You can see from the racial differences in alcoholism that alcohol already killed off most of the people that can't handle it, in places that have had it for millenia. That's the case for legalizing it. The same might be true of marijuana (I don't know the history).
This hasn't happened with modern drugs that didn't penetrate society the way alcohol has. Legalizing them means accepting the eugenic removal of susceptible people and their descendents from the future human population.