Placebo Responding Research Articles

To respond or not to respond: exploring empathy-related psychological and structural brain differences between placebo analgesia responders and non-responders.

Placebo responsiveness is highly variable across individuals. In the domain of pain, it may range from pronounced hypoalgesia to no response at all. Which factors predict such variation awaits clarification, as the available literature is characterized by mixed and inconclusive results. Particularly interesting in this case are social factors such as empathy or prosocial behavior, as prior work has stressed the connection between feeling pain yourself and empathizing with pain observed in others. In a mixed confirmatory and exploratory approach, this study investigated potential psychological and structural brain differences between placebo responders and non-responders in the domain of pain. We aggregated data of four behavioral and neuroimaging studies that had been designed to investigate the effects of placebo analgesia on empathy. Analyses comparing groups of placebo responders and non-responders showed significant group differences in trait characteristics, with responders reporting increased helping behavior and lower psychopathic traits compared to non-responders. Uncorrected results further showed higher pain-related empathic concern in responders vs. non-responders. These results were accompaniedby tentative group differences in brain structure: placebo analgesia non-responders exhibited increased gray matter volume in left inferior temporal and parietal supramarginal cortical areas, and an increased cortical surface area in bilateral middle temporal cortex. Together, our findings suggest that modifiability of one's pain perception by means of placebo effects is linked to personality traits characterizing social emotions and behavior. They also hint that these psychological as well as brain structural characteristics might be beneficial for the identification of placebo responders. At the same time, they stress the importance of considering contextual factors such as the study setting or paradigm when investigating the association between individual characteristics and placebo responding.

Associations Between Interindividual Differences, Expectations and Placebo and Nocebo Effects in Itch.

Introduction: Placebo and nocebo effects are positive and negative health outcomes that can be elicited by the psychosocial context. They can be mediated by expectations, and may emerge in somatic symptoms even when people are aware of these effects. Interindividual differences (e.g., in personality, affective states) could impact placebo and nocebo responding, but findings are inconsistent.Methods: The current work examined expectation as a mediator of the association between verbal placebo and nocebo suggestions (VSs) and histamine-induced itch across three experimental studies. Moreover, we examined whether interindividual differences (e.g., in optimism, neuroticism, behavioral activation system (BAS), body ignorance) modulated: (1) the direct association between VSs and itch (direct moderation), and (2) the indirect, expectation-mediated association between VSs and itch (moderated mediation). Positive VSs were compared to neutral instructions (Study 1; n = 92) or negative VSs (Studies 2+3; n = 203) in an open-label (i.e., explaining placebo and nocebo effects) or closed-label (concealed) context using PROCESS. First, mediation of VSs effects on itch by expectations was tested. Next, moderation by individual traits was explored using conditional process analyses.Results: The effects of VSs on itch were significantly mediated by expectation in Study 1 and in the open-label (but not closed-label) contexts of Studies 2 and 3. Ignorance of bodily signals marginally moderated the direct effects of VSs on itch when closed-label suggestions were given: at low levels of body ignorance, effects of positive and negative VSs were stronger. Moreover, moderated mediation was observed in the open-label groups of Studies 2 and 3: The expectation-mediated effects of VSs on itch were stronger when BAS drive was lower.Conclusion: Overall, the effects of VSs on itch were mediated by expectations in the open-label, but not the closed-label context. Moreover, the current work suggests that placebo and nocebo effects may be moderated by ignorance of bodily signals and the BAS. There was limited evidence that other interindividual differences modulated placebo and nocebo responding in itch.

Direct Verbal Suggestibility as a Predictor of Placebo Hypoalgesia Responsiveness.

