The Use of Authorized Concealment to Minimize Nocebo Side Effects: A Survey of US Public Attitudes.

INTRODUCTION: To minimize nocebo effects, it may be possible to employ authorized concealment, in which clinicians tell patients about the nocebo phenomenon and ask if they would prefer not to be informed about mild treatment side effects. OBJECTIVE: The objective of the study was to understand public evaluations of authorized concealment for reducing nocebo effects. METHODS: An online cross-sectional survey was completed by a demographically diverse US national community sample between June 2 and 6, 2023. Participants were 1,012 adults residing in 48 states, ages ranging from 18 to 94 (mean = 43.2), 65.4% regularly taking medication, and 66.6% reporting a chronic physical or mental health condition. After learning about nocebo effects, participants rated and estimated their likelihood of consenting to four potential methods for authorized concealment of mild side effects. The four methods were ranked for preference and ranked again with the options of (1) receiving all side-effect information and (2) having the opportunity to select among disclosure methods. RESULTS: A majority of participants (86.2%) positively endorsed at least one authorized concealment method and 88.2% estimated they would consent to at least one method. Authorized concealment in which individuals learned only the most common side effects or had side-effect information available online received more positive ratings and rankings. A final ranking yielded preferences for receiving all side-effect information (30.4%) and having the opportunity to select side-effect disclosure method (31.8%). CONCLUSIONS: Our study suggests that many in the public could be open to authorized concealment for mild side effects when it is explained in reference to nocebo effects.

Development of a Measure of Fearful Implicit Associations with Dental Stimuli in Youth.

Youth with dental anxiety are at an increased risk of poor oral health but current tools used to identify dental anxiety in children in clinical settings are hampered by several limitations. This study assessed the psychometric properties of a measure of implicit associations with dental stimuli, the Affective Misattribution Procedure for dental stimuli (AMP-D) in 68 youth between the ages of 9 and 17 years. Measures of self-reported dental anxiety and parental perceptions of child dental anxiety were also administered. The internal consistency of the AMP-D was high (KR-20 = 0.96) and 1-week test-retest reliability was in the acceptable range (r = 0.75). The AMP-D was correlated with self-reported dental anxiety, providing evidence of construct validity. The psychometric properties of the AMP-D suggest it could be a useful tool in identifying youth with dental anxiety, particularly when concerns regarding self-representation may compromise the validity of self-reported anxiety.

Do Side Effects to the Primary COVID-19 Vaccine Reduce Intentions for a COVID-19 Vaccine Booster?

BACKGROUND: Vaccines are being administered worldwide to combat the COVID-19 pandemic. Vaccine boosters are essential for maintaining immunity and protecting against virus variants. The side effects of the primary COVID-19 vaccine (e.g., headache, nausea), however, could reduce intentions to repeat the vaccination experience, thereby hindering global inoculation efforts. PURPOSE: The aim of this research was to test whether side effects of a primary COVID-19 vaccine relate to reduced intentions to receive a COVID-19 booster. The secondary aim was to test whether psychological and demographic factors predict booster intentions. METHODS: Secondary data analyses were conducted on a U.S. national sample of 551 individuals recruited through the online platform Prolific. Key measures in the dataset were side effects reported from a primary COVID-19 vaccination and subsequent intentions to receive a booster vaccine. Psychological and demographic variables that predicted primary vaccination intentions in prior studies were also measured. RESULTS: Booster intentions were high. COVID-19 booster vaccine intentions were uncorrelated with the number of side effects, intensity of side effects, or occurrence of an intense side effect from the primary COVID-19 vaccine. Correlational and regression analyses indicated intentions for a booster vaccination increased with positive vaccination attitudes, trust in vaccine development, worry about the COVID-19 pandemic, low concern over vaccine side effects, and democratic political party affiliation. CONCLUSIONS: Side effects of a primary COVID-19 vaccine were not directly associated with lower intentions to receive a booster of the COVID-19 vaccine early in the pandemic. However, many variables that predict primary vaccination intentions also predict booster intentions.

