Christian Büchel is a Professor for Cognitive Neuroscience and the Director of the Department for Systems Neuroscience at the University Medical Center Hamburg-Eppendorf in Germany.
He investigates how higher cognitive processes such as learning are anchored in functional connections of the brain. His lab is mainly interested in pain, fear and decision making. Christian aims to identify mechanisms behind these phenomena using a multi-level approach: analysis of behavior and autonomic responses, computational modeling of the underlying algorithmic and neural processes, multimodal neuroimaging (fMRI and EEG) of these processes, and pharmacological challenges to investigate the causal role of specific neurotransmitter systems. His work not only contributes to our understanding of basic neuroscience mechanisms, but also provides novel ideas and approaches in clinical neuroscience, which could eventually improve prevention, diagnosis, prognosis and disease progression assessment in neuropsychiatric disorders including chronic pain.
Common mental disorders, such as depression or anxiety, are frequently associated with chronic conditions in the somatic domain, e.g. fatigue or pain. New approaches to diagnosis and treatment of complex combined (mental+somatic) conditions are required. Recently, computational concepts originating from a "Bayesian brain" perspective offer a novel perspective on how problems of mental and somatic health results from disturbances of brain-body interactions. This computational perspective highlights the close connection of mental health to how the brain perceives bodily states (interoception), elicits reactive and anticipatory actions to control bodily states (homeostatic/allostatic control), and monitors its own capacity of control (metacognition). Furthermore, this perspective provides a framework for developing new experimental interventions and computational assays as clinical tools.
Klaas Enno Stephan is a Professor for Translational Neuromodeling & Computational Psychiatry at the University of Zurich and ETH Zurich in Switzerland.
His scientific work covers the entire translational pipeline, from the development of disease theories via the creation of computational methods to their application in clinical studies. One of his central goals is the development of clinically useful “computational assays” for psychiatry and psychosomatics. Based on generative models of brain activity and behavior, his hope is that such assays will support more precise diagnostics and individualized treatment recommendations, leading to a transformation of clinical practice and redefinition of mental diseases. His track record includes pathophysiological theories of schizophrenia, fatigue and depression, the development of open source and widely used computational tools (e.g., for investigating brain connectivity and Bayesian model selection) as well as numerous studies on psychiatric and psychosomatic disease mechanisms.
There has been an increasing interest in the neurocomputational mechanisms underlying psychotic disorders in recent years. One promising approach is based on the theoretical framework of predictive processing, which proposes that inferences regarding the state of the world are made by combining prior beliefs with sensory signals. Delusions and hallucinations are the core symptoms of psychosis and often co-occur. Yet, different predictive-processing alterations have been proposed for these two symptom dimensions, according to which the relative weighting of prior beliefs in perceptual inference is decreased or increased, respectively. I will present recent behavioural, neuroimaging, and computational work that investigated perceptual inference to elucidate the changes in predictive processing that may give rise to psychotic experiences. Based on the empirical findings presented, I will provide a more nuanced predictive-processing account that suggests a common mechanism for delusions and hallucinations at low levels of the predictive-processing hierarchy, but still has the potential to reconcile apparently contradictory findings in the literature. This account may help to understand the heterogeneity of psychotic phenomenology and explain changes in symptomatology over time.
Philipp Sterzer is a psychiatrist, psychotherapist and a Professor of Psychiatry with a focus on Computational Neuroscience at the Charité in Germany.
He is dedicated to researching visual perception processes and their changes in mental disorders using functional imaging methods. Leveraging functional imaging methods such as tasl-based and resting-state fMRI, his work is specifically dedicated to the alteration of these visual perceptual processes in mental disorders, e.g. psychosis, depression, conduct disorder, and alcohol-use disorders. In his work, he also employs a predictive coding framework to understand his topics better.
Tor Wager is director of the Cognitive and Affective Control Laboratory and Diana L. Taylor Distinguished Professor in Neuroscience at Dartmouth College. His research focuses on the neurophysiology of affective processes such as pain, emotion, stress, and empathy - and how their expression is influenced by cognitive and social influences. Also, Dr. Wager and his lab are dedicated to developing analytical methods for functional neuroimaging and sharing ideas, tools, and scientific data with the scientific community and the public.
Harald Engler is a Professor for Behavioral Immunobiology at the Institute of Medical Psychology and Behavioral Immunobiology, Essen University Hospital in Germany.
The focus of his translational research is in the field of behavioral immunobiology and psychoneuroendocrinology. Together with his research group, he focuses on functional interactions between the peripheral immune system and the central nervous system in animal and human experiments and investigates their importance for the control of behavior and mental processes. A particular focus is on afferent and efferent communication pathways and the influence of inflammation on cognitive and affective processes. The goal of his research is a better understanding of molecular and neurobiological mechanisms relevant for the maintenance of mental health and for the development of neuropsychiatric diseases such as depression or schizophrenia.
