Experience with opioids does not modify the brain network involved in expectations of placebo analgesia.

Placebo analgesia (PA) is defined as a psychobiological phenomenon triggered by the information surrounding an analgesic drug instead of its inherent pharmacological properties. PA is hypothesized to be formed through either verbal suggestions or conditioning. The present study aims at disentangling the neural correlates of expectations effects with or without conditioning through prior experience using the model of PA. We addressed this question by recruiting two groups of individuals holding comparable verbally-induced expectations regarding morphine analgesia but either (i) with or (ii) without prior experience with opioids. We then contrasted the two groups' neurocognitive response to acute heat-pain induction following the injection of sham morphine using electroencephalography (EEG). Topographic ERP analyses of the N2 and P2 pain evoked potential components allowed to test the hypothesis that PA involves distinct neural networks when induced by expectations with or without prior experience. First, we confirmed that the two groups showed corresponding expectations of morphine analgesia (Hedges' gs < .4 positive control criteria, gs = .37 observed difference), and that our intervention induced a medium-sized PA (Hedges' gav ≥ .5 positive control, gav = .6 observed PA). We then tested our hypothesis on the recruitment of different PA-associated brain networks in individuals with versus without prior experience with opioids and found no evidence for a topographic N2 and P2 ERP components difference between the two groups. Our results thus suggest that in the presence of verbally-induced expectations, modifications in the PA-associated brain activity by conditioning are either absent or very small.

Greater than the sum of the parts: a qualitative content analysis of what constitutes a good treatment in the inpatient setting.

BACKGROUND: The evaluation of psychotherapy is guided by established concepts, such as efficacy and effectiveness, and acceptability. Although these concepts serve as valid proxies, little is known about corresponding criteria for those directly involved in this treatment. This study aimed to explore inpatients' and health professionals' definitions of a good treatment in the inpatient setting. METHODS: Fifteen semi-structured interviews were conducted in a private psychiatric clinic in Switzerland and structured by qualitative content analysis. Different subsamples of the inpatient setting (patients N = 5; psychiatrists N = 5; other health professionals N = 5) were interviewed. RESULTS: In total, 546 text passages were grouped in 10 superordinate categories and identified as relevant for the concept of a good treatment. Participants stressed patient-specific (i.e., new insights; basic attitudes), treatment-specific (i.e., therapy methods and expertise; treatment success; therapy setting), and relationship-based (i.e., communication and feedback; relationships within the clinical setting; overcoming challenges and hurdles) components that are indispensable for a good therapeutic process. Components that are related to the clinical inpatient setting (i.e., setting and organization of the clinic; code of conduct) were also highlighted. CONCLUSIONS: Patients' and health professionals' definitions of what constitutes a good treatment entails a wide array of aspects. The clinical setting is seen to offer unique components that are emphasized to have a healing effect.

Comparative efficacy and acceptability of expressive writing treatments compared with psychotherapy, other writing treatments, and waiting list control for adult trauma survivors: a systematic review and network meta-analysis.

BACKGROUND: Expressive writing about a traumatic event is promising in treating posttraumatic stress disorder (PTSD) symptoms in adult trauma survivors. To date, the comparative efficacy and acceptability of this approach is uncertain. Therefore, we aimed to examine the comparative efficacy and acceptability of expressive writing treatments. METHODS: We included 44 RCTs with 7724 participants contributing 54 direct comparisons between expressive writing (EW), enhanced writing (i.e. including additional therapist contact or individualized writing assignments; EW+), PTSD psychotherapies (PT), neutral writing (NW), and waiting-list control (WL). RESULTS: EW, EW+, PT, and NW were statistically significantly more efficacious than WL at the longest available follow-up, with SMDs (95% CI) of -0.78 (-1.10 to -0.46) for PT, -0.81 (-1.02 to -0.61) for EW+ , -0.43 (-0.65 to -0.21) for EW, and -0.37 (-0.61 to -0.14) for NW. We found small to moderate differences between the active treatments. At baseline mean PTSD severity was significantly lower in EW+ compared with WL. We found considerable heterogeneity and inconsistency and we found elevated risk of bias in at least one of the bias dimensions in all studies. When EW+-WL comparisons were excluded from the analyses EW+ was no longer superior compared with EW. CONCLUSIONS: The summarized evidence confirms that writing treatments may contribute to improving PTSD symptoms in medium to long-term. Methodological issues in the available evidence hamper definite conclusions regarding the comparative efficacy and acceptability of writing treatments. Adequately sized comparative randomized controlled trials preferably including all four active treatment approaches, reporting long-term data, and including researchers with balanced preferences are needed.

