prefrontal regions underlying cognitive functions. For this reason, we utilized behavioral and resting state fMRI data from a double-blind randomized placebo-controlled study (see Repantis et al, 2021) and investigated the combined effects of MPH, MOD and CAF on memory and FC at rest (Repantis et al, 2021). We hypothesized that memory performance should increase and large-scale neural networks including prefrontal regions should be modulated as a function of all three stimulants.…”

“…In the original study two different memory tasks were administered – memory of visual and audio material (see Repantis et al, 2021). For better comparability, we used the same memory outcome measures as reported in Repantis and colleagues (2021).…”

“…The copyright holder for this this version posted November 8, 2021. ; https://doi.org/10. 1101/2021 Although the cognitive enhancement effect of all three stimulants is heavily dose-dependent (Woord et al, 2014), there seems to be converging evidence that single-dose intake can improve memory function in a healthy population (for different meta-analyses, see Linssen et al, 2014;Repantis, 2010;Ilieva et al, 2015). Despite the different primary modes of action of the stimulants, this poses the question whether there is a shared cognitive enhancement effect related to memory.…”

“…In this study, 48 male participants were randomized into three groups receiving a stimulant (CAF, MOD, MPH) or a placebo first in two separate sessions. Next to fMRI data acquisition, the participants performed a series of cognitive tasks including different memory tasks (see, Methods section and Repantis et al, 2021).…”

The Neurophysiology of Caffeine as a Central Nervous System Stimulant and the Resultant Effects on Cognitive Function

“…In contrast to the previous four studies, a recent study by Repantis et al suggested improvements in cognitive parameters with caffeine use [16]. In a randomized, double-blind, placebo-controlled study, cognitive performance in 48 male participants (21-36 years old) was assessed after taking one of three stimulants (caffeine, methylphenidate (MHP), modafinil (MOD)).…”