The influence of message framing on nocebo headaches: Findings from a randomized laboratory design.

Attribute framing presents an ethically sound approach for reducing adverse nocebo effects. In past studies, however, attribute framing has not always decreased nocebo effects. The present study used a sham tDCS procedure to induce nocebo headaches to explore factors that may contribute to the efficacy of attribute framing. Participants (N = 174) were randomized to one of three between-subject conditions: a no-headache instruction (control) condition and two conditions in which headaches were described as either 70% likely (negative framing) to occur or 30% unlikely (positive framing) to occur. Results revealed nocebo headaches in both framing conditions, as compared to the control condition. Attribute framing did not influence headache measures recorded during the sham tDCS task, but framing did have a modest influence on one of two headache items completed after the task. Results suggest that attribute framing could have a stronger influence on delayed nocebo effect measures or retrospective symptom reports; a finding that may explain inconsistencies in the existing framing-nocebo effect literature. Exploratory analyses also revealed that low negative affect was associated with stronger nocebo and attribute framing effects, although these effects were found on only a few headache measures. It is concluded that researchers should further investigate the influence of attribute framing on nocebo headaches as a function of both timing and emotional factors.

Using Positive Attribute Framing to Attenuate Nocebo Side Effects: A Cybersickness Study.

BACKGROUND: Side effect warnings can contribute directly to their occurrence via the nocebo effect. This creates a challenge for clinicians and researchers, because warnings are necessary for informed consent, but can cause harm. Positive framing has been proposed as a method for reducing nocebo side effects whilst maintaining the principles of informed consent, but the limited available empirical data are mixed. PURPOSE: To test whether positive attribute framing reduces nocebo side effects relative to negative framing, general warning, and no warning. METHODS: Ninety-nine healthy volunteers were recruited under the guise of a study on virtual reality (VR) and spatial awareness. Participants were randomized to receive positively framed ("7 out of 10 people will not experience nausea"), negatively framed ("3 out of 10 people will experience nausea"), general ("a proportion of people will experience nausea"), or no side effect warnings prior to VR exposure. RESULTS: Receiving a side effect warning increased VR cybersickness relative to no warning overall, confirming that warnings can induce nocebo side effects. Importantly, however, positive framing reduced cybersickness relative to both negative framing and the general warning, with no difference between the latter two. Further, there was no difference in side effects between positive framing and no warning. CONCLUSIONS: These findings suggest that positive framing not only reduces nocebo side effects relative to negative framing and general warnings, but actually prevents nocebo side effects from occurring at all. As such, positive attribute framing may be a cheap and ethical way to reduce nocebo side effects.

What Should Clinicians Tell Patients about Placebo and Nocebo Effects? Practical Considerations Based on Expert Consensus.

INTRODUCTION: Clinical and laboratory studies demonstrate that placebo and nocebo effects influence various symptoms and conditions after the administration of both inert and active treatments. OBJECTIVE: There is an increasing need for up-to-date recommendations on how to inform patients about placebo and nocebo effects in clinical practice and train clinicians how to disclose this information. METHODS: Based on previous clinical recommendations concerning placebo and nocebo effects, a 3-step, invitation-only Delphi study was conducted among an interdisciplinary group of internationally recognized experts. The study consisted of open- and closed-ended survey questions followed by a final expert meeting. The surveys were subdivided into 3 parts: (1) informing patients about placebo effects, (2) informing patients about nocebo effects, and (3) training clinicians how to communicate this information to the patients. RESULTS: There was consensus that communicating general information about placebo and nocebo effects to patients (e.g., explaining their role in treatment) could be beneficial, but that such information needs to be adjusted to match the specific clinical context (e.g., condition and treatment). Experts also agreed that training clinicians to communicate about placebo and nocebo effects should be a regular and integrated part of medical education that makes use of multiple formats, including face-to-face and online modalities. CONCLUSIONS: The current 3-step Delphi study provides consensus-based recommendations and practical considerations for disclosures about placebo and nocebo effects in clinical practice. Future research is needed on how to optimally tailor information to specific clinical conditions and patients' needs, and on developing standardized disclosure training modules for clinicians.

