The Role of Expectancies in Drug Withdrawal: An Experimental Analysis Using Caffeine A thesis submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Faculty of Science Llewellyn Willem Mills School of Psychology Faculty of Science University of Sydney All studies in this thesis were approved by the University of Sydney Human Research Ethics Committee Abstract This thesis reports a number of experiments whose aim was to understand the role of placebo-type effects during withdrawal from a drug. The long-term goal of this research was that of developing interventions for treating addiction that have clinical utility. The review in Chapter 1 of previous research on this topic concluded that there was sufficient evidence to suggest that withdrawal symptoms can be manipulated independently of the pharmacological effects of abstinence via verbal instructions concerning either (i) the likelihood of experiencing withdrawal symptoms, or (ii) how much of a certain drug has been consumed. Chapters 2 and 3 report two experiments designed to test the relative ability of these two forms of verbal instruction to affect symptoms produced by caffeine withdrawal. Verbal instructions concerning the likelihood of experiencing withdrawal symptoms appeared to have no effect on such symptoms. In contrast, verbal instructions concerning whether or not caffeine had been ingested had a marked effect on caffeine withdrawal. This suggests that interventions that target beliefs about dose are more effective at reducing withdrawal symptoms than interventions that attempt to influence existing expectancies about the consequences of abstinence. Chapter 4 reports an experiment that tested whether placebo caffeine withdrawal relief could occur in the absence of conscious expectancies. A group who were given decaffeinated coffee and who were instructed it was decaffeinated reported a significantly greater reduction in withdrawal symptoms than a group who were given water and told it was water, despite endorsing beliefs that decaffeinated coffee would not reduce symptoms produced by withdrawal from caffeine. This suggests that exposure to contextual cues surrounding caffeine use could elicit a withdrawal reduction effect even when this effect was not consciously expected. Chapters 5 and 6 investigated whether knowing about the timing and magnitude of dose reductions during a dose taper procedure leads to increased withdrawal symptoms. Caffeine was reduced at an identical rate over five days across three different sets of dosing instructions. One group was given accurate information, another was misinformed that their dose was remaining stable on three days and dropping to zero on the final day, and a third was given no information about dose. Knowing the caffeine dose was being reduced was associated with: (i) greater withdrawal symptoms than misinformation on the two final days, and (ii) a greater rate of increase in withdrawal across the test days than both misinformation and no information. These results support the hypothesis that being aware of the timing and magnitude of dose reductions during a dose taper can lead participants to expect an increase in withdrawal symptoms and that such expectancies can exacerbate withdrawal symptoms. Overall, the results reported in this thesis indicate that beliefs concerning how much of a drug is in the body can influence withdrawal symptoms independently of pharmacological factors. Treatments of drug addiction that reduce the negative impact of such placebo-type processes may improve clinical outcomes. “The literature on methadone maintenance suggests…that we have not developed clinical methods for controlling the effect of expectation – an effect almost universally acknowledged to be important but not as yet established by rigorous observation.” Senay, Dorus, Goldberg, & Thornton, 1977 “To sum up, I am suggesting that many of the reinforcing consequences and antecedents of drug addiction have no direct pharmacological basis. For a given individual the temporal pattern of drug use may be maintained almost entirely by secondary reinforcers.“ Vaillant, 1988 Table of Contents Abstract ......................................................................................................................... 2 Table of Contents ......................................................................................................... 5 Statement of Contribution .......................................................................................... 8 Acknowledgements ...................................................................................................... 9 Author’s Note ............................................................................................................. 10 List of Tables .............................................................................................................. 11 List of Figures ............................................................................................................. 12 List of Appendices ...................................................................................................... 14 Chapter 1: The placebo effect and placebo withdrawal ......................................... 15 1.1 Theories of the Placebo Effect ................................................................................... 15 1.1.1. Definition of Expectancies ................................................................................... 15 1.1.2 What is the Placebo Effect? ................................................................................. 16 1.1.3 Theories of the Placebo Effect .............................................................................. 19 1.2 Drug Withdrawal and Expectancy........................................................................... 26 1.2.1 Expectancies and Addiction .................................................................................. 29 1.2.2 Drug Withdrawal and its Role in Addiction .......................................................... 31 1.2.3 Evidence for Placebo Withdrawal ......................................................................... 33 1.2.4 Summary .............................................................................................................. 45 1.3 Aims and Hypotheses ................................................................................................. 46 1.3.1. Using Caffeine to Model Addiction ..................................................................... 47 1.4 References ............................................................................................................... 49 Chapter 2: The Role of Withdrawal Information and Expectancies of Consumption in Caffeine Withdrawal (Study 1) .................................................... 58 2.1 Introduction.............................................................................................................. 58 2.2 Method ..................................................................................................................... 60 2.3 Results ..................................................................................................................... 66 2.4 Discussion ................................................................................................................ 72 2.5 References ............................................................................................................... 75 Chapter 3: The Effect of Genetic Information and Information About Caffeine Content on Caffeine Withdrawal Symptoms (Study 2) .......................................... 77 3.1 Introduction.............................................................................................................. 77 3.2 Methods ................................................................................................................... 80 3.3 Results ..................................................................................................................... 86 3.4 Discussion ................................................................................................................ 93 3.5 References ............................................................................................................... 97 Chapter 4: Conscious and Unconscious Expectancies in Caffeine Withdrawal (Study 3) ...................................................................................................................... 99 4.1 Introduction.............................................................................................................. 99 4.2 Methods ................................................................................................................. 102 4.3 Results ................................................................................................................... 109 4.4 Discussion .............................................................................................................. 117 4.5 References ............................................................................................................. 120 Chapter 5: The Effect of Expectation on Caffeine Withdrawal Symptoms During a Blind Dose Taper (Study 4) .................................................................................. 121 5.1 Introduction............................................................................................................ 121 5.2 Methods ................................................................................................................