This is pretty brief. The case for general drug legalization appears fairly strong.
First, there's the obvious philosophical foundation of libertarianism: if people want to do something an it doesn't harm others, they should be allowed to. However, this argument is fairly naive, because it ignores the externalities drug use has on society and ignores flaws in human psychology.
Fortunately, it doesn't look we have to muck about in weighing pros and cons. When Colorado legalized marijuana, they saw a significant fall in usage relative to the rest of the nation "title": "Following marijuana legalization, teen drug use is down in Colorado":
This seems to support the hypothesis that "rebellion" is a chief cause of marijuana use, so the natural counter-argument is that legalizing marijuana simply shifts how people rebel - from smoking pot to poping opiods. However, this appears to not be the case, as the legalization of recreational marijuana in Colorado is associated with a significant decrease in opioid-related deaths "author1": "Melvin D Livingston". The paper is behind a paywall and my college alumni account is locked, but I'll get around to reading it eventually. In the meantime, here is a chart from The Washington Post:
Though, government officials say this data is preliminary "newspaper": "The Denver Post", this evidence does put the burden of proof soundly onto proponents of this "rebellion" argument.
Likewise, when Portugal decriminalized all drugs, they saw an even more dramatic fall in drug use "title": "War on Drugs: Portugal may be winning the battle against drug abuse through decriminalisation":
Today, the Health Ministry estimates that only about 25,000 Portuguese use heroin, down from 100,000 when the policy began.
The number of Portuguese dying from overdoses plunged more than 85 per cent, before rising a bit in the aftermath of the European economic crisis of recent years. Even so, Portugal’s drug mortality rate is the lowest in Western Europe – one-tenth the rate of Britain or Denmark – and about one-fiftieth of the latest number in the US.
So, it looks like drug legalization makes sense regardless of how terrible drug use is.