History of abuse liability testing in humans.

Clinical testing for drug abuse liability began as part of a collaborative effort to develop non-addicting substitutes for morphine. Physical dependence capacity and euphorigenic potential were identified as the potent effects of morphine leading to abuse; quantitative measures were developed for these effects. Drugs were evaluated for morphine-like effects using principles of bioassay. In recent years, the alterations in mood, feeling, thinking, and perception induced by drugs (subjective effects) are viewed as the effects leading to reinforcement of drug-taking behavior and to abuse. The same procedures and methods developed for assessing these effects with opioids have subsequently been applied to other classes of drugs. At present, human drug abuse liability testing methods exist for opioids, stimulants, sedative hypnotics, serotonin agonist and antagonists, nicotine, alcohol, and caffeine.