Drug use that releases dopamine can lead to a pleasure-pain balance shift, causing the brain to downregulate dopamine transmission and production, resulting in a hangover, come down, or craving.

“so for example um my patient uses cannabis through the endogenous opioid system that ultimately leads to the release of dopamine and the reward pathway her pleasure pain balance tilts to the side of pleasure and then her brain says oh that was good let's do that again but remember uh the balance wants to return to the level of position so it does that by adapting to that increased dopamine by downregulating dopamine transmission and production not just at Baseline levels but below Baseline levels”