The role of human drug self-administration procedures in the development of medications

S. D. Comer, J. B. Ashworth, R. W. Foltin, C. E. Johanson, J. P. Zacny, S. L. Walsh

Research output: Contribution to journalReview articlepeer-review

124 Scopus citations

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.

Original languageEnglish
Pages (from-to)1-15
Number of pages15
JournalDrug and Alcohol Dependence
Volume96
Issue number1-2
DOIs
StatePublished - Jul 1 2008

Bibliographical note

Funding Information:
The authors would like to thank Dr. Nathaniel Katz for organizing a series of conferences at the Tufts Health Care Institute on the issue of opioid risk management, which served as the impetus for this paper. A portion of this review was presented as part of a symposium at the 2006 68th Annual Scientific Meeting of the College on Problems of Drug Dependence (SLW).We gratefully acknowledge the support of the National Institute on Drug Abuse (DA09236 and DA16759 (SDC); DA06234 (RWF); DA01678, DA019433, and DA022191 (SLW). Contributors : Drs. Comer, Ashworth and Walsh wrote the contents of this paper, and Drs. Foltin, Johanson, and Zacny provided feedback on several drafts. All authors contributed to and have approved the final manuscript.

Keywords

  • Abuse liability
  • Abuse-deterrent formulation
  • Drug self-administration
  • Human

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

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