A placebo effect is a real and beneficial psychobiological phenomenon following the administration of a substance or procedure that has no inherent power to produce an effect. Nocebo effects, on the other hand are genuine and detrimental psychobiological phenomenon following the administration of and inert substance or procedure. These effects have been extensively studied but are not well understood. Central to the development of a placebo effect is the anticipation of benefit or the anticipation of harm. Indeed, expectancy and conditioning are thought to be the two primary mechanisms involved in the acquisition of the placebo effect. The neurotransmitter Dopamine (DA) is integral to expectancy and reward and as such has recently been considered a key player in the mechanisms of the placebo effect. Based on this line of inquiry this study sought to investigate the role DA might have in the development of the placebo effect as observed in pain using an animal (mouse) model. It was proposed that DA is involved in the acquisition and maintenance of the placebo effect. Specifically it was proposed that the DA agonist cocaine would enhance the magnitude and duration of the placebo analgesia and that the DA antagonists SCH23390 and eticlopride would together or separately block the acquisition of the placebo analgesia. These proposals were assessed by utilizing supra-spinal (hotplate) and spinal (tail flick latency) protocols. Results indicated that cocaine enhanced placebo analgesia in spinal but not supra-spinal measures and that the DA antagonists SCH23390 and eticlopride each contributed to the acquisition, rather than the blockade, of placebo analgesia in both spinal and supra-spinal models. In fact, the most profound effect was observed when both antagonists were administered together rather than separately on supra-spinal measures but not spinal measures resulting in an enduring nocebo effect contradicting all predictions. The novel results presented in this study raises more questions than they answer, warranting more detailed exploration of the mechanisms of DA and its relationship with placebo effects.

The placebo effect represents a fascinating example of how cognition can influence the physiology of the brain and body. The expectation of therapeutic benefit elicited by a placebo given in the guise of active medication has been proposed to be a form of reward expectation, and is associated with activation of brain reward circuitry. Prominent placebo effects occur in Parkinson’s disease (PD), where the expectation of symptom improvement stimulates dopamine release in the striatum. In the work described in this dissertation, positron emission tomography with [¹¹C] raclopride was used to investigate the relationship between the strength of expectation of benefit and the degree of dopamine release in PD, and how this relationship corresponds to current models of dopamine function in reward. Chapter 3 describes a pilot study conducted in patients who had undergone subthalamic nucleus deep-brain stimulation (STN-DBS) in which we examined how awareness of stimulator status (ON or OFF) affected synaptic dopamine levels compared to when subjects were blind. No difference was detected between conditions; however, it proved to be difficult to maintain blinding due to the profound effects of STN-DBS. Chapter 4 describes the development of the methodology for the analysis of high-resolution PET data, in which we utilized the combined efforts of neuroscience and imaging physics to optimize the analysis of [¹¹C] raclopride PET data. In Chapter 5, I describe the use of verbal instructions to manipulate patients’ expectations in order to investigate how the likelihood of receiving levodopa influenced dopamine release when the patients were in fact given placebo. Placebo-induced dopamine release was differentially modulated by expectation in the dorsal and ventral striatum: dopamine release in the putamen was related monotonically to expected reward value, whereas dopamine released in the ventral striatum reflected the uncertainty of benefit or the salience of the expectation. The placebo effect in PD therefore involves at least two related but separate mechanisms: the expectation of benefit itself, which is scaled to reflect the value of the drug to the patient and is mediated by nigrostriatal dopamine, and the uncertainty or salience of benefit that is mediated by mesolimbic dopamine.

