Pure psychoactive drugs and direct routes of administration are evolutionarily novel features of our environment. They are inherently pathogenic because they bypass adaptive information processing systems and act directly on ancient brain mechanisms that control emotion and behavior. Drugs that induce positive emotions give a false signal of a fitness benefit. This signal hijacks incentive mechanisms of "liking" and "wanting," and can result in continued use of drugs that no longer bring pleasure. Drugs that block negative emotions can impair useful defenses, although there are several reasons why their use is often safe nonetheless. A deeper understanding of the evolutionary origins and functions of the emotions and their neural mechanisms is needed as a basis for decisions about the use of psychoactive drugs.