Reliably identifying good placebo responders has pronounced implications for basic research on, and clinical applications of, the placebo response. Multiple studies point to direct verbal suggestibility as a potentially valuable predictor of individual differences in placebo responsiveness, but previous research has produced conflicting results on this association. In two double-blind studies, we examined whether behavioral direct verbal suggestibility measures involving a correction for compliance would be associated with individual differences in responsiveness to conditioned and unconditioned placebo hypoalgesia using an established placebo analgesia paradigm. In study 1 (n = 57; mean [standard deviation] age = 23.7 [8.1] years; 77% women), we used behavioral hypnotic suggestibility as a predictor of placebo hypoalgesia induced through conditioning and verbal suggestion, whereas in study 2 (n = 78; mean [standard deviation] = 26.1 [7.4] years; 65% women), we measured nonhypnotic suggestibility and placebo hypoalgesia induced through verbal suggestion without conditioning. In study 1, the placebo hypoalgesia procedure yielded a moderate placebo response (g = 0.63 [95% confidence interval = 0.32 to 0.97]), but the response magnitude did not significantly correlate with hypnotic suggestibility (rs = 0.11 [-0.17 to 0.37]). In study 2, the placebo procedure did not yield a significant placebo response across the full sample (g = 0.11 [-0.11 to 0.33]), but the magnitude of individual placebo responsiveness significantly correlated with nonhypnotic suggestibility (rs = 0.27 [0.03 to 0.48]). These results suggest that the extent to which direct verbal suggestibility captures variability in placebo responsiveness depends on the use of conditioning and highlights the utility of suggestibility as a potential contributing factor to placebo responding when placebo hypoalgesia is induced through verbal suggestions.

0366 SUBJECTIVE-OBJECTIVE DISCREPANCIES IN TREATMENT OUTCOME WITH FOUR TYPES OF HYPNOTICS: A FIRST PASS ANALYSIS

Hypnotics may have different effects on subjective (sleep diary [SD]) and objective (PSG) measures of sleep continuity. Thus, the concurrent examination of both measurement strategies, while rarely done, is important because improvement in one domain may not be paralleled by improvement in the other domain. Meta-analytic data were used to assess the association of subjective and objective treatment outcomes by drug class. PubMed searches, from 1967-June 2016, yielded 327 possible articles of RCTs evaluating BZs, BZRAs, SADs, DORAs, or melatonin agonists (MELA). Weighted effect sizes (ES) were computed for the pre-post change data and were compared to the study placebo condition. Between measurement strategy differences were assessed using ES difference scores. Note: positive values favor sleep diary outcomes and negative values favor PSG outcomes. Sufficient data were available for only BZRAs, SADs, DORAs, and MELA. When examining subjective-objective ES difference scores the following was observed: SL (BZRAs = 0.04; SADs = 0.02; DORAs = -0.03; MELA = -0.14); WASO (MELA = 0.03; BZRAs = -0.01; DORAs = -0.17; SADs = -0.26); and TST (BZRAs = 0.03; SADs = -0.03; DORAs = -0.10; MELA = -0.11). These preliminary results indicate that, overall, BZRAs produce the most concordant results on PSG and self-report measures (when taking into account placebo responding). The most discordant results, overall, were found with the DORAs and MELA, although the single most discordant value was for SADs on WASO. In each of these cases, PSG measures were found to show greater levels of efficacy. Given that subjective and objective treatment gains may reflect different benefits to the patient, discordance need not be viewed as better or worse efficacy. This said, medications that disproportionately affect objective measures may not be viewed favorably by patients and this may, in turn, adversely affect treatment adherence. Partial support provided by R56AG050620 and R01AG041783.

Sources of Placebo-Induced Relief From Nausea: The Role of Instruction and Conditioning.

It is well documented that expectancies alter the nauseous response. However, the lack of integration in research examining sources of expectancy has limited our understanding of how expectancies are formed and, consequently, our ability to intervene. The present study explored the role of both instructions and conditioning in placebo-induced relief from nausea. The study used a 2 × 2 between-subjects design with instruction and conditioning as factors with 56 healthy volunteers. The instruction manipulation involved randomizing participants to receive information that a sham treatment (a peppermint essence vapor) would reduce nausea or no such instructions. The conditioning manipulation involved further randomizing participants to have the first administration of this sham treatment paired with a surreptitious reduction in galvanic vestibular stimulation (GVS) intensity or no prior pairing. Nausea was induced through GVS. On test, all groups received the same level of GVS with the sham treatment present. On test, participants who received instruction had significantly lower nauseous response scores than those who did not (F(1,46) = 6.71, p = .013), and those who received conditioning also reported less nausea than those who did not (F(1,46) = 5.20, p = .027), with the interaction between the two not reaching statistical significance (F(1,46) = 2.33, p = .13). These findings indicate that placebo responding in nausea can be induced both through positive instructions and as little as one pairing of a treatment with a reduction in nausea, as well as their combination. This suggests that using placebo effects to complement antiemetic therapy may offer an important method of further reducing nausea in the clinic.