Merely Possessing a Placebo Analgesic Improves Analgesia Similar to Using the Placebo Analgesic.

BACKGROUND: Placebo analgesia studies generally reported that the actual use of a placebo analgesic reduces pain. Yeung, Geers, and Kam found that the mere possession (without use) of a placebo analgesic also reduces pain. PURPOSE: We investigated the relative effectiveness of using versus possessing a placebo analgesic on pain outcomes. METHODS: In Study 1a, 120 healthy adults were randomized to either the experimental (EXP) conditions (EXP1: used a placebo analgesic cream, EXP2: possessed a placebo analgesic cream) or control (CO) conditions (CO1: possessed a sham cream, CO2: no cream). All participants underwent a cold pressor test (CPT). Study 1b further delineated the effect of possession from the effect of use. Sixty healthy adults were randomized to either the placebo-possession condition (merely possessed a placebo analgesic cream) or the placebo-possession-use condition (possessed and used a placebo analgesic cream). All participants did a CPT. RESULTS: In Study 1a, as expected, a placebo effect was found-participants who used a placebo analgesic cream showed better pain outcomes than the two CO groups. Surprisingly, participants who merely possessed a placebo analgesic cream performed equally well as those who actually used it. In Study 1b, participants in the two conditions did not differ in most pain outcomes. Participants who possessed and used a placebo analgesic cream only showed slightly more reduction in pain intensity compared to participants who merely possessed the placebo analgesic cream. CONCLUSIONS: Our results suggest that merely possessing a placebo analgesic could enhance pain outcomes similar to that of applying the placebo analgesic.

European Headache Federation recommendations for placebo and nocebo terminology.

BACKGROUND AND AIM: Despite recent publications, practitioners remain unfamiliar with the current terminology related to the placebo and nocebo phenomena observed in clinical trials and practice, nor with the factors that modulate them. To cover the gap, the European Headache Federation appointed a panel of experts to clarify the terms associated with the use of placebo in clinical trials. METHODS: The working group identified relevant questions and agreed upon recommendations. Because no data were required to answer the questions, the GRADE approach was not applicable, and thus only expert opinion was provided according to an amended Delphi method. The initial 12 topics for discussion were revised in the opinion of the majority of the panelists, and after a total of 6 rounds of negotiations, the final agreement is presented. RESULTS/RECOMMENDATIONS: Two primary and mechanism-based recommendations are provided for the results of clinical trials: [1] to distinguish the placebo or nocebo response from the placebo or nocebo effect; and [2] for any favorable outcome observed after placebo administration, the term "placebo response" should be used, and for any unfavorable outcome recorded after placebo administration, the term "nocebo response" should be used (12 out of 17 panelists agreed, 70.6% agreement). The placebo or nocebo responses are attributed to a set of factors including those that are related to the medical condition (e.g. natural history, random comorbidities, etc.), along with idiosyncratic ones, in which the placebo or nocebo effects are attributed to idiosyncratic, or nonspecific mechanisms, exclusively (e.g. expectation, conditioning, observational learning etc.). To help investigators and practitioners, the panel summarized a list of environmental factors and idiosyncratic dynamics modulating placebo and nocebo effects. Some of them are modifiable, and investigators or physicians need to know about them in order to modify these factors appropriately to improve treatment. One secondary recommendation addresses the use of the terms "placebo" and "nocebo" ("placebos" and "nocebos" in plural), which refer to the triggers of the placebo/nocebo effects or responses, respectively, and which are inert agents or interventions that should not be confused with the placebo/nocebo responses or effects themselves (all panelists agreed, 100% agreement). CONCLUSION: The working group recommends distinguishing the term response from effect to describe health changes from before to after placebo application and to distinguish the terms placebo(s) or nocebo(s) from the health consequences that they cause (placebo/nocebo responses or effects).