Environmental context was recently described as a critical regulator of pain memory; both rodents and humans exhibit increased pain sensitivity in environments recently associated with a single painful experience. Previous work has also demonstrated that a context associated with presentation of a painful stimulus (e.g., a shock) in fear conditioning paradigms can cause a conditioned analgesia to develop in the presence of those contextual cues. It is unknown however, how repeated exposure to a painful stimulus in a distinct context modifies pain expression in that environment. To answer this question, we conditioned mice to associate distinct contexts with either repeated administration of a mild visceral pain stimulus (intraperitoneal injection of acetic acid) or vehicle injection over the course of three days. On the fourth day, animals received acetic acid injection in both the acid-trained and vehicle-trained chamber and were tested for mechanical sensitivity in each context. Both female mice and male mice develop a conditioned pain tolerance in this paradigm. We then showed that this effect is mediated endogenous opioid signaling and supported by different molecular mechanisms in males and females within the anterior cingulate cortex and the periaqueductal gray. Specifically, while males show tolerance-dependent decreased expression of perineuronal nets in the ACC, females show the opposite effect. Only males show elevated PNN expression within the PAG, however. Interestingly, tolerance was associated with decreased neural activity in each region in both males and females. These experiments suggest that pain-associated memory engages endogenous opioid systems to create a context-dependent conditioned compensatory response for painful stimuli.
Sydney Trask is an Assistant Professor for Neuroscience and Behavior at the Department of Psychological Sciences at Purdue University in the US.
She is interested in the ways the brain encodes, stores, retrieves, and updates memory, particularly in understanding memory for context, or the environment in which events take place. „Successful encoding and retrieval of context allows us to select and guide our behavior in a way that encourages situationally appropriate responding. However, alterations in this type of learning and memory are common in symptomology that underlies several neuropsychiatric disorders, ranging from PTSD to age-related dementia. Understanding how memory for context is formed, retrieved, and altered at both the circuit and molecular level, will provide one crucial step forward to treatments aimed at reducing maladaptive behaviors stemming from contextually inappropriate behaviors.
Opioid analgesics and endogenous peptides engage mu opioid receptor (MOR) signaling across multiple brain regions to alleviate pain. Notably, the ventrolateral periaqueductal gray (vlPAG) plays a dual functional role for both nociceptive processing and robust antinociception. However, the molecular identity, signaling dynamics, and plasticity of MOR+ neurons in vlPAG, as well as their role in pain and endogenous analgesia, remains unclear. Here, we characterized the nociceptive MOR+ neural populations in the vlPAG to gain insight into the molecular markers and temporal dynamics that define this functional ensemble. To this end, we employed mouse and viral genetic approaches to capture, monitor, and manipulate vlPAG cell-types at the intersection of nociception and molecular MOR expression across acute and inflammatory pain states. Using the targeted recombination in active populations (TRAP) approach, we found a gradient in pain-active vlPAG neurons that increased posteriorly, suggesting spatial heterogeneity in vlPAG with respect to pain processing. Next, we distinguished molecular markers of pain-active vlPAG MOR+ neurons, such as Vglut2 and Vgat, while further defining the projection targets of MOR+ cells using TRAP. Capitalizing on a MOR promoter-driven viral vector, we used in vivo fiber photometry imaging to record calcium transient activity reported by fluorescence of the genetically encoded calcium indicator GCaMP6f in MOR+ vlPAG neurons. With this approach, we discovered that vlPAG MOR+ neurons broadly demonstrate increased calcium activity in response to acutely noxious stimuli that was suppressed by morphine. Additionally, calcium activity in this population was enhanced following induction of Complete Freund’s Adjuvant inflammatory pain. In contrast to the MOR+ population, optogenetic activation of enkephalinergic interneurons in vlPAG produced antinociception during hotplate exposure indicating a potential local microcircuit that blunts the activity of nociceptive MOR+ neurons and associated pain behavior. Next, to assess endogenous opioid analgesia, we developed a novel non-pharmacological placebo model that utilizes instrumental conditioning to drive expectation-mediated analgesia. In our optimized endogenous analgesia conditioning (EAC) paradigm, we found that EAC mice prefer to spend significantly more time in the formerly innocuous paired context and display attenuated nocifensive behaviors, compared to non-conditioned controls, which correlated with reduced population calcium activity of MOR+ vlPAG neurons. Thus, the EAC model combined with cell-type specific viral tools for genetic access to opioidergic neural circuits serves as a strong platform to investigate the malleable nature of pain perception in preclinical pain models.
