Modafinil

Modafinil is a racemic, non-amphetamine wakefulness drug. Its R-enantiomer is sold as armodafinil, and its prodrug as adrafinil [1]. It is licensed for excessive daytime sleepiness in narcolepsy, obstructive sleep apnoea and shift work sleep disorder [1].

Its reputation as a cognitive enhancer is bigger than the evidence. A 2015 systematic review found it enhances attention, executive function, and learning and memory in healthy, non-sleep-deprived people, especially on longer and more complex tasks [3]. A later set of meta-analyses put the overall effect at a small SMD of 0.12, driven by memory updating. Methylphenidate had a larger effect in the same analysis [2].

The mechanism is still debated. PET imaging shows modafinil binds the dopamine transporter in humans, the same target as cocaine, though with a very different profile [4]. It raises cortical catecholamines directly and indirectly increases serotonin, glutamate, orexin and histamine while decreasing GABA [3].

Modafinil is a prescription drug and should be treated like one. It induces CYP3A4/5, mainly in the gut. In a controlled study it markedly lowered triazolam levels and modestly lowered ethinyl estradiol, the oestrogen in many contraceptive pills [5]. The review literature also covers dependence and misuse potential and its forensic relevance [1].

The best-documented interaction is enzyme induction. Drugs that undergo heavy first-pass CYP3A4 metabolism in the gut are the most affected [5]. That includes some hormonal contraceptives, where reduced effectiveness is the practical concern.