Quick Comparison
| Caffeine | Modafinil | |
|---|---|---|
| Half-Life | 3-7 hours (average 5 hours, highly variable by individual) | 12-15 hours |
| Typical Dosage | Standard nootropic dose: 50-200 mg. With L-Theanine: 100 mg caffeine + 200 mg L-Theanine. FDA safe limit: up to 400 mg daily for healthy adults. Avoid after 2pm to protect sleep. | Standard: 100-200 mg once in the morning. For shift work: 200 mg 1 hour before the shift. Start with 100 mg to assess sensitivity. Do not take after noon due to the very long half-life. |
| Administration | Oral (coffee, tea, capsules, tablets, powder). Onset: 15-45 minutes. Peak effects: 30-90 minutes. | Oral (tablets). Well-absorbed with or without food, though food delays peak effects slightly. |
| Research Papers | 9 papers | 8 papers |
| Categories |
Mechanism of Action
Caffeine
Caffeine is a non-selective adenosine receptor antagonist with highest affinity for A1 and A2A subtypes. Adenosine accumulates during wakefulness and promotes sleepiness by binding to A1 receptors (inhibiting adenylyl cyclase and reducing neuronal excitability) and A2A receptors (modulating dopamine D2 receptor signaling in striatum). Caffeine competitively blocks these receptors, preventing the drowsiness signal. This disinhibition indirectly increases dopamine, norepinephrine, and acetylcholine neurotransmission via downstream pathways. Caffeine also inhibits phosphodiesterase (PDE) enzymes—particularly PDE4 in the brain—reducing cAMP degradation. Elevated intracellular cAMP amplifies catecholamine signaling through PKA-mediated phosphorylation of CREB and other transcription factors, enhancing alertness and cognitive performance.
Modafinil
Modafinil's exact mechanism is not fully understood but involves multiple neurotransmitter systems. It inhibits the dopamine transporter (DAT) with moderate affinity, weakly increasing synaptic dopamine levels without causing vesicular depletion. Modafinil activates orexin/hypocretin neurons in the lateral hypothalamus—the brain's master wakefulness system—which project to histaminergic tuberomammillary nuclei, noradrenergic locus coeruleus, and cholinergic basal forebrain. This increases histamine release (promoting cortical arousal via H1 receptors), elevates norepinephrine in the prefrontal cortex (enhancing attention and executive function), and modulates serotonin (5-HT) transmission. Unlike amphetamines, it does not cause significant vesicular catecholamine release or reverse monoamine transporters, which explains its lower abuse potential and lack of typical stimulant crash.
Risks & Safety
Caffeine
Common
Anxiety, jitteriness, insomnia, increased heart rate, digestive issues, dependency and withdrawal headaches.
Serious
Cardiac arrhythmia at very high doses (>1200 mg). Dangerous at 5-10 g.
Rare
Panic attacks, rhabdomyolysis with extreme doses.
Modafinil
Common
Headache, nausea, anxiety, insomnia, dry mouth, decreased appetite.
Serious
Stevens-Johnson syndrome (extremely rare but potentially fatal skin reaction — discontinue immediately if rash develops). May reduce effectiveness of hormonal contraceptives.
Rare
Chest pain, palpitations, psychotic episodes at very high doses.
Full Profiles
Caffeine →
The world's most widely consumed psychoactive substance. Caffeine blocks adenosine receptors in the brain, preventing the drowsiness signal and increasing alertness, focus, and reaction time. When combined with L-Theanine, it produces one of the most reliable and well-studied nootropic stacks available. Most adults consume 200-400 mg daily through coffee, tea, and other beverages.
Modafinil →
A prescription wakefulness-promoting agent (eugeroic) that is widely used off-label as a cognitive enhancer. Modafinil provides 10-15 hours of sustained focus, alertness, and motivation without the jitteriness or crash of traditional stimulants. It is the most popular pharmaceutical nootropic among students, professionals, and shift workers. Schedule IV controlled substance in the US.