Socially Acquired Nocebo Effects Generalize but Are Not Attenuated by Choice.

BACKGROUND: Socially observing a negative treatment-related experience has been shown to modulate our own experience with the same intervention, leading to worsened health outcomes. However, whether this social learning generalizes to similar but distinct interventions has not been explored nor what manipulations can reduce these effects. PURPOSE: To determine whether socially acquired nocebo effects can be generated by observing a negative experience with a similar, but distinct intervention, and whether choice can reduce these effects. METHODS: Across three experiments, a community sample of healthy adults (N = 336) either watched a confederate report cybersickness to the same Virtual Reality (VR) activity they were assigned to (Social Modeling: Consistent); a similar, but different VR activity (Social Modeling: Inconsistent); or did not view the confederate (No Social Modeling). Participants were either given choice over the VR (Choice) or assigned by the experimenter (No Choice). RESULTS: Across the experiments, there was significantly greater cybersickness in both Social Modeling groups relative to No Social Modeling, while the two Social Modeling groups did not differ. There was no significant effect of Choice or a Choice by Social Modeling interaction. Social Modeling elicited greater anxiety and expectancies for cybersickness. Furthermore, these mechanisms mediated the association between social modeling and cybersickness. CONCLUSIONS: Socially acquired side-effects were demonstrated to generalize to similar, but distinct interventions, highlighting the diffuse and robust effect social modeling can have on our experiences. However, choice did not attenuate the experience of cybersickness, highlighting the need for alternative methods to counteract the effect of social modeling.

Witnessing someone experience cybersickness during Virtual Reality (VR) generated a nocebo effect in the observer, exacerbating their own symptoms when subsequently encountering VR. The nocebo effect was not specific to the VR activity witnessed, but generalized across different VR experiences, demonstrating that socially acquired nocebo effects are likely to spread rapidly. Choice of VR environment did not reduce the nocebo effect elicited in the observer.

Peer-to-peer: The Social Transmission of Symptoms Online.

BACKGROUND: Social learning can be highly adaptive-for example, avoiding a hotplate your friend just burnt themselves on-but it has also been implicated in symptom transmission. Social learning is particularly pertinent given the rapid increase in the use of online mediums for social interaction. Yet, little is known about the social transmission of symptoms online or social chains extending further than a single model-observer interaction. PURPOSE: To explore whether socially induced symptoms could be propagated through a three-generation social transmission chain in an online setting. METHODS: We explored the social transmission of cybersickness following a virtual reality (VR) experience through online webcam interactions. One hundred and seventy-seven adults viewed a VR video in one of four links along a social transmission chain, after: viewing an actor model cybersickness to the VR video (First-Generation); viewing the First-Generation participant undergo VR (Second-Generation); viewing the Second-Generation participant undergo VR (Third-Generation); or naïve (Control). RESULTS: Cybersickness was strongest in First-Generation participants, indicating social transmission from the model. This was mediated by expectancy and anxiety. Whether or not subsequent generations experienced cybersickness depended on what the observed participant verbally reported, which is consistent with social transmission. CONCLUSIONS: Results demonstrate that symptoms can be readily transmitted online, and that expectancy and anxiety are involved. Although it is inconclusive as to whether symptoms can propagate along a social transmission chain, there is some evidence of protection from symptoms when a model who does not report any symptoms is observed. As such, this research highlights the role of social transmission in the modulation of symptoms through virtual mediums.

Social learning is a ubiquitous cognitive process whereby our own behaviors and experiences are influenced by observing others. Occasionally, this can involve the observation of an individual experiencing negative outcomes (e.g., pain or symptoms) following exposure to a treatment or intervention (e.g., consumption of medicine). Previous research has found that individuals may experience an increase in symptoms due to this social learning, even when their treatment has no active components. While research has primarily explored situations in which there is one model and one observer, it was of interest as to whether these socially induced symptoms can be transmitted beyond the first observer. Moreover, with social interaction through online mediums such as social media and video conferencing becoming more common, it was also of interest as to whether these symptoms can be transmitted online. The present findings highlight the significant role of social learning in symptom transmission, even when interactions occur online. With expectancy and anxiety being key features of this social transmission, this study highlights important implications for understanding how individuals can learn about their own future experiences through the observation of others.

