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There hasn’t been a nullification crisis over powers not delegated to the federal but reserved to the States or the people. Things like regulation of commerce within States or saying things that affect interstate commerce but which are not actually interstate commerce may be regulated. There really needs to be a LOT of that sort of nullification!
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Regulate’ as per the Commerce Clause, follows the 2nd: to make regular. Federalism has been turned on its head w/ the *intentional* misapplication and misreading of the Constitution; *KNOWING*, and easily shown, to place restrictions upon GOVT, not We the People
But, yes, there should be a LOT of State vs. Fed in this area, but govt being govt, washes its own back.
The whole purpose of the clause was to give the Congress a way to prevent the States from using their regulatory powers in ways to the detriment citizens of other States.
It wasn’t even about making rules to govern the activities of private Persons or privately held entities as they sought to engage in commerce among the several States, for those doing so would still be covered by the Laws of all the States they were conducting business in when they were doing business within them.