A Positive Mood Induction for Reducing the Formation of Nocebo Effects from Side Effect Information.

BACKGROUND: Providing treatment side effect information can increase the occurrence of side effects through nocebo effects. Nocebo effects from side effect information raise a dilemma for health care, as there is an ethical obligation to disclose potential unpleasant treatment information to patients. PURPOSE: To test the hypothesis that a positive mood induction can block the development of nocebo effects that result from treatment side effect information. METHODS: In a laboratory setting, healthy participants were assigned to one of four conditions in a between-subjects randomized factorial trial. First, participants took part in a mood induction procedure, with half receiving a positive mood induction and the other half a neutral mood induction. Next, participants were told they would experience transcranial direct current stimulation (tDCS). Prior to a sham tDCS task, half of the participants were informed that headache pain is a side effect of tDCS, whereas the other half were not given this information. RESULTS: In the neutral mood condition, the provision of headache side effect information lead to a greater occurrence of headaches, more frequent headaches, and a higher maximum level of headache pain as compared to those given no side effect information. In the positive mood condition, a similar increase in headache pain did not manifest from the provision of side effect information. CONCLUSIONS: This is the first experiment to find that a positive mood induction can block the formation of nocebo effects that arise from side effect information. Inducing positive moods may be an effective strategy for reducing nocebo effects in a variety of clinical settings.

The Influence of Side Effect Information Framing on Nocebo Effects.

BACKGROUND: One contributing factor to the development of nocebo effects is information provided about possible side effects. However, nondisclosure of information can be problematic. PURPOSE: We assessed whether positively framed side effect information (highlighting likelihood of not experiencing side effects) can reduce nocebo effects compared to negatively framed information (highlighting likelihood of experiencing side effects). METHODS: One hundred twelve participants took part in research ostensibly assessing the influence of benzodiazepines (actually sham capsules) on anxiety. Participants were randomized to receive a sham capsule with positively or negatively framed information about four side effects, or a no-treatment control condition. Side effect expectations were assessed after information provision. Framed side effects and other unmentioned symptoms were assessed during the session and 24-hr follow-up. RESULTS: Nocebo effects occurred in symptoms presented as side effects (regardless of framing) during the study session and follow-up (ps < .003). At follow-up, there was also a nocebo effect in other unmentioned symptoms (p = .018). Positive framing reduced side effect symptoms compared with negative framing during the study session (p = .037), but this effect was no longer present at follow-up (p = .53). Side effect expectations did not differ between the framing conditions (p = .14). CONCLUSIONS: Positive framing reduced side effects short-term, but not at follow-up. Expectations did not differ between negative and positive framing. Nocebo effects appeared to generalize to other unmentioned symptoms over a 24-hr period. Further research is needed to determine whether the initial impact of positive framing can be maintained over time.

Assessing the Relationship Between Implicit and Explicit Evaluations of Fruit and Vegetable Consumption by Cancer Survivors.

BACKGROUND: Currently, little is known about the implicit evaluations that cancer survivors have for health behaviors, such as eating fruits and vegetables. Understanding both the implicit and explicit evaluations of fruit and vegetable consumption among cancer survivors may aid future interventions for changing motivations and intentions in this higher risk population. METHODS: A cross-sectional study at a university cancer center assessed explicit and implicit evaluations of fruit and vegetable consumption among 122 cancer survivors. The explicit evaluations regarding fruit and vegetable consumption were self-report data. To obtain implicit evaluations, participants completed an implicit evaluation task, the Affect Misattribution Paradigm. Moderating variables of time since first cancer treatment and if participants had a prior cancer occurrence were also self-reported. RESULTS: Simple correlations found no significant association between the implicit and explicit evaluations of fruit and vegetable consumption. Moderation regression analyses showed that the implicit and explicit evaluations became negatively associated as time since first treatment increased and when participants had a prior cancer occurrence. CONCLUSION: The results support the view that implicit and explicit measures of fruit and vegetable consumption diverge for cancer survivors, consistent to implicit and explicit evaluations in other domains and samples. Further, the association between these evaluations differed depending on time since first treatment and if they have been treated for a prior cancer occurrence. By knowing more about implicit and explicit positive evaluations, and their moderators, it may be possible for interventionists to alter cancer survivors' motivation and intention to eat fruits and vegetables.

