Drug abuse liability testing

The nonmedical use of prescription drugs has evolved toward a severe health issue worldwide. To date, prescription drugs are the second of abused substances after marijuana in teens in the United States (White House ONDCP, 2014) and include pain killers (opioids), stimulants (ADHD medication), and antidepressants. 

In addition, kinetics need to be determined in the preclinical abuse liability studies. A CNS-active drug candidate with a kinetic profile demonstrating a short half-life might be subject to potential abuse. 

With respect to animal welfare, care must be taken not to interact with the animal s comfort and health status (USDA Animal Welfare Act, 1996). 

2 Preclinical Models to Test Abuse Potential of CNS-Active Drug Candidates 

According to the regulatory requirements of drug licensing authorities, the rat is considered the preferred species to perform drug abuse liability studies (EMA, 2006 ICH, 2009 FDA, 2010). 

---

TESTING DRUGS FOR PHYSICAL DEPENDENCE POTENTIAL AND ABUSE LIABILITY. Joseph V. Brady, Ph.D., and Scott E. Lukas, Ph.D., eds. 

Brady, J.V. and Lukas, S.E., Testing Drugs for Physical Dependence Potential and Abuse Liability. NIDA Research Monograph 52, 1984. 

Holtzman, S.G., Discriminative stimulus effects of drug relationship to abuse liability, in Testing and Evaluation of Drugs of Abuse, M.W. Adler and A. Cowan, Eds., Wiley-Liss, New York, 1990. 

The principal weakness of drug discrimination procedures for assessing abuse liability is that they provide only indirect evidence regarding abuse. If a test substance is discriminated as being similar to a known drug of abuse, this is taken to indicate that the test substance is likely to be abused in a similar manner. On the other hand, if a test substance does not share discriminative stimulus effects with any known drug of abuse, drug discrimination procedures alone provide no indication of whether the test substance is likely to be abused. 

---