‘Oxytocin’ for the outwardly oriented: Evidence for interactive effects in placebo responding

ObjectiveIn order to harness the placebo effect for clinical benefit, more research is needed to determine who might be responsive to a placebo treatment. Recently, a two-faceted Transactional Model of Placebo Responding (TMPR) was offered, which suggests different personality types might respond to different contextual cues. The current study directly tested this model by manipulating treatment descriptors to match the two purported facets of responsiveness. MethodsPhysically healthy volunteers (N=77) experiencing life stress were randomised to either the: (1) wait-list control, (2) ‘serotonin treatment’ group; or (3) ‘oxytocin treatment’ group. Both treatment groups received an ‘antistress’ intranasal spray (placebo). The ‘serotonin’ and ‘oxytocin’ treatments were described to appeal to the two purported facets responsiveness set out in the TMPR, inward and outward orientation. The BIS/BAS scale was used as proxies for inward (BIS) and outward (BAS) orientation. It was hypothesised that high BAS types would be more responsive to the ‘oxytocin’ and high BIS types would be more responsive to the ‘serotonin’. ResultsFindings provide partial support for hypotheses, with high but not low BAS types having a greater response to the ‘oxytocin’ placebo; but the pattern of responses from high BIS types were contrary to predictions. ConclusionsFindings indicate interactions between personality type and environmental cues may contribute to placebo responding, but more research is needed to investigate possible operationalisations of responsiveness and the contextual cues to which different types may respond.

Seeing is believing: Impact of social modeling on placebo and nocebo responding.

This study investigated the impact of the social modeling of side effects following placebo medication ingestion on the nocebo and placebo effect. It also investigated whether medication branding (brand or generic labeling) moderated social modeling effects. Eighty-two university students took part in the study which was purportedly investigating the impact of fast-acting beta-blocker medications (actually placebos) on preexamination anxiety. After taking the medication, participants were randomized to either witness a female confederate report experiencing side effects or no side effects after taking the same medication. Differences in symptom reporting, blood pressure, heart rate, and anxiety were assessed between the social modeling of side effects and no modeling groups. Seeing a female confederate report side effects reduced the placebo effect in systolic (p = .009) and diastolic blood pressure (p = .033). Seeing a female confederate report side effects also increased both total reported symptoms (mean [SE] 7.35 [.54] vs. 5.16 [0.53] p = .005) and symptoms attributed to the medication (5.27 [0.60] vs. 3.04 [0.59] p = .01), although the effect on symptoms was only seen in female participants. Females who saw the confederate report side effects reported approximately twice the number of symptoms as those in the no modeling group. Social modeling did not affect heart rate or anxiety. Medication branding did not influence placebo or nocebo outcomes. The social modeling of symptoms can substantially reduce or eliminate the placebo effect. Viewing a female confederate display symptoms after taking the same medication increases symptom reporting in females.

Understanding and translating the knowledge about placebo effects: the contribution of psychology.

Recent articles have summarized the literature on the neurobiological mechanisms involved in placebo effects. In this article, we review and evaluate the status of the psychological mechanisms in theory and research regarding placebo effects. Currently, the placebo effect literature concentrates more on neurobiological mechanisms than on psychological mechanisms. Both theoretical and empirical coverage of the psychological mechanisms are typically limited to two variables: conditioning and verbally induced expectations. Because psychological processes take center stage in mediating the link between the therapeutic context and placebo responding, greater effort is needed to build empirically derived and theoretically complex psychological process models. Such models would include a broader array of psychological constructs and mechanisms. Research and theory on placebo effects has illuminated much regarding the neurobiological mechanisms. The psychological mechanisms, however, have received much less attention. Expanding our knowledge regarding the psychological processes involved in placebo responding would open up opportunities for developing nondeceptive intervention techniques that encourage placebo responses. Ultimately, a concerted empirical effort to clarify the psychological model underlying placebo effects could merge with the evolving neurobiological model to fulfill the promise that placebo effects have for improving patient outcomes.