Gregory Corder is an Assistant Professor at the Department of Psychiatry and Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
Gregory’s research has aimed to uncover how brain and spinal cord circuitry converts emotionally sluggish nociceptive information into an affective painful experience. He has based his scientific interest on studying the fundamental properties of nerve circuits and how best to advance translational efforts to develop novel strategies for clinical pain relief. Gergory’s group is taking a comprehensive multidisciplinary approach to advance our understanding of how brain processes give rise to perceptions and motivations caused by endogenous and exogenous opioids in the brain's limbic and cortical circuits. The aim of their projects is to improve the mental, physical and social health of patients with chronic pain.
Website: Corder . Lab @ PENN
The brain constantly monitors the activity of the different physiological systems to form an updated image of one's state, a phenomenon known as interoception. This image is then used to regulate the organism's systems and maintain its internal balance. Immune activity is a critical component indicative of the internal state and a key executive arm, which is required to restore tissue homeostasis. I will discuss how the brain stores immune-related information and how it uses such information to regulate immunity. I will mainly focus on two central systems, the reward system, and the insular cortex.
Asya Rolls is a psychoneuroimmunologist, International Howard Hughes Medical Institute Investigator and an Associate Professor at the Immunology and Center of Neuroscience at Technion within the Israel Institute of Technology.
The focus of her team is to explore how the nervous system affects immune responses and thus physical health. Her recent work has highlighted how the brain's reward system is implicated in the placebo response and how brain-immune interactions can be harnessed to find and destroy tumors.
Placebo research has implications for the design, conduct and interpretation of clinical trials. Clinical trials should account for confounding factors (i.e. natural history and regression to the mean). An additional problem is the fact that positive prior experience creates strong expectations in the individuals receiving the active drug first as compared to those receiving the placebo first. Therefore, it is critical to measure expectations of research staff, study individuals and proxies. Yet, the predictive value of expectations and other factors remain unknown. In laboratory settings, research can be tailored to discover ramifications of the placebo phenomena and how these ramifications can be determined to inform the design and conduct of clinical trials as well as clinical practice. In this talk, I will outline the state-of-the-art of psychological and neurobiological underpinnings of predictors of placebo effects including sex, racial and ethnic disparities, psychological constructs and clinical phenotypes. The research findings will be presented in a way to illustrate implications on how to predict individual difference in placebo responsivity in clinical trials.
Luana Colloca is an MPower Distinguished Professor at the University of Maryland in the School of Nursing in the US.
Luana leads a research portfolio exploring endogenous pain perception, processing, and modulation in which the expectancy of analgesic relief, which can actually activate endogenous systems, is explored from a psychoneurobiological perspective from genetics to brain imaging. This also includes placebo/nocebo effects and other nonpharmacological interventions such as virtual reality. Her work on the neurobiological mechanisms of placebo and nocebo effects with an multifaced approach, including psychopharmacological, neurobiological and behavioral approaches, raises the possibility of unfolding the mechanisms of expectancy-induced analgesia with potential implications for pain management.
The recent systematic review and meta-analysis, which provided the basis for the latest recommendation on neuropathic pain pharmacotherapy, demonstrated large numbers needed to treat (NNT) for most neuropathic pain medications, compared with the previous guidelines. In addition, multiple recent clinical trials in neuropathic pain with preclinically promising drugs have failed. While we did not see a general increase in placebo responses over time, large placebo responses may cause low assay sensitivity of clinical trials. An inherent assumption in the RCT design is that the difference between the observed analgesic drug response and the observed placebo response can be attributed to the “true” pharmacological effect of the drug. This may not be the case in studies with high placebo responses. High placebo responses may have implications for the outcome of clinical trials, systematic reviews and evidence-based clinical treatment guidelines. The role of expectation for the placebo response will be discussed with examples from recent studies with cannabis-based medicine. I will also touch upon other reasons for the placebo response such as biased attention, regression towards the mean and inflation of baseline scores.
Nanna Finnerup is a Professor for Pain Research at the Danish Pain Research Center in the Department of Clinical Medicine at Aarhus University in Denmark.
Her main interest is the pathophysiology and therapy of neuropathic pain. Nanna seeks to understand the molecular mechanisms associated with pain caused by nerve injury. Current research areas include spinal cord injury pain, chemotherapy-induced neuropathic pain, painful diabetic polyneuropathy, postsurgical neuropathic pain, thermal sensory integration, neurophysiological assessment of pain mechanisms, placebo mechanisms, as well as neuropharmacology. For example, she studies genetic factors that may increase the risk of developing neuropathic pain caused by nerve injury, the aim being, in time, to contribute to design of precision medicine.
