Human abuse liability assessment of e-cigarettes: Why, what and how?

Cigarette smoking is the world's leading cause of preventable death and disease. Alternative nicotine products such as e-cigarettes have tobacco harm reduction potential, by providing smokers with an alternative form of nicotine delivery but with either the reduced presence or absence of the numerous harmful chemicals found in combustible cigarette smoke. One aspect of importance in determining the potential of e-cigarettes to provide a viable alternative to combustible cigarettes for smokers is their ability to cause dependence, also known as their abuse liability. E-cigarettes with little or no abuse liability would be unlikely to be used as a substitute for cigarettes, whereas at least some degree of abuse liability is acknowledged as supportive both to aiding cigarette substitution or complete cessation and to preventing relapse. Given this link between abuse liability and substitution efficacy, human studies assessing the abuse liability of e-cigarettes are important to determine their true harm reduction potential. In this review, the concept of tobacco product abuse liability is discussed, along with the primary elements-pharmacokinetics and pharmacodynamics (subjective effects)-that need to be assessed to determine abuse liability. The review also presents a number of human abuse liability study design considerations and discusses what existing studies in the literature tell us about the abuse liability and harm reduction potential of e-cigarettes.