EXPECTANCY AS A MEDIATOR OF DRUG AND PLACEBO EFFECTS: METHODOLOGICAL AND CLINICAL CONSIDERATIONS FOR HUMAN RESEARCH OF NICOTINE AND TOBACCO EFFECTS

Abstract

Drug responses are frequently presumed to arise directly from the pharmacological properties of ingested substances; however, there is growing recognition that non-pharmacological factors likely also make important contributions. Despite this, limited research has assessed the independent and interactive contributions of pharmacological and non-pharmacological factors to drug responses. The present dissertation aimed to assess the relative contribution of pharmacological and non-pharmacological factors to drug responses using nicotine and tobacco as a model. This dissertation included four studies which used the balanced placebo design, a factorial design that allows for the assessment of the independent and combined impact of drug pharmacology and drug expectation (i.e. the belief that an active drug has been consumed; a non-pharmacological factor) on drug responses. This was achieved by crossing actual drug assignment (given active drug vs. inert placebo) with instructions regarding drug assignment (told active drug vs. inert placebo). Findings from the four studies suggest that expectancy makes a substantial contribution to the acute effects of nicotine replacement therapy (NRT) and tobacco administration on subjective craving. A number of additional non-pharmacological factors also impacted craving and cigarette self-administration following NRT and tobacco use. Taken together, these findings highlight that non-pharmacological factors make an important contribution to subjective and behavioural drug responses. Targeting non-pharmacological factors in interventions may therefore be effective in improving treatment outcomes, particularly within the context of smoking cessation.