The placebo effect represents a fascinating example of how cognition can influence the physiology of the brain and body. The expectation of therapeutic benefit elicited by a placebo given in the guise of active medication has been proposed to be a form of reward expectation, and is associated with activation of brain reward circuitry. Prominent placebo effects occur in Parkinson’s disease (PD), where the expectation of symptom improvement stimulates dopamine release in the striatum. In the work described in this dissertation, positron emission tomography with [¹¹C] raclopride was used to investigate the relationship between the strength of expectation of benefit and the degree of dopamine release in PD, and how this relationship corresponds to current models of dopamine function in reward. Chapter 3 describes a pilot study conducted in patients who had undergone subthalamic nucleus deep-brain stimulation (STN-DBS) in which we examined how awareness of stimulator status (ON or OFF) affected synaptic dopamine levels compared to when subjects were blind. No difference was detected between conditions; however, it proved to be difficult to maintain blinding due to the profound effects of STN-DBS. Chapter 4 describes the development of the methodology for the analysis of high-resolution PET data, in which we utilized the combined efforts of neuroscience and imaging physics to optimize the analysis of [¹¹C] raclopride PET data. In Chapter 5, I describe the use of verbal instructions to manipulate patients’ expectations in order to investigate how the likelihood of receiving levodopa influenced dopamine release when the patients were in fact given placebo. Placebo-induced dopamine release was differentially modulated by expectation in the dorsal and ventral striatum: dopamine release in the putamen was related monotonically to expected reward value, whereas dopamine released in the ventral striatum reflected the uncertainty of benefit or the salience of the expectation. The placebo effect in PD therefore involves at least two related but separate mechanisms: the expectation of benefit itself, which is scaled to reflect the value of the drug to the patient and is mediated by nigrostriatal dopamine, and the uncertainty or salience of benefit that is mediated by mesolimbic dopamine.

The placebo effect represents a fascinating example of how cognition can influence the physiology of the brain and body. The expectation of therapeutic benefit elicited by a placebo given in the guise of active medication has been proposed to be a form of reward expectation, and is associated with activation of brain reward circuitry. Prominent placebo effects occur in Parkinson’s disease (PD), where the expectation of symptom improvement stimulates dopamine release in the striatum. In the work described in this dissertation, positron emission tomography with [¹¹C] raclopride was used to investigate the relationship between the strength of expectation of benefit and the degree of dopamine release in PD, and how this relationship corresponds to current models of dopamine function in reward. Chapter 3 describes a pilot study conducted in patients who had undergone subthalamic nucleus deep-brain stimulation (STN-DBS) in which we examined how awareness of stimulator status (ON or OFF) affected synaptic dopamine levels compared to when subjects were blind. No difference was detected between conditions; however, it proved to be difficult to maintain blinding due to the profound effects of STN-DBS. Chapter 4 describes the development of the methodology for the analysis of high-resolution PET data, in which we utilized the combined efforts of neuroscience and imaging physics to optimize the analysis of [¹¹C] raclopride PET data. In Chapter 5, I describe the use of verbal instructions to manipulate patients’ expectations in order to investigate how the likelihood of receiving levodopa influenced dopamine release when the patients were in fact given placebo. Placebo-induced dopamine release was differentially modulated by expectation in the dorsal and ventral striatum: dopamine release in the putamen was related monotonically to expected reward value, whereas dopamine released in the ventral striatum reflected the uncertainty of benefit or the salience of the expectation. The placebo effect in PD therefore involves at least two related but separate mechanisms: the expectation of benefit itself, which is scaled to reflect the value of the drug to the patient and is mediated by nigrostriatal dopamine, and the uncertainty or salience of benefit that is mediated by mesolimbic dopamine. / Medicine, Faculty of / Graduate

AD/HD medications are shown to be significantly more successful at enhancing attention/concentration performance in individuals with AD/HD than placebo treatments. Few studies, however, have investigated the possibility of a placebo reaction in both medication and placebo groups by comparing placebo treatments to no treatment at all. Using an undergraduate population, I evaluated the effect of expectations about a treatment's efficacy on performance in an attention/concentration task. In addition to cognitive performance outcome measures, I included several physiological measures, such as heart rate variability (HRV) through respiratory sinus arrhythmia (RSA). Contrary to expectations, no differences were observed in performance on attention tasks or physiological measurements as a result of the believed efficacy of an orally administered placebo treatment.

Background: The placebo effect and the placebo response is a misunderstood phenomenon and their potential is wildly underestimated. Most people, including health care professionals, consider the placebo effect to be a “make believe” effect which only affects gullible people. It is argued that the nurse is in an unusually advantageous position to observe and facilitate the placebo effect and make use of the benefits for the patients. Observation of said response is made by many authors but there is little to no research on the placebo effect from a nursing standpoint. Some of the research results can however be translated to the nurse profession and used in clinical settings. Aim: The purpose is to describe areas where the placebo effect may affect nursing of the patient. Method: A literature review format was chosen to comprise existing knowledge on the placebo effect, which can be applied for nursing. Results: Themes that arose from examination of chosen literature included: Emotional state, Expectation and Conditioning, Conscious and Social learning and Patient-caregiver relationship. Many of the observed interventions could be applied using the nursing philosophy of Hildegard Peplau. Conclusion: The placebo effect can be used by the nurse to improve the result of the patient´s treatment. If placebo becomes a focus in nursing research the results could be more applicable to benefit patients than if researched by other professional groups.

