Caffeine is the most widely used psychoactive compound and one of the most studied cognitive enhancers. Its strongest effects are typically on alertness, vigilance, and fatigue resistance, particularly under sleep loss or habitual low arousal. In healthy, well-rested individuals, benefits are often modest and may depend on baseline sleepiness, habitual use, and task type.

Amphetamine and methylphenidate can improve attention and task persistence, especially when baseline performance is suboptimal or when effort costs are high. However, enhancement in healthy adults often involves trade-offs: improved response speed may come with increased impulsivity, reduced flexibility, or elevated cardiovascular and psychiatric risk. Because of abuse potential, these agents raise both scientific and ethical concerns.

Wake-promoting agents such as modafinil are often positioned as more selective than classical stimulants. Evidence suggests benefits for sustained attention, fatigue resilience, and some aspects of executive function, especially in sleep deprivation or demanding conditions. Yet effect sizes are not uniformly large, and the mechanism likely involves multiple neurotransmitter systems rather than a single target.