Too picky for my taste? The effect of the gluten-free dietary restriction on impressions of romantic partners.

Millions of individuals world-wide adhere to a gluten-free diet and this dietary trend is on the rise. The present research identified a consumption stereotype of those following a gluten-free diet and tested whether this stereotype influenced impressions and interest in a potential romantic partner. We also assessed whether being gluten-free differentially impacted impressions of males compared to females. In Study 1, participants (N = 161) responded to a survey containing both qualitative and quantitative components in which they evaluated gluten-free individuals and indicated their interest in dating them. In Study 2 (N = 132), we manipulated the dietary restriction (gluten-free vs. no dietary restriction) of a target within the context of a mock online dating paradigm and measured participants' evaluations of the target. In both studies, gluten-free individuals were perceived as having positive and negative attributes such as being high-maintenance, picky, demanding, complaining and judgmental, yet healthy, self-disciplined, understanding and energetic. The gluten-free diet was associated with ratings of femininity and lead to more negative judgments of males than females. Whereas in Study 1 participants expressed some hesitation about dating a gluten-free individual, no effects on romantic interest were obtained in Study 2. These data are the first to delineate the gluten-free stereotype and provide a useful platform for future study.

Implications of Placebo and Nocebo Effects for Clinical Practice: Expert Consensus.

BACKGROUND: Placebo and nocebo effects occur in clinical or laboratory medical contexts after administration of an inert treatment or as part of active treatments and are due to psychobiological mechanisms such as expectancies of the patient. Placebo and nocebo studies have evolved from predominantly methodological research into a far-reaching interdisciplinary field that is unravelling the neurobiological, behavioural and clinical underpinnings of these phenomena in a broad variety of medical conditions. As a consequence, there is an increasing demand from health professionals to develop expert recommendations about evidence-based and ethical use of placebo and nocebo effects for clinical practice. METHODS: A survey and interdisciplinary expert meeting by invitation was organized as part of the 1st Society for Interdisciplinary Placebo Studies (SIPS) conference in 2017. Twenty-nine internationally recognized placebo researchers participated. RESULTS: There was consensus that maximizing placebo effects and minimizing nocebo effects should lead to better treatment outcomes with fewer side effects. Experts particularly agreed on the importance of informing patients about placebo and nocebo effects and training health professionals in patient-clinician communication to maximize placebo and minimize nocebo effects. CONCLUSIONS: The current paper forms a first step towards developing evidence-based and ethical recommendations about the implications of placebo and nocebo research for medical practice, based on the current state of evidence and the consensus of experts. Future research might focus on how to implement these recommendations, including how to optimize conditions for educating patients about placebo and nocebo effects and providing training for the implementation in clinical practice.

Identifying when choice helps: clarifying the relationships between choice making, self-construal, and pain.

Prior research indicates that making choices before a painful task can sometimes reduce pain. We examined the possibility that independent and interdependent self-construals moderate the effect of choice on pain. Further, we tested between two types of choice: instrumental and non-instrumental. Healthy normotensive undergraduates were randomly assigned to one of three conditions prior to the cold pressor task. Participants in an instrumental choice condition selected which hand to immerse in the water and were told this choice might help reduce their pain. Non-instrumental choice participants selected which hand to immerse but were given no information about potential pain reduction. Control participants were given no choice or additional instructions. Low interdependence individuals reported less pain than high interdependence individuals-but only when given an instrumental choice. These data indicate that not all forms of choice reduce pain and not all individuals benefit from choice. Instead, individuals low in interdependence exhibit pain relief from instrumental choices.