Thesis advisor: Ronald K. Tacelli / This dissertation arose from concerns that the prevalent philosophy of materialism which reduces everything to matter has inadvertently contributed to the ecological destruction of the planet, and an impoverished understanding of human nature. Conceptual arguments and empirical data cry out for a philosophy beyond materialism (or its current avatar Physicalism) that moves us beyond 17th century classical science, making use of 20th century quantum science to better understand our world. Such a new philosophy would embed a new scientific paradigm that incorporates both the first person point of view and the third person "no point of view."The main issue I engage in this dissertation is whether consciousness can be explained by Physicalism. While functionalism, the dominant theory of Physicalism, answers many questions related to consciousness, it leaves major ones unanswered. I offer a critique of Physicalism using conceptual arguments and empirical data encompassing what I call the "chemistry of attention." I also offer innovative proposals toward a philosophical approach I term "Aspect Monism" that builds on earlier monist philosophies (Spinoza) while incorporating dualistic features, suggesting that this new approach would better account for consciousness. The proximate history of Physicalism to either explain the mind away or reduce it to the brain from Behaviorism through Identity Theory to Functionalism is laid out as well as the difficulty in establishing the boundaries of Physicalism.The project utilizes conceptual arguments to critique Physicalism in three areas of concern: What is left out? What is assumed? What is causing methodological confusion? The areas of qualia, cognition, intentionality, meaning and personhood are left out. This is demonstrated, in part, by various thought experiments like the inverted spectrum argument, the Chinese nation argument, the zombies' argument, the knowledge argument and the Chinese room argument. The problem of causal closure of the physical is that which is assumed. The ambiguity with respect to method is that which causes confusion.Empirical data from the neurosciences (EEG, ERP, fMRI experiments during meditation; OCD and phobia treatment; placebo and nocebo effect) are used to critically analyze Physicalism with respect to mental states and causation and the analysis of such data points to a close relationship between attention and changes in the brain, and subsequently to the collapse of Physicalism into Epiphenomenalism. Such a metaphysical approach to consciousness is suggested from, and provides a home for, the neurophysical approaches to the origins of consciousness. I present a neuro-quantum perspective using Stapp and Penrose-Hameroff who suggest these origins via neuroscience and quantum physics.As we search for a new scientific paradigm and consequently a new metaphysics that takes into consideration the objective and the subjective, and the inner and the outer, a new philosophy and a new scientific paradigm which incorporates both the first person point of view and the third person "no point of view" data is the need of the hour. / Thesis (PhD) — Boston College, 2011. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Philosophy.

Recently the question of eco-labelling has become increasingly important, especially when used as a green marketing tool. Surprisingly, the marketing placebo effect of eco-labelling and the influence it has on the performance of a product has received little attention. The purpose of this study is to explain the placebo effect of eco-labelling on consumer attitudes. Fishbein’s model of attitudes is implemented whereby a focus group is used as a basis to create a questionnaire and a tasting experiment. The findings of the study provide an explanation and evidence of the placebo effect of eco-labelling. The product with an environmental label is perceived as tastier, healthier and of higher quality than the same product without ecological label.

