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This interacts with the HPA axis your body's central stress-response system in a straightforward way: when you're physically exhausted and neurologically compromised, cortisol stays elevated longer, recovery from stressful events takes more time, and the subjective experience of stress intensifies

(Chang et al., 2011) Intracellular signaling

Wessells et al

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From there, it goes straight to the liver for whats known as first-pass metabolism, where a portion of it can be broken down before it ever reaches systemic circulation