Abuse liability assessments

Ator NA, Griffiths RR Principles of drug abuse liability assessment in laboratory animals. Drug Alcohol Depend 70(suppl) 55—72, 2003... 

Schneider NG, Jarvik ME, Forsythe AB (1984) Nicotine vs, placebo gum in the alleviation of withdrawal during smoking cessation. Addict Behav 9 149-156 Schuh KJ, Schuh LM, Henningfield JE, Stitzer ML (1997) Nicotine nasal spray and vapor inhaler abuse liability assessment. Psychopharmacology 130 352-361 Schuster CR, Henningfield J (2003) Conference on abuse liability assessment of CNS drugs. Drug Alcohol Depend 70 S1-S4... 

It is appropriate to recognize that some medications are more susceptible to abuse than others. If two medications are equally effective for a given indication, the one with lower abuse liability would obviously be preferred. Information on abuse liability is necessary for the appropriate regulation of medications and provides a basis for education of physicians, patients, and the public. In this chapter we describe the control of marketed medications, abuse-liability assessment procedures for premarketing testing in laboratory animals and humans, considerations of the formulation properties, and postmarketing surveillance of abuse. Finally, we provide three case studies of marketed medications that have been abused. 

Self-administration is predominantly used in the animal laboratory, although our review of the literature suggests that an increasing number of self-administration studies are being conducted with human volunteers. As more of the parameters are worked out, it is likely that human selfadministration studies will gain even wider use in abuse-liability assessment. 

Because faster onset of action is associated with higher potential for abuse, abuse-liability assessment should include consideration of whether a formulation can be altered to increase the speed of onset. There are numerous examples of abuse of a medication by a route other than that intended by the manufacturer. The sustained-release oral form of oxycodone, designed to deliver an initial rapid dose followed by slow release, has been widely abused by chewing the tablet, thus releasing the entire content of the tablet at once.65 There is also evidence for intravenous use of sublingual buprenorphine tablets.66 Transdermal systems developed to deliver medication slowly for extended periods of time have been prime targets for misuse,67 as discussed below in the case study of fentanyl. 

To avoid redundancy with several recently published reviews, we have limited our discussion of techniques for abuse-liability assessment. Interested readers are referred to these reviews,73,74,116-118 which appear in a special issue of the journal Drug and Alcohol Dependence. 

Jasinski, D., Johnson, R., and Henningfield, J., Abuse liability assessment in human subjects, Trends Pharmacol. Sci., 5, 196, 1984. 

Griffiths, R.R., Bigelow, G.E., and Ator, N.A., Principles of initial experimental drug abuse liability assessment in humans, Drug Alcohol Depend., 70, S41, 2003. 

Bigelow GE (1991) Draft Guidelines for Abuse Liability Assessment. Drug Abuse Advisory Committee, FDA, US Public Health Service... 

Woods JH, France CP, Winger G, Bertamio AJ, Schwarz-Stevens K (1993) Opioid abuse liability assessment in rhesus monkeys. In Herz A, Akil H, Simon EJ (eds) Handbook of Experimental Pharmacology, Vol 104/ Opioids II, chapter 55. Springer Berlin Heidelberg New York, pp 609-632 Yoshimura K, Horiuchi M, Konishi M, Yamamoto KI (1993) Physical dependence on morphine induced in dogs via the use of miniosmotic pumps. J Pharm Toxicol Meth 30 85-95... 

Conclusion To date no in vitro models are available to study the physical dependence potential and the rewarding and reinforcing properties of novel CNS-active drug candidates in development. The preclinical abuse liability assessment represents the integrated data of in vivo animal studies to predict the abuse potential of CNS-active drug candidates. 

Tompkins DA, Lanier RK, Harrison JA, Strain EC, Bigelow GE. Human abuse liability assessment of oxycodone combined with ultra-low-dose naltrexone. Psychopharmacology 2010 210 471-80. 

In the last 15 years, there has been a renewed interest by the pharmaceutical industry for the conduct of preclinical abuse liability assessments. The timeline of regulatory events from the Food and Dmg Administration (FDA) and European Medicines Agency (EMA) has motivated the increased industry interests (see Fig. 1 for an illustration of the relationship between significant events affecting the... 

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