Our bodies can’t handle large doses of refined/high density compounds (sugar, alcohol, opioids, etc) or social interactions (being judged by 1000s/millions).
Those exogenous compounds bind to endogenous receptors.
Social interactions lead to endogenous release of compounds that bind to endogenous receptors.
A human body limits how much endogenous ligands it produces.
There are different types of limits for exogenous ligands.