Various placebo-effects reduce the measurable effect size in clinical trials. Most of these are perceived effects, including baseline-inflation, regression to the mean, spontaneous remission of the disease, patients’ interest to please the doctor and rater bias for soft endpoints.In an attempt to optimize the success rates of trials with a risk of high placebo-effects, measures can and should be brought in place: de-linking primary endpoint from screening items, raters’ and participating patients’ training and supervision, central rating, the use of alternative harder (e.g. imaging or digital) endpoints, and the use of predictors for a high placebo effect as a statistical co-variate. These can individually lower placebo-effects by about 20%, but the additive effect of multiple measures is unfortunately lower. It is not understood why – also because we not have adequate studies evaluating the effects of such measures in a randomized fashion, e.g. in a “study within an trial” (SWAT).
Dr Peter Schüler, MD, is board certified in Neurology, Neurophysiology and Epilepsy (Germany) and in Pharmaceutical Medicine (Swiss Medical Board) and certified in Business Administration (Henley College, London). He started his academic career at University Hospital Erlangen, Germany, joined Pharmacia as Head Medical Affairs CNS for the German-speaking countries in 1995 and moved into the CRO business in 2000. In 2015 he was appointed Sr VP Drug Development Solutions Neurosciences at ICON.
He was involved in the design and conduct of various proof-of-concept, dose-finding and pivotal studies in nearly all CNS indications. He is editor of the Elsevier textbooks “Re-engineering clinical trials” in 2015 and in 2020 of “Innovation in Clinical Trial Methodologies”. He lectures Pharmaceutical Medicine at the University of Duisburg-Essen as Head Lecturer and acting-chair of the Scientific Course Committee and is invited lecturer at the European Center Pharmaceutical Medicine (ECPM) at the University of Basel, Switzerland. He was member of the DIA Regional Advisory Council EMEA from 2017 to 2021 and currently is President of the German Society for Pharmaceutical Medicine (DGPharMed).
Andrea Evers is a Professor for Health Psychology at the Institute of Psychology at Leiden University in the Netherlands.
Her research focuses on psychoneurobiological factors, such as stress and expectations, in health and disease. She has a specific interest in the psychoneurobiology of somatic complaints (e.g., pain and itch) and conditions (e.g., chronic inflammatory conditions), with particular emphasis on placebo effects, stress mechanisms, and treatments. Her research group conducts both fundamental research on the psychoneurobiology of placebo and stress mechanisms and translational research on screening and self-management or cognitive-behavioral interventions for healthy populations and chronic somatic conditions.
The patient-clinician interaction can powerfully shape treatment outcomes such as pain but is often considered an intangible “art of medicine” and has largely eluded scientific inquiry. Although brain correlates of social processes such as empathy and theory of mind have been studied using single-subject designs, specific behavioral and neural mechanisms underpinning the patient-clinician interaction are unknown. Using a two-person interactive design, we have constructed both a fMRI and EEG setup to simultaneously record hyperscan neuroimaging data from patient-clinician dyads, who interacted via live video (for fMRI) or face to face (for EEG), while clinicians treated evoked pain in patients with chronic pain. Our recently published fMRI results (Ellingsen et al., 2020, 2021) showed that patient analgesia was mediated by patient-clinician nonverbal behavioral mirroring and brain-to-brain concordance in circuitry implicated in theory of mind and social mirroring. Dyad-based analyses showed extensive dynamic coupling of these brain nodes with the partners’ brain activity, yet only in dyads with pre-established clinical rapport. These findings introduce a putatively key brain-behavioral mechanism for therapeutic alliance and psychosocial analgesia. This talk will supplement our previously published results with results from ongoing hyperscan EEG studies and introduce future directions for this nascent field of research.
Vitaly Napadow is a Professor for Radiology at Harvard Medical School in the US.
Somatosensory, cognitive, and affective factors all influence the malleable experience of chronic pain, and Vitaly’s Lab has applied human functional and structural neuroimaging to localize and suggest mechanisms by which different brain circuitries modulate pain perception. His neuroimaging research also aims to better understand how non-pharmacological therapies, from acupuncture and transcutaneous neuromodulation to cognitive behavioral therapy and mindfulness meditation training, ameliorate aversive perceptual states such as pain.
The interaction between a patient and caregiver shape placebo responses but the specific mechanisms are poorly understood. In a series of studies, we have investigated mechanisms associated with patient-clinician interactions and their effects on patient outcomes. Our most recent line of studies includes an individual patient-data meta-analysis (IPDMA) comparison of expectations in online versus face-to-face psychological treatments, treatment of experimental sickness with different types of physician interactions, as well as the role of media attention for expectations about drug efficacy and patient-clinician consultations. I will provide an overview of the results from our new studies and point to limitations and future directions for the science of patient-clinician interactions.
Karin Jensen is an Associate Professor for Clinical Neuroscience at the Department of Clinical Neuroscience at the Karolinska Institute in Sweden.