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.

Informed consent in psychotherapy: a survey on attitudes among psychotherapists in Switzerland.

BACKGROUND: The legal and ethical guidelines of psychological professional associations stipulate that informed consent by patients is an essential prerequisite for psychotherapy. Despite this awareness of the importance of informed consent, there is little empirical evidence on what psychotherapists' attitudes towards informed consent are and how informed consent is implemented in psychotherapeutic practice. METHODS: 155 psychotherapists in Switzerland completed an online survey assessing their attitudes regarding informed consent. RESULTS: Among the surveyed psychotherapists, there was a high consensus on important information that should be communicated to patients in the context of informed consent. Almost all psychotherapists rated confidentiality and its exemptions (95%) and self-determined decision-making (97%) as important. The importance to disclose information regarding fees and the empirical effectiveness of the provided treatment, were both seen as important by more than 80% of participants. The disclosure of personal information about the therapist was rated as important by 60%. Other aspects, which are not direct components of informed consent but rather overarching goals, were also evaluated rather homogeneously: self-determined decision making of the patient was rated as important by almost all of the surveyed psychotherapists (97%). The following components were also judged as important by a majority of the participants: promotion of hope (80%) and discussion of treatment goals (93%). Most psychotherapists described the implementation of informed consent as an ongoing process, rather than a one-time event during the first session of therapy. Therapists' age, postgraduate training, treated patient group, and setting influenced attitudes towards informed consent. CONCLUSIONS: The present study shows that informed consent is perceived by psychotherapists as both a challenge and a resource. The implementation of informed consent in psychotherapy requires further research from a clinical and ethical perspective.

Vulnerable narcissism as beneficial factor for the therapeutic alliance in borderline personality disorder.

Evidence suggests that narcissism and borderline personality disorder are associated with each other. This naturalistic study investigated the predictive value of grandiose and vulnerable narcissism on the development of the therapeutic alliance in short-term psychodynamic treatment across 12 weeks. The sample consisted of 99 patients with borderline personality disorder. Narcissism was assessed with the Pathological Narcissism Inventory at treatment onset. The therapeutic alliance was rated with the Scale to Assess Therapeutic Relationships by both patient and therapist at four time points during treatment. Results showed a significant predictive value of vulnerable narcissism on the therapeutic alliance, revealing a more beneficial progression for patients with higher vulnerable narcissism. Grandiose narcissism had no predictive value on the therapeutic alliance. The study strengthens the clinical utility of the concept of vulnerable narcissism towards the evaluation of treatment processes in borderline personality disorder.

Effects of cognitive-behavioral stress management training in individuals with functional somatic symptoms - an exploratory randomized controlled trial.