Who responds to placebos? Considering the “placebo personality” via a transactional model

The placebo effect is now recognised as a genuine psychobiological phenomenon; however, the question of how it can be systematically harnessed to improve health outcomes is not yet clear. One issue that remains unresolved is why some respond to placebos and others do not. A number of traits have been linked to responding, but findings are scattered. In extending prior work, this paper offers three considerations. First, attempts to describe the placebo responder via a single personality trait may be limiting. A synthesis of findings to date suggests placebo responsiveness may reflect a two-faceted construct, with “inward” and “outward” orientation representing the different but related facets of placebo responsiveness. Second, the lack of theoretically driven research may be hindering progress. Personality measures rather than personality theory appear to be driving research and higher order traits are descriptive tools with limited use in predicting behaviour. A biologically based stimulus–response model of personality that considers how individuals respond to certain environmental cues may be more appropriate. Third, a transactional model of placebo responding in which dispositional characteristics interact with environmental contingencies is presented. Responsiveness may manifest in placebo environments where there is a match between an individual’s biological trait-like response systems and environmental contingencies. This type of model may be useful in both research and clinical settings. Systematic consideration of how different individuals might respond to different placebo environments might facilitate identification of stable individual characteristics predictive of responding. The ability to determine who is responsive to placebo treatments, and in what context, may enable the matching of individual to treatment, thereby maximising the effectiveness of treatment and minimising possible iatrogenic harm. In the increasingly overtaxed modern health care industry, non-pharmacological treatment alternatives are of critical importance.

Motivation and expectancy influences in placebo responding: the mediating role of attention.

Drawing upon research in perception and motivation, the current study proposes a motivation-attention model of placebo in which more motivated persons pay greater attention to placebo-related stimuli, directly influencing placebo response. We manipulated both motivation to respond to placebo and expectations of placebo response in a 2 × 2 design. Participants (N = 152) evaluated a series of placebo pheromones (slightly scented water) of potential romantic dates and made desirability ratings. Consistent with hypotheses, more highly motivated participants demonstrated greater placebo responses, as evidenced by higher desirability ratings of the "pheromone" and greater variability among ratings, when compared to less motivated participants. Moreover, the relation between motivation and placebo response was mediated by attention. Contrary to expectations, we found no effect for expectancy. These findings highlight the importance of motivation and the mediating factor of attention in placebo and support goal-oriented models of placebo.

Psycho-Social Mediators of Placebo Effects

Placebo effects are dynamic and act synergistically with other therapeutic elements. Expectancy, Pavlovian conditioning, meaning effects, and therapeutic relationship are common mediators of placebo effects. In clinical situations, patients’ intensity for expectation of help is the main trigger of placebo response. Even physician expectations, belief, and empathy can produce placebo responsiveness in the patient. Ego development psychologists speculating on the mechanisms of placebo response see it as a rekindled soothing pattern of the early interaction with a care-giver projected as a healing symbol on the therapist. In the emotionally charged interactions in the doctor’s office, the prescriptions, pills, worksheets, and medical devices act as “transitional objects” mediating between the self and the world to promote patient’s sense of autonomy and self-efficacy. Psychoanalytic experts have stressed the healing power of positive transference in promoting placebo response by reduction of stress and anxiety and increasing positive emotions. Desire, belief, and expectancy combine to produce hope, which in itself is a potent mediator of the placebo effect. Hope can consciously or unconsciously motivate people to follow health-promoting behaviors and adhere to therapeutic regimens. The coronary drug project showed lower mortality even in the placebo-compliant group. Expectation also plays a major role in subjective and behavioral effects of the drugs acting on the central nervous system. Pharmacologically conditioned placebo responses mimic drug effects and can be used to decrease the dose and side effects of drugs in clinical practice. The psychosocial processes involved in placebo responding can apply to any treatment in the form of “embodied experience.” Personal suffering, when given a socially acceptable meaning, constitutes “meaning response,” which can be a wellspring of placebo effect. Therapeutic relationship is considered to be the most important component in promoting placebo effects. Physicians, by virtue of empathic communication; positive framing of the diagnosis; and a gentle, reassuring manner can transmit an impressive healing force in the treatment setting. The physical characteristics of the drugs sometimes account more than the chemical ingredients of the medication. These “meaning effects” are driven by unconscious symbolic images. Some important personality factors in eliciting placebo effects are: optimists respond better than pessimists, extroversion and openness helps, and acquiescing personalities are more likely to make use of others as a healing resource. Therapeutic relationship remains the most important progenitor of placebo effect, and incremental dose of quality and quantity time with a likable, empathic, reassuring doctor has been shown to produce a robust beneficial effect, even when no active treatment was employed.