Her research group focuses on brain mechanisms involved in the experience of pain and placebo effects. Karin‘s work has challenged existing models of the placebo effect and contributed novel scientific data demonstrating that (a) placebos work outside of conscious awareness, (b) placebos work among patients with severe intellectual disabilities, and (c) placebo effects are shaped by subtle social cues between a patient and health-care provider. Karin adopts an evolutionary perspective of the placebo effect and studies placebos in previously understudied contexts such as psychotherapy, surgery and intellectual disability.
In clinical consultations, words matter. Words have the power to help patients, but also the power to harm. In this presentation, Dr van Vliet will provide an overview of how communication can elicit both placebo and nocebo-effects in clinical practice. To do so, she will focus on the topics of information-provision and clinician-expressed empathy. Join us to hear some of the latest insights on these topics from the field of communication research, as well as a glimpse into the future in which the research worlds of communication and placebo- and nocebo-effects can be further integrated.
Liesbeth Van Vlieth is an Assistant Professor for Health, Medical and Neuropsychology at the Department of Health, Medical and Neuropsychology at Leiden University in the Netherlands.
She studies how communication can heal and harm when patients are confronted with a serious, life-threatening illness. To do so, she combines insights from communication, palliative care, and placebo- / nocebo-effect research. Liesbeth is interested in the evidence-base of various communication elements, ranging from information-provision to clinician-expressed empathy. Most of her research focusses on oncology, but she also has expertise in the domains of neurology and pediatric palliative care. She is experienced in a range of quantitative and qualitative methodologies; from experimental video-vignette designs, observational studies, to clinical RCTs.
Ben Colagiuri is a Professor for Psychology in the School of Psychology at the University of Sydney in Australia.
His research explores how expectations influence human behavior. The majority of his research focuses on placebo and nocebo effects, with a special interest in placebo effects in randomized controlled trials and whether warning patients about side effects increases their occurrence or severity. Other interests include research methodology, psycho-oncology, and complementary medicine. To date, he has developed a number of novel experimental models to uncover the mechanisms of placebo and nocebo effects for pain, sleep, nausea, and related conditions. His current work is exploring how knowledge about placebo and nocebo effects could be used ethically to improve patient outcomes.
Siri Leknes is a Professor for Social and Affective Neuroscience at the University of Oslo in Norway.
The Leknes Affective Brain lab (LAB lab) studies how the brain and body give rise to pleasurable and painful feelings, and how these feelings are connected to decisions and behavior. One interdisciplinary project centered on the benefits of acute pain. LAB lab's main methodology is experimental psychopharmacology in healthy humans, often centered on understanding how opioids modulate pain and pleasure. In addition, the LAB lab studies modulation of pleasure and pain in opioid-treated clinical populations with and without chronic pain and substance use disorder. They currently study state-dependent effects of opioids and their relation to social support, stress and dopamine.
There is growing evidence that placebo and nocebo effects may be induced by observational learning. The first evidence was reviewed and summarized in the form of the social learning model of placebo effects (Bajcar & Bąbel, 2018), which included both the relationships confirmed in previous studies and hypothesized ones. Since the model was published, a significant body of research has emerged that either verified its assumptions or provided further data on placebo effects induced by observational learning. The main issues addressed by the recent evidence include differences between placebo and nocebo effects; involvement of different types of modeling (i.e., behavioral modeling, symbolic modeling, and verbal modeling); the role of expectancy; individual differences in observers, including empathy; and characteristics of the demonstrator (e.g., sex, social status, self-confidence). The talk will summarize the current state of the art on the role of observational learning in placebo effects, introduce the revised social learning model of placebo effects, and highlight its implications for further research and clinical practice.
Przemysław Bąbel is a Professor of Psychology at the Institute of Psychology of the Jagiellonian University in Kraków, Poland.
Przemysław conducts research on learning mechanisms of placebo effects on pain, pain memory, and psychological factors that alter pain perception. He is involved in the application of behavior analysis and memory psychology in education and therapy fields, including the treatment of chronic pain and people on the autism spectrum. With his team and collaborators, he is developing a theoretical framework of the learning theory of placebo effects.
Placebo effects have long been discussed as entailing a strong social component (e.g. Atlas, Trends Cogn Sci 2021, for review). One aspect that has been less well explored is that placebos can also be used to manipulate brain and cognitive processes in a way that allows to generate novel insights into their very function. In this talk, I will review such research, focusing on placebo analgesia, empathy for pain, and prosocial behavior. This shows that lowering our pain sensitivity using placebo analgesia may reduce empathy, influences how we share the pain of others, and has a profound impact on our prosocial helping behavior. These findings highlight the usefulness of placebos as an underexplored research method, enabling more causal-mechanistic insights into social cognition, brain processes, and behavior. They also have implications beyond basic research, e.g., in light of the opioid crisis. They suggest that lowering one’s pain may also impact social emotions and how we interact with others.