Fragile X Syndrome (FXS) is a disorder caused by a congenital mutation of the FMR1 gene on the X chromosome. FXS is associated with moderate to severe intellectual disability and is one known cause of autism spectrum disorders. There are no approved medications to treat FXS symptoms. In 2013, Seaside Therapeutics completed two Phase 3 studies of an investigational medication, STX209, for treatment of social withdrawal in FXS. Efficacy results for these studies were not positive. Clinical trials of psychoactive drugs often fail to show a statistical difference from placebo controls and a robust response to placebo is often cited as a reason for the failure. Retrospective studies of baseline variables in clinical trials have identified characteristics that were associated with an increased likelihood of responding to placebo. Such information is valuable for the design of future clinical trials and no such studies have been conducted in FXS. This study was a post-hoc analysis of data from Seaside Therapeutics' Phase 3 clinical trials in FXS. Baseline variables for subjects receiving placebo were pooled for analysis. To determine if a subject responded to placebo, the parent-rated ABC-SA and the ABC-IR were used. Clinician-rated assessments, including the CGI-S and CGI-I, were examined as well. Two-sample t-testing, one-way ANOVA testing, and correlation coefficients were calculated to compare the responses of subjects with different baseline characteristics. General linear regression modeling was used to determine if there were multiple baseline variables that could predict placebo response. Logistic regression modeling was used to determine if the baseline variables could predict whether a subject had a higher chance of being a treatment responder. A total of 287 subjects were randomized and completed the Phase 3 studies. Analyses for this study were conducted in a subgroup containing 106 subjects who received placebo. 76% improved during the study on the ABC-SA, indicating that there was a strong placebo effect on the study. None of the dichotomous baseline variables were associated with statistically significant differences in ABC-SA, ABC-IR, CGI-S, or CGI-I scores. Placebo-treated subjects in the 209FX302 study who were taking antipsychotics improved less on the CGI-S than those not on those medications. A similar pattern was observed on the ABC-IR and ABC-SA. Other categorical baseline variables were tested and there was no difference in the mean changes. The CGI-S score at baseline appeared to predict a statistically significant difference in the ABC-IR as more severe subjects were more likely to show a larger change in the ABC-IR. Similar, although not statistically significant results were seen with ABC-SA, CGI-I, and CGI-S changes, in that more severe subjects had greater responses to placebo. ABC-IR score changes were correlated independently with each of the ABC-C subscales but also with parental distress, CGI-S, and VAS-Anxiety. Only one variable, the ABC-IR at baseline, was significantly correlated with the ABC-SA score change, the rest of the variables were not significant. A multiple linear regression model predicting placebo response for the ABC-SA included only the baseline ABC-SA score. When the studies were modeled separately, the 209FX302 model contained additional variables including gender, antipsychotic use, and ABC-stereotypy scores. For the ABC-IR change model, the highest correlation coefficient was found in the 209FX301 study with ABC-IR, gender, Vineland-communication, maternal FMR1 status, and ABC-SL included in the model. 70% of the placebo treated subjects improved on the ABC-SA by at least 25%. Placebo responders were less frequently observed in clinician-rated assessments such as the CGI-I and CGI-S. In logistic regression models, for the ABC-IR response, a higher score on the hyperactivity subscale of the ABC-C was predictive of a lower placebo response. The CGI-S model was statistically significant and included the subject's age, race and ABC-IS score. The ABC-SA response could be modeled only in the 209FX302 study with gender and ADHD medication use remaining in the model. Also in the 209FX302 study, subjects were far less likely to be a responder on the ABC-IR or a total responder, if they were taking antipsychotic medications. Results of this study indicate that the ABC-SA is not recommended in future trials in the FXS patient population. Future trials should also allow ADHD and antipsychotic medication use as they were associated with a lower placebo response in some analyses. In addition, due to their inclusion in regression models, future studies should consider baseline variables such as parental stress and Vineland scores, and when designing study eligibility criteria or stratification variables.

The environmental concern has become a well discussed topic within today’s society and as a result awareness of the impact human behaviour has on the environment is continuously increasing. This concern is something companies take advantage of when marketing, as for instance by promoting their products or services as eco-labelled. Eco-labelled products have further shown to involve a lot of consumer opinions, and are thus common to study in relation to consumer attitudes. Theories also show that eco-labelled goods have been idealised in favour of conventional ones, referred to as a marketing placebo effect. In connection to this, companies have started to point interest at eco-labelled technology, which has become a recent phenomenon attracting attention. Nonetheless, the existing theory regarding this phenomenon has been mainly applied on specific areas, such as the food industry. The purpose of this study was therefore to explain the marketing placebo effect on eco-labelled technology. 162 experiments were conducted using one experiment group and one control group, in order to be able to detect an eventual marketing placebo effect when implementing an eco-label, using attitudes as an influencer. Based on the results, it was revealed that attitudes are crucial to take into consideration when applying an eco-label in a technology context. This as it was concluded that attitudes act as a trigger evoking a marketing placebo effect. The findings from this study contradicts current theories on how different factors cooperate in the process of a marketing placebo effect, and advances has thus been made in how the marketing placebo effect works when applied in a technology context.