ABSTRACT
The purpose of this review is to illustrate the utility and value of employing human self-administration procedures in medication development, including abuse liability assessments of novel medications and evaluation of potential pharmacotherapies for substance use disorders. Traditionally, human abuse liability testing has relied primarily on subjective reports describing drug action by use of questionnaires; similarly, drug interactions between putative treatment agents and the drugs of abuse have relied on these measures. Subjective reports are highly valued because they provide qualitative and quantitative information about the characteristics of central and peripheral pharmacodynamic effects as well as safety and tolerability. However, self-administration procedures directly examine the behavior of interest-that is, drug taking. The present paper (1) reviews the most commonly used human self-administration procedures, (2) discusses the concordance of subjective reports and self-administration within the context of medications development for substance use disorders, focusing primarily on illustrative examples from development efforts with opioid and cocaine dependence, and (3) explores the utility of applying self-administration procedures to assess the abuse liability of novel compounds, including "abuse-deterrent" formulations (ADFs). The review will focus on opioid and cocaine dependence because a rich database from both clinical laboratory and clinical trial research exists for these two drug classes. The data reviewed suggest that drug-induced changes in self-administration and subjective effects are not always concordant. Therefore, assessment of self-administration in combination with subjective effects provides a more comprehensive picture that may have improved predictive validity for translating to the clinical setting.
Subject(s)
Drug Design , Drug Evaluation/methods , Drug-Related Side Effects and Adverse Reactions , Pharmaceutical Preparations/administration & dosage , Self Administration/methods , Self Administration/psychology , Substance-Related Disorders/drug therapy , Substance-Related Disorders/psychology , Choice Behavior , Cocaine-Related Disorders/drug therapy , Cocaine-Related Disorders/prevention & control , Cocaine-Related Disorders/psychology , Conditioning, Operant , Drug Interactions , Humans , Illicit Drugs/adverse effects , Illicit Drugs/pharmacology , Narcotic Antagonists/pharmacology , Opioid-Related Disorders/drug therapy , Opioid-Related Disorders/prevention & control , Opioid-Related Disorders/psychology , Reinforcement Schedule , Reinforcement, Psychology , Substance-Related Disorders/prevention & controlABSTRACT
To learn whether the percentage of time spent at different functional levels varies as a function of age, we studied 44 older (mean age 70 years) and 46 younger (mean age 27 years) urban, community-dwelling volunteers who participated in a study of normative ageing of the cardiovascular system. Each subject completed one 24-hour activity diary which was coded using a standardized scoring system for functional activity levels and energy levels. Compared with younger persons, older persons spent larger percentage of their day performing basic (BADLs) and intermediate activities of daily living (IADLs) and less time in physical advanced activities of daily living and sleeping. Older women spent more time than younger women performing BADLs and more time than younger women or older men performing IADLs. These findings support the concept of functional changes associated with healthy ageing which may be more pronounced in women. Our results may also reflect a cohort effect that may disappear with the change of traditional sex roles.