Replication crisis and placebo studies: rebooting the bioethical debate.

A growing body of cross-cultural survey research shows high percentages of clinicians report using placebos in clinical settings. One motivation for clinicians using placebos is to help patients by capitalising on the placebo effect's reported health benefits. This is not surprising, given that placebo studies are burgeoning, with increasing calls by researchers to ethically harness placebo effects among patients. These calls propose placebos/placebo effects offer clinically significant benefits to patients. In this paper, we argue many findings in this highly cited and 'hot' field have not been independently replicated. Evaluating the ethicality of placebo use in clinical practice involves first understanding whether placebos are efficacious clinically. Therefore, it is crucial to consider placebo research in the context of the replication crisis and what can be learnt to advance evidence-based knowledge of placebos/placebo effects and their clinical relevance (or lack thereof). In doing so, our goal in this paper is to motivate both increased awareness of replication issues and to help pave the way for advances in scientific research in the field of placebo studies to better inform ethical evidence-based practice. We argue that, only by developing a rigorous evidence base can we better understand how, if at all, placebos/placebo effects can be harnessed ethically in clinical settings.

Choice and the Placebo Effect: A Meta-analysis.

BACKGROUND: Choice has been proposed as a method of enhancing placebo effects. However, there have been no attempts to systematically evaluate the magnitude, reliability, and moderators of the influence of choice on the placebo effect. PURPOSE: To estimate the effect size of choice on the placebo effect and identify any moderators of this effect. METHODS: Web of Science, PsycINFO, EMBASE, and PubMed were systematically searched from inception to May 2021 for studies comparing placebo treatment with any form of choice over its administration (e.g., type, timing) to placebo treatment without choice, on any health-related outcome. Random-effects meta-analysis was then used to estimate the effect size associated with the influence of choice on the placebo effect. Meta-regression was subsequently employed to determine the moderating effect of factors such as type of choice, frequency of choice, and size of the placebo effect without choice. RESULTS: Fifteen independent studies (N = 1,506) assessing a range of conditions, including pain, discomfort, sleep difficulty, and anxiety, met inclusion criteria. Meta-analysis revealed that choice did significantly enhance the placebo effect (Hedges' g = 0.298). Size of the placebo effect without choice was the only reliable moderator of this effect, whereby a greater effect of choice was associated with smaller placebo effects without choice. CONCLUSIONS: Treatment choice can effectively facilitate the placebo effect, but this effect appears more pronounced in contexts where the placebo effect without choice is weaker. Because most evidence to date is experimental, translational studies are needed to test whether providing choice in clinical scenarios where placebo effects are weaker may help boost the placebo effect and thereby improve patient outcomes.

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.

Mindfulness-Based Analgesia or Placebo Effect? The Development and Evaluation of a Sham Mindfulness Intervention for Acute Experimental Pain.

OBJECTIVE: Meta-analyses indicate that mindfulness meditation is efficacious for chronic and acute pain, but most available studies lack active control comparisons. This raises the possibility that placebo-related processes may account, at least in part, for mindfulness effects. The objective of this study was to develop a closely matched sham mindfulness condition to establish whether placebo effects contribute to mindfulness-based interventions for pain. METHODS: We developed and validated a closely matched sham mindfulness intervention then compared it with 6 × 20-minute sessions of focused-attention mindfulness and a no-treatment condition in 93 healthy volunteers undergoing acute experimental heat pain. RESULTS: The sham mindfulness intervention produced equivalent credibility ratings and expectations of improvement as the mindfulness intervention but did not influence mindfulness-related processes. In contrast, mindfulness increased "observing" relative to no treatment but not sham. Mindfulness (F(1,88) = 7.06, p = .009, ηp2 = 0.07) and sham (F(1,88) = 6.47, p = .012, ηp2 = 0.07) moderately increased pain tolerance relative to no treatment, with no difference between mindfulness and sham (F(1,88) = 0.01, p = .92, ηp2 < 0.001). No differences were found for pain threshold. Similarly, neither mindfulness nor sham reduced pain intensity or unpleasantness relative to no treatment, although mindfulness reduced pain unpleasantness relative to sham (F(1,88) = 5.03, p = .027, ηp2 = 0.05). CONCLUSIONS: These results suggest that placebo effects contribute to changes in pain tolerance after mindfulness training, with limited evidence of specific effects of mindfulness training on pain unpleasantness relative to sham, but not no treatment. To disentangle the specific analgesic effects of mindfulness from placebo-related processes, future research should prioritize developing and incorporating closely matched sham conditions.Trial Registration: Australian New Zealand Clinical Trials Registry (ACTRN12618001175268).

