Prediction of Drug Abuse Liability from Animal Studies

Abstract

In this chapter, the pharmacological factors involved in predicting the abuse liability of drugs are discussed with major emphasis on their psychological dependence potential. For prediction of drug abuse liability, it is important to find and compare the drug’s effects against those of prototypic drugs. The important pharmacological properties include the following: central nervous system (CNS) effects, including operant behavioral effects; tolerance; physical dependence potential; and psychological dependence potential. It is also important to consider such chemical and pharmacokinetic properties as water solubility and speeds of absorption and elimination. In particular, psychological dependence potential is most relevant to abuse liability. To evaluate psychological dependence potential from animal studies, the reinforcing and discriminative stimulus properties of drugs must be assessed in comparison with those of prototypic drugs. When human data are available, it is important to verify the animal results on such points as pharmacokinetics and CNS drug susceptibility which may differ across species.

Special consideration should also be given to the following in evaluating psychological dependence potential from animal studies: differences in reinforcing effects depending on the experimental procedure used, analysis of reinforcement data obtained in intragastric self-administration, daily dose and CNS manifestation in self-administration experiments, and influence of physical dependence. From a practical viewpoint, it is also important to predict the nature and extent of ill effects which arise as a consequence of abuse. For this, such drug properties as the CNS effects, psychological dependence potential, toxicity, tolerance, and physical dependence potential must be considered.