What also doesn’t make sense is that we needed to pass a Constitutional Amendment to nationally prohibit a substance (which we repealed); and we now have national/federal regulation “intoxicating or mind-altering substances” and firearms via things like the BATFE and the DEA. I have yet to hear a good explanation [Constitutionally-based] of these agencies existence.
That's because there is no good Constitutionally based justification for them. They are all contingent on very fast and loose interpretations of the interstate commerce clause.
Not necessarilly a good explanation, but probably the real one: Back in 1919(?) when Prohibition was passed, the courts respected the Constitution enough to give legislators pause. By 1936, with the way Roosevelt was packing the Supreme Court, such a formality as an amendment to the Constitution was no longer considered necessary.