Identifying appropriate subjects for abuse liability studies using prestudy pharmacological testing

Abstract

Drug abuse liability testing usually involves a subject population of individuals who are current or former drug abusers. To determine whether choosing subjects from a wider and more diverse population of nondrug abusers results in subjective response patterns that are pharmacologically associated with drug abuse liability, a series of studies were conducted using the prescription opiate hydromorphone and the barbiturate secobarbital to prescreen subjects before their acceptance into large multidrug, multidose abuse liability studies. The results of these prescreening studies show that there were some subjects who were not able to report consistently and reliably relevant drug effects, even though they received pharmacologically active doses as measured by objective indexes such as pupil diameter for the opiate study and psychomotor impairment for the barbiturate study. To test the consistency of these results, several of the subjects from the hydromorphone screening were retested with hydrocodone. The results demonstrate that subjects who were unable to report positive subjective effects of hydromorphone were also unable to respond appropriately to hydrocodone, and subjects who responded appropriately to hydromorphone in the prescreening study consistently responded to another opiate. Using this prescreening methodology has allowed sensitive and reliable data on the abuse liability of benzodiazepine agonists and partial agonists, barbiturates, carbamate compounds, amphetamines, selective serotonin reuptake inhibitors and prescription opiate compounds to be generated using a nondrug abusing population. In conclusion, due to the relative heterogeneity of a population of nondrug abusers compared with a drug abusing population, it is necessary to prescreen subjects for their ability to detect and report subjective drug effects, and to distinguish the effects of an active drug from those of placebo. Selecting subjects from this population has several advantages over selecting subjects from the drug abusing population that outweigh any inconvenience of this simple prescreening methodology.