Prediction and prevention of prescription drug abuse Role of preclinical assessment of substance abuse liability

By Julie Marusich, Timothy Lefever, Scott Novak, Bruce Blough, Jenny Wiley

In 2011, the prevalence of prescription drug abuse exceeded that of any other illicit drug except marijuana. Consequently, efforts to curtail abuse of new medications should begin during the drug development process, where abuse liability can be identified and addressed before a candidate medication has widespread use. The first step in this process is scheduling with the Drug Enforcement Agency so that legal access is appropriately restricted, dependent upon levels of abuse risk and medical benefit. To facilitate scheduling, the Food and Drug Administration (FDA) has published guidance for industry that describes assessment of abuse liability. The purpose of this paper is to review methods that may be used to satisfy the FDA's regulatory requirements for animal behavioral and dependence pharmacology. Methods include psychomotor activity, self-administration (an animal model of the rewarding effects of a drug), drug discrimination (an animal model of the subjective effects of a drug), and evaluation of tolerance and dependence. Data from tests with known drugs of abuse illustrate typical results. While the use of preclinical data to predict abuse liability is an imperfect process, these methods have substantial predictive validity. The ultimate goal is to increase consumer safety through appropriate scheduling of new medications.


Marusich, J., Lefever, T., Novak, S., Blough, B., & Wiley, J. (2013). Prediction and prevention of prescription drug abuse: Role of preclinical assessment of substance abuse liability. (RTI Press Publication No. OP-0014-1307). Research Triangle Park, NC: RTI Press.

© 2019 RTI International. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.


Julie MarusichJulie A. Marusich, PhD, is a research pharmacologist at RTI , where she works as part of the behavioral pharmacology team, focusing on the behavioral effects of drugs of abuse.

Timothy LefeverTimothy W. Lefever, MA, manages RTI International’s Neurobehavioral Laboratory. Mr. Lefever has been conducting preclinical behavioral research for over 13 years and has been testing the effects of cannabinoids in these models extensively during the past 5 years. 

Scott NovakScott P. Novak, PhD, is a senior research public health analyst in RTI’s Behavioral Health Research Division. His current work focuses on characterizing the epidemiological trends and identifying the at-risk populations for prescription drug abuse and co-occurring illicit drug use.

Bruce BloughBruce E. Blough, PhD, is a senior research chemist in RTI’s Organic and Medicinal Chemistry group.

Jenny WileyJenny L. Wiley, PhD, is a leading expert in behavioral pharmacology. Dr. Wiley designs and supervises a program of in vivo research at RTI International, including the synthesis and development of candidate medications and investigation of neural mechanisms underlying substance abuse. She also conducts independent NIH grant-supported research in the area of cannabinoid pharmacology.

Contact RTI Press

To contact an author, request an exam or review copy, or seek permission to use copyrighted content, contact our editorial team.