Stress is discussed as a risk factor in the manifestation and maintenance of functional somatic (FS) symptoms. However, there is a lack of evidence regarding the effects of cognitive-behavioral stress management training (CBSM) on FS symptoms and the (potentially mediating) role of the neuroendocrine system. This study aims to examine stress-related psychological and neuroendocrine changes after receiving a brief CBSM in individuals with FS symptoms. Forty-three participants of both sexes, who reported at least one current FS symptom, were analyzed (treatment group (TG) n = 21, waitlist control group (WCG) n = 22) using mixed models. Number of symptoms, psychological stress, and salivary cortisol levels were assessed at pretreatment, posttreatment, and 6 months later. Mixed model analyses did not reveal significant differences between the TG and the WCG regarding number of FS symptoms (p > 0.05), psychological stress measures (p > 0.05) or the cortisol awakening response (CAR) (p > 0.05). The TG presented lower diurnal cortisol levels at pretreatment, posttreatment and 6 months later (p < 0.05). We did not find significant beneficial effects that were specific to CBSM. Further research should be undertaken to investigate the effects of CBSM on real life stress or laboratory stressors in subjects with FS symptoms. Moreover, learning cognitive restructuring and establishing new coping strategies into everyday life might require more time. This study is a first step in filling the gap in understanding the influences of CBSM as a brief intervention on psychological and biological aspects of stress in participants with FS symptoms and will hopefully inform larger trials of CBSM for FS symptoms.

Psychobiological impact of speaking a second language in healthy young men.

The use of second languages is ubiquitous in modern societies. Despite many benefits, there is also evidence for this to cause or exacerbate stress (e.g. in the form of foreign language anxiety). The aim of the present study was to examine to which extent speaking a second language increases acute psychobiological stress in a social context. A total of N = 63 healthy Swiss males were randomly allocated to one of two conditions: completing the Trier Social Stress Test (TSST) in Swiss German (their first language) vs. standard German (perceived as a second language). Repeated measures of self-reported stress, anxiety, salivary cortisol, and heart rate were obtained. Participants speaking standard German showed significantly larger cortisol increases in response to the TSST when compared to those speaking Swiss German (F(1, 61) = 5.53, p = .022, eta2 = .083). The two groups did not differ in terms of self-reported stress and anxiety, nor in their heart rate response (all p > .216). This study provides initial evidence that speaking a second language in social contexts increases the cortisol stress response. Future research should explore the short- and long-term effects this may have in populations frequently using second languages (e.g. learners of a second language, migrants).

Oncologist recommendation matters!-Predictors of psycho-oncological service uptake in oncology outpatients.

OBJECTIVE: Highly distressed cancer patients often do not use psycho-oncological services (POS). Research on predictors of POS uptake has mainly focused on patient-related variables and less on communication variables, so we examined the link between patient-oncologist communication (ie, talking about psychosocial distress, providing detailed information, and recommending POS) and POS uptake. METHODS: We conducted a prospective, observational study in an Oncology Outpatient Clinic in Switzerland. Predictors (ie, patient-related variables and patient's reports of the patient-oncologist communication) were assessed via semistructured interviews, and information on outpatient POS uptake was assessed after 4 months. For statistical analysis, a multivariate logistic regression was performed. RESULTS: Of 333 participants (mean age 61 years; 55% male; 54% distress thermometer ≥5), 77 (23%) had used POS during a 4-month period. Patients who reported an oncologist-recommended POS (odds ratio [OR] = 6.27, 95% confidence interval [CI] = 3.14-12.85) and those who were not sure if they had received a recommendation (OR = 4.64, 95% CI = 1.83-11.97) were more likely to attend POS than those who reported receiving no recommendation. Talking about psychosocial distress (OR = 0.74, 95% CI = 0.38-1.46) and providing detailed information about POS did not predict POS uptake (OR = 1.06, 95% CI = 0.46-2.38). CONCLUSIONS: Oncologists' expert recommendations to attend POS were strongly associated with patients' uptake of POS. The central role played by oncologists should be accounted for in stepped psycho-oncological care when POS referral pathways are defined.

Web-based counseling for families with parental cancer: Baseline findings and lessons learned.