Claus Lamm is a Professor of Biological Psychology at the Faculty of Psychology at the University of Vienna in Austria.
Claus' research examines the psychological and biological mechanisms of social cognition and emotion. Apart from advancing insights into the neural and psychological foundations of social cognition and behavior, his goal is to foster a thriving interdisciplinary research environment that will lead to innovative and cutting-edge research in the domain of Social Cognitive Neuroscience. His scientific interests focuses on the neural underpinnings of empathy and prosocial behavior. This includes recent multi-modal investigations combining neuroimaging with psychopharmacology and psychoneuroendocrinology, as well as comparative approaches to test empathy and its precursors in ravens and dogs.
Ulrike Bingel is a Professor for Clinical Neurosciences at the University of Duisburg-Essen in Germany.
Ulrike’s research focuses on systems neuroscience and particularly on the interface between pain processing of the central nervous system and cognitive neuroscience. Her work has revealed critical insights into the neurobiological basis of placebo and nocebo responses, their interaction with active pharmacological treatments and implications of these findings for clinical practice. Leveraging behavioral paradigms, pharmacological modulations, as well as functional and structural brain imaging and being particularly intrigued by the reciprocal effects of pain and cognition, she and her group have a strong focus on translational questions such as the role of expectations and prior experiences on analgesic treatment outcomes.
Open-label placebo (OLP) treatment has demonstrated efficacy for many chronic and psychosomatic conditions. The underlying mechanisms of this paradoxical intervention are unclear, and the role of positive expectancy remains subject of debate. To explore potential OLP mechanisms, we carried out two studies that were embedded in a 6-week RCT (N = 308) comparing the effects of OLP to double-blind placebo (DBP) in irritable bowel syndrome. In study 1, n = 33 participants were interviewed about their experience with OLP or DBP. While none of the interviewees mentioned treatment expectations, they often discussed hope and curiosity as important factors. Unlike DBP participants, who easily accepted their treatment, often with enthusiasm, OLP participants expressed more ambivalence, neutrality or uncertainty. Furthermore, the counter-intuitive intervention seemed to prompt self-reflection and observation of their symptoms, behaviors and habits. While DBP participants showed a passive commitment to their treatment, OLP participants seemed to be more actively engaged. These qualitative results are supported by study 2, a hierarchical linear regression analysis of psychological OLP and DBP predictors in the above-mentioned RCT (n = 210). Here, higher pain catastrophizing was associated with less OLP improvement (ß = -0.46; p = .005), while higher visceral sensitivity was associated with better OLP improvement (ß = 0.37; p = .030), suggesting that a sense of hope, self-efficacy and flexible thinking may enhance OLP effects. Neither pain catastrophizing nor visceral sensitivity played a predictive role in DBP. These findings indicate that different psychological mechanisms may be involved in DBP and OLP effects.
Julia Haas is a clinical psychologist, therapist and postdoctoral researcher at the Beth Israel Deaconess Medical Center and the Harvard Medical School in the US.
Her research interests include placebo effects in mental health and psychosomatic conditions (e.g., insomnia and depression) as well as their underlying psychosocial placebo mechanisms. She is specifically involved in research on open-label placebos in irritable-bowel syndrome and studies comparing the effectivity of deceptive vs. honest placebos.
The first successful randomized clinical trial of open-label placebos was published in 2010. Since then, a dozen randomized trials have provided evidence that open-label placebos are a safe and effective treatment for a number of medical conditions, including irritable bowel syndrome, chronic low back pain, osteoarthritis of the knee, cancer-related fatigue, allergic rhinitis, menopausal hot flashes, and migraine headaches. But here is my confession: despite having served as a collaborator and co-author on several of these clinical trials, I still harbor doubts. Are the control conditions sufficiently robust? Should the lack of blinding undermine our confidence in the results? Are the effect sizes sufficiently large to warrant the use of open-label placebos? Do the apparent clinical benefits persist over time? Will clinicians be willing to openly prescribe placebos in routine clinical practice? Is the open-label placebo paradigm necessary, or are there other non-pharmaceutical methods for delivering similar healthcare benefits? And finally, although inert pills cannot, in and of themselves, produce side effects, does the use of open-label placebos carry risks of harm (e.g., could it undermine the patient-clinician relationship?). In this talk I will discuss these critiques in detail; and I will offer some correctives to move us toward the goal of either strengthening the evidentiary basis for open-label placebos and bringing them into mainstream clinical practice, or determining that we should move in a different direction, using what we have learned from the research on open-label placebos, but applying that knowledge in a different, more effective or more acceptable fashion.
