CAR: ~15 → ~23 nmol/L salivary cortisol within 30 min of waking, in ~77% of healthy adults.
Wüst et al. (2000); Clow et al. (2004)
Caffeine half-life: 2.5–4.5 h. Peak plasma 15–120 min post-ingestion. Blocks up to 50% of cerebral A₁ receptors at typical doses.
Circulation (2000); Bauer et al. (2012) — PET, n=15
Adenosine roughly doubles over 12–16h of wakefulness. Caffeine blocks A₁/A₂A receptors competitively — adenosine keeps accumulating, causing rebound on clearance.
Reichert et al. (2022); Porkka-Heiskanen et al. (1997)
Coffee elevates cortisol ~50% above baseline. 300 mg/day × 5 days = incomplete tolerance. 250 mg × 3 doses elevated cortisol across the full day (p < .00001).
Lovallo et al. (2005, 2006) — n=96, double-blind crossover
400 mg caffeine 12h before bedtime: significant sleep onset delay. 4h before bedtime: >20 min less total sleep, >5% reduced sleep efficiency.
Sleep (2025) — randomised clinical crossover