Purpose: This is the first study in Switzerland to report on psychological adjustment in children of a parent with cancer using a web-based intervention during cancer therapy. Design/Sample: Twenty-two families participated in this randomized controlled web-based intervention program. Methods: Quality of life and emotional-behavioral well-being of children were examined using child self-reports, and parent proxy-reports. Furthermore, family communication and satisfaction and feedback on the web-based program were assessed. Findings: Children's first stage adjustment to parental cancer did not show detrimental patterns. The "lesson learned" in this setting emphasizes the challenge to reach families in need. The web-based program was appreciated as an additional source of information and support in this mostly highly functioning population. Conclusion: While feasibility was shown, it remains unclear how to contact families with lower psychosocial functioning.

Psychoneuroendocrine evaluation of an acceptance and commitment based stress management training.

BACKGROUND AND OBJECTIVES: Acceptance and Commitment Therapy (ACT), a behavioral therapy that targets psychological flexibility (PF), has been shown to be efficacious across a wide range of problems, including chronic work-related stress and perceived stress. ACT's effect on the multiple levels of the acute stress response (i.e., subjective and biological) is less well understood. The aim of the current study was to test whether ACT, by working toward PF, would reduce both the endocrine and subjective evaluations of participants' acute stress response. METHODS: Participants (n = 35) were randomized to an ACT condition or waitlist (WL). Participants in the ACT condition received a two-day ACT workshop on how to flexibly deal with stress. All participants completed a standardized laboratory stress test. RESULTS: The ACT and WL groups did not differ on main comparisons of the endocrine response (i.e., cortisol) or subjective evaluation. Baseline levels of PF moderated some outcomes. Avoidant participants had a stronger endocrine stress reaction if they received the ACT intervention. LIMITATIONS: The control condition was a WL and not an active intervention comparison. CONCLUSIONS: ACT is not useful in reducing the acute stress response and may even be iatrogenic, at least during tasks with little real-world impact for their personal values. Clinical or methodological significance of this article: This was one of the first studies to investigate the impact of an ACT intervention on biological parameters. The short-term intervention did not attenuate acute endocrine stress levels or subjective stress appraisals. Future studies should investigate which interventions and under which conditions attenuate acute and long-term stress responses.

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.

Agreement Between Parent- and Self-Reports of Psychopathic Traits and Externalizing Behaviors in a Clinical Sample.

A number of studies have identified discrepancies in informant ratings of externalizing behaviors in youth, but it is unclear whether similar discrepancies exist between informants when rating psychopathic traits. In this study, we examined parent-child agreement on ratings of both psychopathic traits and externalizing behaviors, and examined the factors that influence agreement in both of these domains. A total of 282 children between 7 and 16 years (M = 10.60 years, SD = 1.91) from an outpatient child psychiatric clinic participated in this study. Our findings revealed low levels of parent-child agreement on these measures (ICC values ranging from .02 to .30 for psychopathic traits; ICC values ranging from .09 to .30 for externalizing behaviors). In addition, our findings did not support the moderating effects of child's age, gender, clinical diagnosis, informant, and parental conflict on the relationship between parent- and child-ratings of psychopathic traits and externalizing behaviors. Further research is needed to better understand how parents and child reports of child's externalizing behaviors and psychopathic traits are similar and/or different from one another and factors that influence these agreements.

Web-based stress management for newly diagnosed cancer patients (STREAM-1): a randomized, wait-list controlled intervention study.