Translating Geriatric Psychiatry Research into Practice: Coping with Uncertainty

-

Variability in placebo analgesia and the role of fear of pain—an ERP study

Fear of pain (FOP) and its effect on placebo analgesia was investigated. It was hypothesized that FOP should interfere with placebo-mediated pain inhibition and result in weaker placebo responding in pain intensity, pain unpleasantness, stress, and event-related potentials to contact heat pain. Thirty-three subjects participated in a balanced 2 condition (natural history, placebo)×3 test (pretest, posttest 1, posttest 2) within-subject design, tested on 2 separate days. FOP was measured by the Fear of Pain Questionnaire and subjective stress by the Short Adjective Check List. Placebo effects were found on reported pain unpleasantness and N2 and P2 amplitudes. FOP was related to reduced placebo responding in pain unpleasantness, but this was only evident for the subjects who received the placebo condition on day 1. Subjects who received the placebo condition on day 1 experienced more pretest stress than those who received the placebo condition on day 2 (ie, reversed condition order), and this explained the interaction effect on placebo responding. FOP was related to reduced placebo responding on P2 amplitude, whereas placebo responding on N2 amplitude was unaffected by FOP. Higher placebo responses on N2 and P2 amplitudes were both related to higher placebo analgesic magnitude in pain unpleasantness. In conclusion, increased FOP was found to reduce subjective and electrophysiological placebo analgesic responses.

Role of Central Neurophysiological Systems In Placebo Analgesia and Their Relationships With Cognitive Processes Mediating Placebo Responding

The harnessing of the positive aspects of the placebo effect in clinical practice is a major clinical and ethical challenge, and requires better understanding of placebo mechanisms. In this article, we present an explanatory cognitive model of placebo analgesia, centered on expectation of pain relief, and present direct and indirect evidence for the psychological and physiological drivers and downstream mediators of the effects of expectation on reduction in pain. The endogenous opioid system is involved in expectation-mediated analgesia, but it is not known whether this system is required for the generation or downstream effects of expectation. There is indirect evidence to support the role of other neurotransmitter systems, such as the serotonergic and dopamine systems, and a possible role of the hypothalamic–pituitary–adrenal stress axis. The future challenge is the identification of the causal role of these systems in placebo analgesia, which would provide an empirical basis for exploring new pain therapies.

Reinforcing effects of d-amphetamine

Progressive-ratio schedules are useful for studying the reinforcing effects of drugs. Earlier human laboratory studies showed that d-amphetamine significantly increased break points relative to placebo. However, the magnitude of the increase was modest, which may be attributable to rather high levels of placebo responding. We used novel response requirements in a modified progressive-ratio procedure and hypothesized that the altered range of response requirements would decrease responding for placebo and increase responding for d-amphetamine. Eight participants completed the study. The participants first sampled oral doses of d-amphetamine (0, 8, 16, and 24 mg). In subsequent sessions, the participants were offered the opportunity to work for the sampled dose on a modified progressive-ratio procedure with response requirements ranging from 400 to 1800 mouse clicks. A battery of participant-rated drug-effect questionnaires, a performance measure, and cardiovascular measures were included to more fully characterize the effects of d-amphetamine. Placebo maintained low levels of responding. The intermediate dose of d-amphetamine increased responding significantly above placebo levels. d-Amphetamine produced prototypical subject-rated effects that were an orderly function of dose. These data suggest that the modified response requirements resulted in lower levels of placebo taking and a larger separation between the number of placebo and d-amphetamine capsules earned.

Placebo expectations and the detection of somatic information.

In a laboratory study we examined the hypothesis that placebo expectations enhance the initial identification of placebo-relevant sensations over placebo-irrelevant sensations. Participants (N = 102) were randomly assigned to one of three expectation groups. In the first group, participants ingested a placebo capsule and were told it was caffeine (deceptive expectation). In a second group, participants ingested a placebo capsule and were told it may be caffeine or it may be a placebo (double-blind expectation). Participants in the third group were given no expectation. All participants then tallied the placebo-relevant and placebo-irrelevant sensations they experienced during a 7-min period. Participants in the deceptive expectation group identified more placebo-relevant sensations than placebo-irrelevant sensations. No-expectation participants identified more placebo-irrelevant sensations than placebo-relevant sensations. Participants given the double-blind expectation identified an equal amount of placebo-relevant and irrelevant sensations. The amount of both placebo-relevant and placebo-irrelevant sensations detected mediated the relationship between the expectation manipulation and subsequent symptom reports. These data support the position that expectations cause placebo responding, in part, by altering how one identifies bodily sensations.

Dispositional optimism predicts placebo analgesia.