Affect and exercise: positive affective expectations can increase post-exercise mood and exercise intentions.

BACKGROUND: Prior research has found affect to predict exercise. Little research has examined the causal influence of exercise-related affect on exercise intentions. PURPOSE: The purpose of this study was to test whether expectations about post-exercise affect can be successfully manipulated to produce changes in post-exercise affect and exercise intentions. We also tested whether cognitively elaborating on the expectation would increase the duration of the expectation effect. METHODS: Participants (59 men, 89 women) were exposed to an affective expectation manipulation as well as an elaboration manipulation and then completed 10 min of light-intensity exercise on a stationary bicycle in the laboratory. Participants also completed a 2-week follow-up. RESULTS: Affective expectation participants displayed more positive post-exercise affect and exercise intentions than no-expectation participants (ps < .05). Affective expectation participants who also elaborated on that expectation reported more positive post-exercise affect during the follow-up than the no-elaboration participants (p < .05). CONCLUSION: Expectations about positive post-exercise affect can be experimentally manipulated to increase exercise-related feelings and intentions. The duration of this effect increases when individuals cognitively elaborate on the expectation.

Prior experience with a pain stimulus as a predictor of placebo analgesia.

Placebo effects are important in pain reduction, but the effects are inconsistent. Prior experience with a pain stimulus may moderate placebo analgesia. The current study tests the effect of prior experience with a pain stimulus on placebo analgesia during a laboratory pain task. Healthy normotensive undergraduates (66 women, 68 men) who either did or did not report prior experience with pain from submerging a limb in cold water were enrolled. In the laboratory, an experimenter applied an inert, medicinal-smelling cream to participants' non-dominant hand. Participants randomized to the no-expectation group were told that the cream was a hand cleanser. Participants randomized to the placebo expectation group were told that the cream would reduce the pain associated with the cold pressor task. Participants then completed the cold pressor task and reported their pain on the short form of the McGill Pain Questionnaire. Analysis of variance revealed a main effect of expectation (p < .05), such that participants in the placebo expectation group reported less pain. An interaction was also found between expectation and prior experience (p < .05), such that participants with prior experience with pain from cold water immersion showed no difference in pain reports between expectation groups. In a pain context, prior experience with the pain stimulus may prevent a placebo expectation from reducing the experience of pain.

Norm perception and communication for vasovagal symptoms in blood donation.

BACKGROUND: Blood is a valuable resource, but most people do not donate. One deterrent to blood donation is the anticipation of vasovagal symptoms (e.g., dizziness, nausea, and fainting), despite the fact that such symptoms typically affect a small proportion of donors. The current research examined norm perceptions regarding vasovagal symptom experiences and used a message-framing paradigm to communicate accurate norm information and increase future donation intentions. STUDY DESIGN AND METHODS: Three studies were conducted using young adult samples. In Study 1, donors and nondonors estimated the percentage of people who experience vasovagal symptoms. In Studies 2 and 3, nondonors and donors (respectively) were provided with accurate, positively framed, or negatively framed norm messages and indicated their intentions to donate. RESULTS: In Study 1 we found that participants vastly overestimated how normative it was to experience vasovagal symptoms and this overestimation was stronger among nondonors. In Studies 2 and 3, we showed that positively framed normative messages ("90% of donors do not experience vasovagal symptoms") were generally more influential than negatively framed messages ("10% of donors do experience vasovagal symptoms"), except among past donors who had unfavorable donation experiences. CONCLUSION: These findings suggest that targeting and correcting norm perception may be a critical step toward improving blood donation rates.