Quick Comparison
| Adrafinil | Caffeine | |
|---|---|---|
| Half-Life | 1 hour (adrafinil itself), but modafinil metabolite: 12-15 hours | 3-7 hours (average 5 hours, highly variable by individual) |
| Typical Dosage | Standard: 300-600 mg once in the morning. 600 mg adrafinil roughly equals 200 mg modafinil. Do not use daily for extended periods due to liver metabolism. Cycle 2-3 times per week maximum. | 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. |
| Administration | Oral (capsules, powder). Takes 45-60 minutes for effects (liver conversion time). | Oral (coffee, tea, capsules, tablets, powder). Onset: 15-45 minutes. Peak effects: 30-90 minutes. |
| Research Papers | 10 papers | 9 papers |
| Categories |
Mechanism of Action
Adrafinil
Adrafinil is a prodrug—it is pharmacologically inactive until metabolized by hepatic cytochrome P450 enzymes (primarily CYP3A4) and possibly esterases into modafinil (the active metabolite) and modafinilic acid (inactive byproduct). The conversion involves oxidation of the sulfinyl group. Once converted, adrafinil acts identically to modafinil: inhibition of the dopamine transporter (DAT), activation of orexin/hypocretin neurons in the lateral hypothalamus, increased histamine release from tuberomammillary nuclei, and elevation of norepinephrine and serotonin in cortical regions. The hepatic first-pass conversion step explains the delayed onset (45-60 minutes vs 20-30 for modafinil) and the concern about liver enzyme elevation and oxidative stress with chronic daily use.
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.
Risks & Safety
Adrafinil
Common
Headache, nausea, anxiety, insomnia, stomach discomfort.
Serious
Liver enzyme elevation with chronic daily use — periodic liver function tests recommended. Same SJS risk as modafinil (extremely rare).
Rare
Skin irritation, orofacial dyskinesia.
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.
Full Profiles
Adrafinil →
A prodrug that is metabolized in the liver to modafinil. Adrafinil provides the same wakefulness and cognitive effects as modafinil but is available without a prescription in most countries. The tradeoff is that it takes longer to kick in (45-60 minutes vs 20-30 for modafinil) and puts additional load on the liver due to first-pass metabolism.
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.