Based on prior research identifying dispositional optimism as a predictor of placebo responding, the present study tested the hypothesis that individuals high in optimism would be more likely to respond to a placebo analgesic. Optimists and pessimists were randomly assigned to a placebo expectation condition or a no expectation condition before a cold pressor task. Blood pressure and heart rate were recorded before and during the cold pressor task, and participant ratings of pain and expectations were obtained immediately after the task. Analysis of the expectation manipulation revealed that the placebo instruction was successful in altering participant expectancy during the cold pressor. Supporting the main hypothesis, dispositional optimism was associated with lower pain ratings in the placebo condition but not in the control condition. Because dispositional optimism can alter placebo responding to laboratory pain, future studies should examine the potential role that this individual difference factor may play in patient responsivity to pharmacological and nonpharmacological treatments for clinical pain. This study examined the possibility that individual differences can predict placebo analgesia. Participants were randomly assigned to receive either a placebo expectation or no expectation before a cold pressor task. Dispositional optimism was related to less cold pressor pain in the placebo condition as compared with the control condition.

Response expectancies: a psychological mechanism of suggested and placebo analgesia

AbstractResponse expectancies, or the expectation of one's own non‐volitional reactions to situational cues, are hypothesized to be a psychological mechanism of both hypnotic and placebo responding (Kirsch, 1990). In this study, response expectancies were evaluated as a mediator of suggested and placebo analgesia using Baron and Kenny's (1986) classic method of testing mediation. One hundred and seventy‐two volunteers were randomly assigned to hypnotic analgesia suggestion, imaginative analgesia suggestion, placebo analgesia, or no‐treatment control conditions. The hypnotic, imaginative and placebo treatments were more effective than the no‐treatment control condition in relieving finger pressure pain. The hypnotic treatment was also more effective than the placebo. Each of the three treatments was partially mediated by response expectancies, although the percentage of mediation varied across the hypnotic (25%), imaginative (29%) and placebo (41%) conditions. The findings support the position that response expectancies are one of the major psychological mechanisms of suggested and placebo analgesia. Copyright © 2009 British Society of Experimental & Clinical Hypnosis. Published by John Wiley & Sons, Ltd.

Further evidence for individual differences in placebo responding: An interactionist perspective

Objective A prior investigation found that individuals low in optimism are more likely to follow a negative placebo (nocebo) expectation. The present study tested the hypothesis that individuals high in optimism are more likely to follow a positive placebo expectation. Methods Individuals ( N=56) varying in their level of optimism were randomly assigned to one of three conditions. In the first condition, participants were given the expectation that a placebo sleep treatment would improve their sleep quality (placebo expectation condition). In the second condition, participants engaged in the same sleep treatment activity but were not given the positive placebo expectation (treatment control condition). Finally, a third group did not receive the positive placebo expectation and also did not engage in the placebo sleep treatment (no-placebo control condition). Results Optimism was positively associated with better sleep quality in the placebo expectation condition ( r=.48, P<.05). Optimism scores were not associated with better sleep quality in either the treatment control condition ( r=−.17, P=.46) or the no-placebo control condition ( r=−.24, P=.35). Conclusion Dispositional optimism relates to placebo responding. This relationship, however, is not manifested in a simple increase or decrease in all types of placebo responding. Rather, it appears that, as optimism increases, response to the positive placebo expectation increases, whereas response to nocebo expectation decreases. It is recommended that future research on personality and placebo effects consider the interaction between situational and dispositional variables.

Revelation of a personal placebo response: Its effects on mood, attitudes and future placebo responding

While ethics of placebo use has been debated since discovery of the phenomena, there has yet to be a study that examines the aftereffect of individuals learning of a personal placebo response on their future ability to experience a placebo response. In the first study, eleven participants diagnosed with irritable bowel syndrome in a placebo study were interviewed individually about their personal placebo response. We found no changes in attitudes about the likelihood of using medical and non-medical treatments for pain, likelihood of participating in future studies or likeability and trust of experimenters. In addition, we found no changes in mood except for a slight improvement in frustration. In the second study, 77 undergraduate students from the University of Florida were divided into three conditions: placebo, control and repeated baseline. We used a double placebo design with verbal placebo suggestion and conditioning to induce a placebo response and to examine the effect of providing information about a participant’s personal placebo response on their future placebo response. Using a heat thermode, we discovered that there were no differences in future pain responding between participants who were told that they experienced a placebo response versus those who were not. In addition, similar to the first study, we found no detrimental effects of the placebo information variables measured. These studies suggest the placebo response persists even after revelation of a personal placebo response and placebo use does not appear to cause adverse effects on mood and other attitude variables assessed.