Here's an idea smart guy...how about telling us why the Constitution will NOT be relevant.
If the FEDS can use the Supremecy clause to dictate that state's laws are improper, they, by definition, have removed the value of many of the amendments.
All they (the feds) have to do is make a law to fit their liking, and any state that doesn't fall in line is, let's say, "forced" to capitulate to the feds via supremecy.
Could be drugs, could be intra-state commerce, could be healthcare, could be anything... Frankly, I'm surprised it hasn't been used more. Does that make sense?