Something i always do before i try a new drug is extensively research it. Read trip reports, the good and the bad. Find out how it effects your body, and what complications may arise. Know medications it may clash with.

In effect, before you try a new drug, know exactly what is going to be happening. It should strip away the paranoia, aside from that, it just takes a strong mind to remind yourself that it's all in the head.

That and a trip sitter, even if it's just shrooms, it was your first time.