title: Abuse liability studies of opioid agonist-antagonists in humans.
abstract: Prediction of the abuse liability of a drug before it reaches the market is complicated by the fact that there are many factors that influence the actual abuse of a drug. Laboratory methods used in humans to assess the abuse liability of the opioids are reviewed and illustrative studies of morphine and the agonist-antagonist opioids, pentazocine, butorphanol, nalbuphine and buprenorphine, are presented. Three assessment methods, subjective effect measurement, self-administration and drug discrimination, provide information relevant to measuring reinforcing efficacy, a major determinant of the degree to which a drug is sought and self-administered by abusers. Physical dependence capacity, which can contribute to sustained drug use, is evaluated in direct addiction and substitution/suppression studies. Withdrawal precipitation studies measure antagonist activity which might limit abuse. The results of testing the agonist-antagonist opioids are generally consistent across these various methods and consistent with historical experience with these drugs, suggesting that these methods are useful in predicting abuse liability of novel opioids.
authors.affiliation: Department of Psychiatry, Francis Scott Key Medical Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21224.
authors.forename: K L
authors.initials: KL
authors.lastname: Preston
authors.forename: D R
authors.initials: DR
authors.lastname: Jasinski
mesh_terms: D001143:Arousal / Q000187:drug effects; D006801:Humans; D013287:Illicit Drugs / Q000009:adverse effects; D009292:Narcotic Antagonists / Q000009:adverse effects; D009294:Narcotics / Q000009:adverse effects; D012646:Self Administration / Q000523:psychology; D013375:Substance Withdrawal Syndrome / Q000209:etiology / Q000523:psychology; D019966:Substance-Related Disorders / Q000209:etiology* / Q000523:psychology
chemical_list: D013287:Illicit Drugs; D009292:Narcotic Antagonists; D009294:Narcotics