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.

Choice, Expectations, and the Placebo Effect for Sleep Difficulty.

BACKGROUND: Choice has been found to facilitate placebo effects for single-session treatments where standard placebo treatment without choice failed to elicit a placebo effect. However, it is unknown whether choice can enhance the placebo effect for treatments occurring over a period of days and where placebo effects are readily established without choice. PURPOSE: We tested whether single or daily choice between two (placebo) treatments enhanced the placebo effect for sleep difficulty relative to no choice and no treatment over a 1 week period. METHODS: One-hundred and seventeen volunteers self-identifying with sleep difficulty were recruited under the guise of a hypnotic trial and randomized to one of the four groups. Self-reported outcomes included insomnia severity, fatigue, total sleep time (TST), sleep onset latency (SOL), perceived sleep quality (PSQ), and treatment satisfaction. Objective TST and SOL were assessed in a subsample via actigraphy. RESULTS: Overall, placebo treatment significantly improved insomnia severity, fatigue, and PSQ, confirming a placebo effect on these outcomes. However, both traditional and Bayesian analysis indicated no benefit of choice on the placebo effect on any sleep outcome. Mediation analysis of the overall placebo effect indicated that expectancy completely mediated the placebo effects for insomnia severity and PSQ and partially mediated the placebo effect for fatigue. CONCLUSION: These findings suggest that choice does not enhance the placebo effect over longer treatment periods (up to 7 days) when placebo effects are readily established without choice. As such, any benefit of choice on placebo effects may be confined to quite specific circumstances. CLINICAL TRIALS REGISTRATION: ACTRN12618001199202.

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.

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.

Will human-like machines make human-like mistakes?

Although we agree with Lake et al.'s central argument, there are numerous flaws in the way people use causal models. Our models are often incorrect, resistant to correction, and applied inappropriately to new situations. These deficiencies are pervasive and have real-world consequences. Developers of machines with similar capacities should proceed with caution.

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

OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Effect of acupuncture and instruction on physiological recovery from maximal exercise: a balanced-placebo controlled trial.

BACKGROUND: This study aimed to investigate the effect of acupuncture administered immediately following a graded exercise test (GXT) on physiological measures of recovery and determine if instruction (expectancy) affected the responses. METHODS: A balanced-placebo 2 × 2 factorial design was used with treatment (real vs placebo acupuncture) and instruction (told real vs told placebo acupuncture) as factors; a no-treatment control group was also included to compare the treatment responses to no treatment. Recreationally active, acupuncture naïve young adults (n = 60) performed a GXT to exhaustion on a cycle ergometer (15 W/min). Heart rate, blood pressure, oxygen consumption, respiratory rate and blood lactate were collected during the test and during 60 min of supine recovery on a plinth. An experienced acupuncturist delivered real or placebo acupuncture within 6 min of completing the GXT (total treatment time = 20 min). Real acupuncture points included Neiguan (PC6), Zusanli (ST36), Lieque (LU7), and Tanzhang (REN17), while placebo acupuncture was delivered using the Park sham needle placed 1-2 cm away from each real acupuncture point. The control group received no intervention. RESULTS: Linear and quadratic trend analyses over time indicated no significant differences between groups on any dependent variable. However, analysis of specific timepoints (every 10 min of the 60 min recovery) revealed that participants who received some form of treatment had a lower heart rate than participants in the no treatment control group (p = 0.042) at 20 min post-exercise. Further, a significant treatment by instruction interaction effect for heart rate was also found at 50 min (p = 0.042) and 60 min (p = 0.013) post-exercise, indicating that the differences between real and placebo acupuncture were affected by expectancy manipulation. No other significant effects were noted. However, it was interesting to note that participants who believed they were given real acupuncture reported quicker perceived recovery independent of actual treatment (p = 0.006) suggesting that instruction about treatment influenced perceived recovery. CONCLUSION: In summary, due to limited evidence, the current study does not support the acute use of acupuncture for exercise recovery. However, importantly, the current study demonstrates that a balanced-placebo design is viable for testing acupuncture and expectancy effects, and this methodology could therefore be implemented in future studies. TRIAL REGISTRATION: ACTRN12612001015831 (Date registered: 20/09/2012).

