When the US legalized alcohol its use doubled, but alcohol abuse only went up around 15%. That is, people who will only use a substance if its legal will tend to use it responsibly. I expect that if we legalized other intoxicants they'd mostly displace alcohol, which would actually be a public health win for many currently illegal drugs. For the others, I expect that having the FDA ensuring a pure supply would be enough to make it a net good idea, even if its one with disadvantages.