John Kelley is Deputy Director of the Program in Placebo Studies at Harvard Medical School and Distinguished Professor of Psychology at Endicott College. He is also a past president of the Society for Interdisciplinary Placebo Studies. Professor Kelley and his colleagues investigate placebo and nocebo effects in medical and psychiatric disorders, with a particular focus on patient-clinician communication, the therapeutic relationship, and the role of expectancies in healthcare outcomes. His more recent research interests include open-label placebo and authorized concealment, which have the potential to reduce medication doses and decrease side effects, and perhaps even ameliorate the opioid crisis.
Biomedicine and placebo studies held a deeply belief that placebos “work” only placebos are administered with concealment in RCT or deceptive in laboratory experiments. Patients needed to believe that they were receiving medication for placebos to have benefits. A small and short OLP RCT of 2010 and a series of at least a dozen other such clinical trials has shown that placebo pills alone elicit benefits without deception, concealment or explicit conditioning with pharmaceuticals. Transparency and honesty were compatible with placebos treatment. As it generally does with anything placebo, biomedicine has so far ignored these findings. Placebo researchers are still trying to digest these data and its implications for placebo practice and theory. I will briefly mention how, in my opinion, OLP, what I would call the naked ritual of healing, may promote a broader understanding of placebo and, at the same time, be disruptive.
Ted J. Kaptchuk is a Professor of Medicine and of Global Health and Social Medicine at Harvard Medical School in the US.
Ted’s career has spanned multiple disciplines, drawing upon concepts, research designs and analytical methods from the humanities and basic and clinical and social sciences. He investigates the impact of placebos in various illnesses, the neurobiology of placebo effects, the experience of patients being treated by placebo, open-label placebos, and various psychological, cultural, sociological and philosophical dimensions of placebos. Furthermore, he is doing theoretical work on the histories of placebo controls and the placebo effect, and significant ethical analyses of the use of placebos in clinical practice and research.
Yvonne Nestoriuc has been Professor of Clinical Psychology at the Faculty of Humanities and Social Sciences at Helmut Schmidt University in Hamburg since September 2018. She conducted research on expectancy management as a postdoctoral fellow at Harvard Medical School in Boston and at Philipps-Universität Marburg. From 2013-2016, she was an assistant professor at the Institute of Psychology at the University of Hamburg and from 2016-2018, she was a professor and senior psychologist at the Institute and Polyclinic for Psychosomatic Medicine and Psychotherapy at UKE. Her research interests include placebo and nocebo effects, risks and side effects of psychotherapy, and psychosocial stress in cancer patients.
Just as placebo effects demonstrate that the effects of any medicine or treatment are determined, in part, as a result of the psychological and social context in which they are experienced, the total effect of anything (e.g., the effects of exercise, diet, our genetics, a broad illness or a global pandemic) can also be influenced by placebo-like or “placebic” effects. This talk will discuss the overarching framework of mindset in driving such effects. I will review current thinking regarding what a mindset is and how mindsets are related to-yet distinct from-other psychological variables such as expectations and personality. Within the talk, I will cover a selection of empirical studies demonstrating how mindsets can influence health outcomes in a range of domains both within and beyond medicine via affective, attentional, behavioral and physiological mechanisms.
Alia Crum is an Associate Professor for Psychology and Medicine at Stanford School of Humanities and Sciences in the US.
Her research focuses on how changes in subjective mindsets - the lenses through which information is perceived, organized, and interpreted - can alter objective reality through behavioral, psychological, and physiological mechanisms. Her work is also inspired by research on the placebo effect, a remarkable and consistent demonstration of the ability of the mindset to elicit healing properties in the body. She is interested in understanding how such mindsets affect important outcomes outside the realm of medicine, in the domains of behavioral health and organizational behavior. More specifically, she aims to understand how mindsets can be consciously and deliberately changed through intervention to affect organizational and individual performance, physiological and psychological well-being, and interpersonal effectiveness.
Philip Hurst is a Senior Lecturer in Sport and Exercise Psychology. He teaches in the Sport and Exercise Psychology, Sport and Exercise Science, and Sport Therapy and Rehabilitation programs. His research examines the role of the psyche in the effectiveness of performance-enhancing substances and the psychological antecedents of substance use, as well as looking at placebo effects, safety measures in sport, and doping in sport.
Winfried Rief is Professor of Clinical Psychology and Psychotherapy and heads the institute of the same name at Philipps University Marburg as well as the Psychotherapy Outpatient Clinic at Philipps University as a psychological psychotherapist and supervisor. Professor Rief's research focuses on somatoform dysfunction, placebo and nocebo effects, optimisation of clinical trials and interventions, as well as pain, eating disorders and anxiety disorders. He is a member of the WHO/APA Expert Commission on Classification of Mental Disorders according to DSM-V and co-chair of the WHO Working Group on Pain Diagnosis in ICD-11 and spokesperson for the supraregional DFG Research Group on Placebo and Nocebo Mechanisms as well as a DFG review board member.