Placebo interventions for nausea: a systematic review.

BACKGROUND: Expectancy often predicts nausea, but the extent to which placebo interventions can alter nausea is less clear. PURPOSE: We conducted a systematic review to determine 1) if placebo interventions can affect nausea and 2) which features of these interventions are effective. METHODS: Articles were identified via PsychInfo, Medline, and PubMed databases. We targeted instructional and conditioning interventions aimed at altering nausea via the placebo effect. RESULTS: Fourteen studies were identified, nine instructional and five conditioning. Many found evidence suggesting that placebo interventions could alter nausea, but a few found no evidence or 'reverse' effects. Effective interventions tended to be those that were aimed at participants with high initial expectancies, with evidence that combined or conditioning manipulations were more effective than instructions. CONCLUSIONS: These findings suggest that placebo interventions can alter nausea and that these may serve as a useful way of reducing the burden of nausea in practice.

The placebo effect, sleep difficulty, and side effects: a balanced placebo model.

Medical treatment is usually accompanied by a warning about potential side effects. While constituting an important component of informed consent, these warnings may themselves contribute to side effects via the placebo effect. We tested this possibility using a 2 × 2 between-subjects design. Under the guise of a trial of a new hypnotic, 91 undergraduates experiencing difficulty sleeping were allocated to receive a warning about a target side effect (either increase or decrease in appetite, counterbalanced) or no warning and then to receive placebo treatment or no treatment for one week. Placebo treatment led to significantly better sleep on almost all self-reported outcomes, suggesting a placebo effect for reported sleep difficulty. Actigraphy recordings were unaffected by treatment. There was a clear effect of the warning in that placebo treated participants who were warned about side effects were much more likely to report the target side effect than those not warned about side effects. Implications for clinical practice are discussed.

How food cues can enhance and inhibit motivation to obtain and consume food.

Learning may play an important role in over-eating. One example is Pavlovian-to-instrumental transfer (PIT), whereby reward cues facilitate responding to obtain that reward. Whilst there is increasing research indicating PIT for food in humans, these studies have exclusively tested PIT under instrumental extinction (i.e. when the food is no longer available), which may reduce their ecological validity. To address this, we conducted two experiments exploring PIT for food in humans when tested under instrumental reinforcement. Participants first underwent Pavlovian discrimination training with an auditory cue paired with a chocolate reward (CS+) and another auditory cue unpaired (CS-). In instrumental training participants learnt to press a button to receive the chocolate reward on a VR10 schedule. In the test phase, each CS was presented whilst participants maintained the opportunity to press the button to receive chocolate. In Experiment 1, the PIT test was implemented after up to 20 min of instrumental training (satiation) whereas in Experiment 2 it was implemented after only 4 min of instrumental training. In both experiments there was evidence for differential PIT, but the pattern differed according to the rate of responding at the time of the PIT test. In low baseline responders the CS+ facilitated both button press responding and consumption, whereas in high baseline responders the CS- suppressed responding. These findings suggest that both excitatory and inhibitory associations may be learnt during PIT training and that the expression of these associations depends on motivation levels at the time the cues are encountered. Particularly concerning is that a food-paired cue can elicit increased motivation to obtain and consume food even when the participant is highly satiated and no longer actively seeking food, as this may be one mechanism by which over-consumption is maintained.