BACKGROUND: Being diagnosed with cancer causes major psychological distress, yet the majority of newly diagnosed cancer patients lack psychological support. Internet interventions overcome many barriers for seeking face-to-face support and allow for independence in time and place. We assess efficacy and feasibility of the first web-based stress management intervention (STREAM: STREss-Aktiv-Mindern) for newly diagnosed, German-speaking cancer patients. METHODS/DESIGN: In a prospective, wait-list controlled trial 120 newly diagnosed cancer patients will be included within 12 weeks of starting anti-cancer treatment and randomized between an immediate (intervention group) or delayed (control group) 8-week, web-based intervention. The intervention consists of eight modules with weekly written feedback by a psychologist ("minimal-contact") based on well-established stress management manuals including downloadable audio-files and exercises. The aim of this study is to evaluate efficacy in terms of improvement in quality of life (FACT-F), as well as decrease in anxiety and depression (HADS), as compared to patients in the wait-list control group. A sample size of 120 patients allows demonstrating a clinically relevant difference of nine points in the FACT score after the intervention (T2) with a two-sided alpha of 0.05 and 80 % power. As this is the first online stress management intervention for German-speaking cancer patients, more descriptive outcomes are equally important to further refine the group of patients with the largest potential for benefit who then will be targeted more specifically in future trials. These descriptive endpoints include: patients' characteristics (type of cancer, type of treatment, socio-demographic factors), dropout rate and dropout reasons, adherence and satisfaction with the program. DISCUSSION: New technologies open new opportunities: minimal-contact psychological interventions are becoming standard of care in several psychological disorders, where their efficacy is often comparable to face-to-face interventions. With our study we open this field to the population of newly diagnosed cancer patients. We will not only assess clinical efficacy but also further refine the target population who has the most potential to benefit. An internet-based minimal-contact stress management program might be an attractive, time- and cost-effective way to effectively deliver psychological support to newly diagnosed cancer patients and an opportunity to include those who currently are not reached by conventional support. TRIAL REGISTRATION: ClinicalTrials.gov NCT02289014 .

Psychosocial Stress-Induced Analgesia: An Examination of Effects on Heat Pain Threshold and Tolerance and of Neuroendocrine Mediation.

Stress-induced analgesia (SIA) is an adaptive response of reduced nociception following demanding acute internal and external stressors. Although a psychobiological understanding of this phenomenon is of importance for stress-related psychiatric and pain conditions, comparably little is known about the psychobiological mechanisms of SIA in humans. The aim of this study was to investigate the effects of acute psychosocial stress on heat pain perception and its possible neuroendocrine mediation by salivary cortisol levels and α-amylase activity in healthy men. Employing an intra-individual assessment of heat pain parameters, acute psychosocial stress did not influence heat pain threshold but significantly, albeit slightly, increased heat pain tolerance. Using linear mixed-model analysis, this effect of psychosocial stress on heat pain tolerance was not mediated by increases of salivary cortisol and state anxiety levels or by the activity of α-amylase. These results show that while psychosocial stress is selectively analgesic for heat pain tolerance, this observed effect is not mediated by stress-induced increases of salivary cortisol and α-amylase activity, as proxies of both the hypothalamus-pituitary-adrenal axis and the autonomic nervous system activation.

Disclosure of incidental constituents of psychotherapy as a moral obligation for psychiatrists and psychotherapists.

Informed consent to medical intervention reflects the moral principle of respect for autonomy and the patient's right to self-determination. In psychotherapy, this includes a requirement to inform the patient about those components of treatment purported to cause the therapeutic effect. This information must encompass positive expectancies of change and placebo-related or incidental constituent therapy effects, which are as important as specific intervention techniques for the efficacy of psychotherapy. There is a risk that informing the patient about possible incidental constituents of therapy may reduce or even completely impede these effects, with negative consequences for overall outcome. However, withholding information about incidental constituents of psychotherapy would effectively represent a paternalistic action at the expense of patient autonomy; whether such paternalism might in certain circumstances be justified forms part of the present discussion.

Does It Matter Who Provides Psychological Interventions for Medically Unexplained Symptoms? A Meta-Analysis.

