Why does the Republican leadership support them? At the more reductionist level, I've seen it best described as a "donor riot"; rather obviously the interests of the wealthy who identify as Republican are different that the base (and this is one reason why the Emmanuel Goldsteining of the libertarian Koch brothers strikes us as bizarre, then again they've got some truly dangerous thoughts).
At a more general level, these "establishment" Republicans are, or aspire to be, members of the ruling class. We of the base obviously aren't, and I don't think many of us aspire to be.
"Offend" is a good word, we are mightily offended by all this. But there's only so much we can do short of, say, starting a 3rd party that's successful enough to either threaten the Republican party such that it adopts our positions, or replace it like it replaced the Whigs (or there's a thesis that the Democratic party will die since its war on arithmetic means it will eventually fail to keep its promises, the Republican party will replace it as the party of the state, and the 3rd party becomes the natural opposition). Short of that, we can withdraw our votes, which has a strictly limited effect in the Congress, and we can and have withheld our money, which gets us back to that donor riot.
Ah, I should note there's always been a non-conservative faction in the Republican party. Its abolitionist roots were in opposition to the conservative nature of the Whigs, remember the trusting busting and imperialism of Teddy Roosevelt, and the north-east wing in general is much less conservative. Think of Nelson Rockefeller who opposed conservative Goldwater, not so conservative Nixon, and was Ford's first VP. Or former governor of Massachusetts and "severe conservative" Mitt Romney (hint, that's the first and last time I've every heard someone use the word "severe" like that).
Figure out which of these does not belong, and you will have your answer.
What's there left to like? Legal pot and gay marriage?
pot is still very much illegal on the federal level... that's important because that's the level that handle your taxes.
The federal level matters because it supplants state law. The FBI and other federal agents can arrest anyone in any state where pot is legal statewide under federal law. You just get out of having local PD arresting you for it.
Not necessarily, as state (including) local agents can generally arrest you for violations of federal criminal law, too.
States, or local authorities within states, may deprioritize such arrests, or prohibit their officers from them entirely, for certain acts that are permitted by state but not federal law, but this is by no means guaranteed (and many local law enforcement agencies have continued to at least selectively make arrests under federal drug laws for marijuana even when the act involved was permitted under state law.)
The targeted individuals would likely be screwed. Probably the biggest risk is Colorado fighting the USA directly. Perhaps it's not interstate trade so the US can't regulate, perhaps Colorado sues for lost tax revenue.
Can a conservative republican explain why the Republican leadership is supporting this? I can't really understand why free market people would be in favor of state-granted and enforced-at-taxpayer-expense monopolies. Nor do I understand why extreme patriots would be in favor of Investor-State Dispute Systems. The latter seems like a sovereignty giveaway, to an unaccountable international body. In a way, ISDS seems like big government gone wild, but it's an unelected, unaccountable international government, which should offend small government types, too.