In 2014 Flint Michigan switched its water supply and caused a significant spike in lead levels and two outbreaks of Legionnaires disease that killed at least 13 people. What came to be known as “the Flint Water Crisis" caused large increases in Federal and State financial support, with over $1.2 billion in relief funds as well as a flurry of legal suits. Early reports attributed the increasing rates of special education enrolment and diagnoses of learning disabilities in Flint children to lead exposure from the Water Crisis. But was this conclusion justified? Working with a team of water engineers from Virginia Tech University, I try to unravel whether the worsening educational outcomes were due to lead poisoning, or one of the largest documented nocebo effects in American history.
Negative beliefs about COVID-19 vaccine side-effects spread rapidly through social communication. We tested if pre-vaccination social communications about side-effects from personal acquaintances, news reports, and social media predict post-vaccination side-effect experiences. Further, we assessed if expectations mediate the relationships between social communication and side-effect experience. In a prospective longitudinal survey (N=551), COVID-19 vaccine side-effect information from three sources—social media posts, news reports, and accounts from personal acquaintances—as well as side-effect expectations, were self-reported pre-vaccination. Vaccination side-effects were assessed post-vaccination. Social media post views and personal acquaintance communications significantly predicted an increase in pre-vaccination side-effect expectations, and the same variables predicted experienced side-effects. Moreover, pre-vaccination side-effect expectations fully mediated the relationship between both sources of social communication and experienced side-effects following vaccination. This study identifies new links between personal acquaintance and social media communications and vaccine side-effect experiences and finds that pre-vaccination expectations account for these relationships. Modifying side-effect expectations through these channels may change side-effects following COVID-19 vaccinations as well as other publicly discussed vaccinations.
Evidence from nocebo and psychosomatic research indicates that health beliefs have a significant impact on physical health. Specifically, believing one will develop symptoms makes the experience of such symptoms more likely. However, what specific health belief underlies this effect, and can it predict the experience of unexplained symptoms? Building on nocebo research and our framework of beliefs as higher-order predictions[1,2], we took advantage of COVID-19 to answer these questions. Utilizing two longitudinal studies with over 300 participants, we (A) identified a particular belief regarding estimated COVID-19 symptom severity as the only belief-related factor associated with symptom experience. (B) demonstrated that this belief predicts COVID-like symptoms 3-4 weeks later. Our findings, which were pre-registered and replicated in a separate cohort, also reveal a novel construct reflecting perceived susceptibility to illnesses, which fully mediated this effect. Taken together, our findings contribute to the understanding of the development of unexplained symptoms, and could inform future belief-modifying interventions aimed at improving well-being. We will also discuss our ongoing work on extending these findings to daily well-being beyond COVID-19.
Clinicians have a responsibility to inform patients about possible side effects, yet merely telling patients what symptoms are possible can increase nocebo effects. Furthermore, concerns about side effects are a major barrier to vaccination against viruses COVID-19. In this randomized controlled trial, participants (N=528) who had just received the second COVID-19 vaccine shot were either assigned to watch a short video about side effects (in addition to receiving the standard, written information about side effects) or received only the standard written information about side effects. Intervention participants watched a 4-minute video describing how minor side effects are a positive sign that the vaccine is working and the body is building immunity. Compared to the treatment-as-usual control participants, those exposed to the mindset that “symptoms are positive signals” experienced fewer symptoms immediately after vaccination, were less worried about symptoms three days later, and had increased intentions to vaccinate against COVID-19-like viruses in the future. This brief, scalable intervention is an encouraging solution to keeping patients informed without increasing nocebo effects. This talk will discuss the evidence and consideration of using this approach in clinical practice, particularly in relation to vaccines.
Among the many challenges of the COVID-19 pandemic, a crucial question is whether and to what extent the fear and expectation of contracting SARS-CoV-2 can influence individual perception of health. Since COVID -19 and influenza-like illness have similar clinical manifestations, it is reasonable to expect that individuals who interpret their symptoms with stronger beliefs and fear of being infected with COVID-19 would perceive their health to be poorer than those who have no expectations. 967 citizens with suspected COVID -19 symptoms who came for COVID-19 test, were surveyed online using Qualtrics barcode. Data from 523 citizens (283F) resulting negative for COVID -19 were entered into a structural equation model. Fear and belief of having COVID -19 accounted for 60% of the variance in perceived health. Despite not having COVID-19, individuals who interpreted their symptoms with a stronger belief and fear of being infected with SARS-CoV-2 perceived a higher number and more severe COVID -like symptoms.
The results suggest the occurrence of nocebo effects during the pandemic. The nocebo component affects how people perceive their health and, therefore, healthcare system costs by increasing the number of people requesting a COVID -19 test.