BACKGROUND: Patients with medically unexplained symptoms (MUS) are difficult to treat and cause high health-care costs. Psychological interventions might be a beneficial option for treating patients with MUS, but evidence is inconsistent. This meta-analysis compares the effectiveness of psychological interventions for MUS - delivered either by psychotherapists (PTs) or by general practitioners (GPs) - with that of usual care. METHOD: We conducted a systematic review and meta-analysis on randomised controlled trials of psychological interventions for MUS. Physical symptoms were the primary outcome, and physical functioning and psychological symptoms were the secondary outcomes. We pooled between-group effect sizes (ESs) after the treatment and at the follow-up in random-effects meta-regressions and stratified meta-analyses. We repeated these analyses with the intervention provider, intervention dose, MUS severity and methodological quality as predictors of relative intervention effects. RESULTS: A total of 3,225 patients in 20 studies were analysed. After the treatment, small and significant ESs were found for all 3 outcome domains (ES range: 0.13-0.19, all p < 0.05). Psychological interventions were more beneficial for physical symptoms when delivered by PTs than by GPs (p = 0.02). There was no difference between PTs and GPs in terms of physical functioning and psychological symptoms. CONCLUSION: Psychological interventions are effective for patients with MUS, but the effects are small and most likely of short duration. Interventions that are delivered by PTs appear to have larger effects on unexplained physical symptoms than those delivered by GPs. Whether this superiority is due to a larger number of sessions of PT interventions remains unclear from our findings.

Internet-based stress management for women with preterm labour--a case-based experience report.

Pregnant women with preterm labour (PTL) in pregnancy often experience increased distress and anxieties regarding both the pregnancy and the child's health. The pathogenesis of PTL is, among other causes, related to the stress-associated activation of the maternal-foetal stress system. In spite of these psychobiological associations, only a few research studies have investigated the potential of psychological stress-reducing interventions. The following paper will present an online anxiety and stress management self-help program for pregnant women with PTL. Structure and content of the program will be illustrated by a case-based experience report. L.B., 32 years (G3, P1), was recruited at gestational week 27 while hospitalized for PTL for 3 weeks. She worked independently through the program for 6 weeks and had regular written contact with a therapist. Processing the program had a positive impact on L.B.'s anxiety and stress levels, as well as on her experienced depressive symptoms and bonding to the foetus. As PTL and the risk of PTB are associated with distress, psychological stress-reducing interventions might be beneficial. This study examines the applicability of an online intervention for pregnant women with PTL. The case report illustrates how adequate low-threshold psychological support could be provided to these women.

Boosting open-label placebo effects in acute induced pain in healthy adults (BOLPAP-study): study protocol of a randomized controlled trial.

Introduction: Pain is a highly prevalent symptom in the hospital setting, but treatment options remain limited. Harnessing the placebo effect in an ethical manner could provide a new possibility to reduce pain in clinical practice. So called open-label placebos (OLP) have been shown to elicit significant effects in reducing acute pain. But, before implementation, more knowledge concerning the properties of OLPs is needed. This study aims to assess the duration of analgesic effects from OLP and to determine the possibility of boosting such effects. Methods and analysis: This is the protocol of an ongoing (first patient enrolled in March 2023) single-site randomized trial investigating OLPs in two parts (i.e., substudies). In both parts, pain will be induced in healthy adults using an intradermal electrical stimulation model. Participants in Part 1 will have two study visits: An interventional visit with one OLP injection accompanied by an evidence-based treatment rationale and a control visit with no treatment. For Part 2, participants will be randomized into three groups: (1) A fixed-time "Booster" group including one single repetition of the OLP injection at a fixed time point, (2) an on-demand "Booster" group including one single repetition of the OLP injection on-demand, and (3) a control group who will receive just one OLP injection. Differences in pain ratings over time (using the Numeric Rating Scale) will be analyzed with several two-sample t-tests. The time point for a fixed-time "Booster" in Part 2 will be derived from Part 1 with additional statistical tools such as a broken-stick mixed-effect model. Discussion: This study aims to further characterize the analgesic effects of OLPs. In doing so, it will provide valuable information needed for later implementation of OLPs in clinical practice, where they could play a role in multimodal analgesic concepts. Ethics and dissemination: The "Ethikkommission Nordwest- und Zentralschweiz" (BASEC 2023-00296) approved the study protocol. Results of the analysis will be submitted for publication in a peer-reviewed journal. Clinical Trial Registration: This study is registered at ClinicalTrials.gov (NCT05819476) and is listed in the Swiss National Registry at kofam.ch (SNCTP000005470).