I tried this last year with Linux Mint, and I learned that a normal USB drive just doesn’t have the read/write speed to even e.g. operate Firefox smoothly. There are different ways to address that, none of which really did the trick for me, so the best bet is to just get a drive with the fastest read/write rate possible. I’ve heard that it can run tolerably well on one of those more performant drives, but I didn’t try it myself.