Placebo Control Condition Research Articles

Medication development for AUD: A systematic review of clinical trial methodology

Refining clinical trial methodology has become increasingly important as study design is shown to influence treatment efficacy. To maximize the efficiency of randomized clinical trials (RCTs), researchers aim to establish standardized practices. The goal of this systematic review is to describe methodological practices of clinical trials for alcohol use disorder (AUD) over the past 40 years. To achieve this goal, a PubMed search was conducted in April 2023 for RCTs on AUD medications published between July 2018 through April 2023. Resulting studies were combined with a previous search from 1985 through 2018. Inclusion criteria for the RCT studies were: (1) a randomized controlled trial, (2) double or single blinded, (3) placebo or active control condition, (4) alcohol use as the primary endpoint, (5) 4 or more weeks of treatment, and (6) 12 or more weeks of follow-up. In total, methodological data from 139 RCTs representing 19 medications and spanning the past four decades were summarized. Results indicated that the most common medications tested were naltrexone (k = 42), acamprosate (k = 24), and baclofen (k = 11). On average, participants were 74% male and consumed 226 drinks per month pre-randomization. The median length of treatment was 12 weeks (IQR = 12–16; min = 4 max = 52) and the median follow-up duration was 12.5 weeks (IQR: 12–26; min = 7 max = 104). There were two broad domains of outcomes (i.e., abstinence and heavy drinking), with most studies featuring outcomes from both domains (k = 87; 63%). Reporting practices were summarized by decade, revealing an increased enrollment of females, better reporting of race and ethnicity data, and less studies requiring pre-trial abstinence. This review summarizes the current state of the literature on randomized clinical trials for AUD including effect sizes for individual studies and summaries of key methodological features across this representative set of clinical trials.

Intentional Imperfection Program: A pilot randomised controlled trial to help university students manage perfectionism

Given that perfectionism has been associated with interpersonal, academic, and mental health difficulties in university students, helping them manage their perfectionism is crucial. This pilot trial examined the feasibility, acceptability, and potential efficacy of an online perfectionism program designed to target the mechanisms that link perfectionism to psychological distress. Seventy first-year psychology students from Macquarie University with high levels of perfectionism were recruited into this two-arm pilot trial and randomised to either the intervention (i.e., perfectionism program) or attention placebo control (i.e., lifestyle program) condition. We assessed indicators of feasibility and acceptability, as well as measures related to perfectionism, psychological distress, emotion regulation skills, interpersonal and academic functioning at baseline, one-month post treatment, and three-month follow-up (blinded outcome assessment). Our analyses revealed that, while participants expressed overall satisfaction with the program, there was low engagement with it (Mcompletion rate=36.23%), and retention in the study was low (response rates for post-treatment: 65.71% and follow-up: 48.57%). Bearing this in mind, our linear mixed model analyses revealed greater reductions in perfectionistic traits and cognitions, interpersonal hostility, and loneliness, as well as increases in self-compassion in the intervention group compared to the control group at post-treatment and/or follow-up. However, we did not observe statistically significant changes in other important treatment outcomes (e.g.,psychological distress). Given these findings, adjustments to improve engagement and retention should occur before proceeding with a larger, definitive trial. This trial was retrospectively registered on the Australian and New Zealand Clinical Trials Registry (no. ACTRN12622000960752).

Virtual reality experiences for breathing and relaxation training: The effects of real vs. placebo biofeedback

Virtual reality biofeedback systems for relaxation training can be an effective tool for reducing stress and anxiety levels, but most of them offer a limited user experience associated to the execution of a single task and a biofeedback mechanism that reflects a single physiological measurement. Furthermore, user evaluations of such systems do not typically include a placebo condition, making it difficult to determine the actual contribution of biofeedback. This paper proposes a VR system for breathing and relaxation training that: (i) uses biofeedback mechanisms based on multiple physiological measurements, (ii) provides a richer user experience through a narrative that unfolds in phases where the user is the main character and controls different elements of the virtual environment through biofeedback. To evaluate the system and to assess the actual contribution of biofeedback, we compared two conditions involving 35 participants: a biofeedback condition that exploited real-time measurements of user's breathing, skin conductance, and heart rate; and a placebo control condition, in which changes in the virtual environment followed physiological values recorded from a session with another user. The results showed that the proposed virtual experience helped users relax in both conditions, but real biofeedback produced results that were superior to placebo biofeedback, in terms of both relaxation and sense of presence. These outcomes highlight the important role that biofeedback can play in virtual reality systems for relaxation training, as well as the need for researchers to consider placebo conditions in evaluating this kind of systems.

Do Character Strengths-Based Interventions Change Character Strengths? Two Randomized Controlled Intervention Studies

Character strengths-based interventions are effective for increasing well-being. However, whether such interventions also change character strengths has never been tested. In Study 1, we studied the effects of seven different variants of character strengths-based interventions on well-being, ill-being, and character strengths traits and states (i.e., frequency of behavior during one week). We analyzed data of N = 1,163 participants (82.3% women, aged 18 to 78; Md = 45) who were randomized to seven intervention conditions lasting one week; (1) learning about the VIA classification of character strengths, (2) learning about one’s own strengths, using signature strengths (3) in a new way, (4) with a minor challenge, (5) with a larger challenge, (6) for other people, (7) forming a strengths-based habit, or a placebo control condition (early memories). Results showed that using signature strengths in a new way led to increased well-being, social well-being, as well as character strengths states and traits. Forming a strengths-based habit also increased well-being and character strengths states. No effects on ill-being were found. In Study 2, we tested a four-week multi-component program that combined several interventions tested in Study 1 in a sample of N = 254 participants (77.8% women, aged 19 to 87; Md = 42). Compared to a waitlist control group, the intervention condition showed increases in well-being and character strengths states, and reductions in stress and neuroticism. We conclude that character strengths interventions may not only affect well-being but also character strengths states and traits, as well as broader personality traits such as neuroticism.

Psychosocial and pharmacologic interventions to reduce harmful alcohol use in low- and middle-income countries.

Psychosocial and pharmacologic interventions to reduce harmful alcohol use in low- and middle-income countries.

A Brief Internet-Based Passive Psychoeducation Intervention to Promote Healthy Relationships Among Young Adults: A Pilot Randomised Placebo-Controlled Trial.

This pilot randomized controlled trial tested the potential efficacy of a brief internet-based, passive psychoeducation intervention, Free From Abuse, in promoting healthy relationships among young adults. Participants aged 18 to 24 years were randomly assigned to an intervention treatment (n = 71) or a placebo control condition (n = 77). Participants in the treatment arm had a larger increase in recognition of abusive behavior and reduction in domestic violence myth acceptance scores than participants in the control arm postintervention and after one week. This study provides preliminary evidence that brief internet-based passive psychoeducation is potentially useful in promoting healthy relationships among young adults.

The complex clinical response to selective serotonin reuptake inhibitors in depression: a network perspective

The clinical response to selective serotonin reuptake inhibitors (SSRIs) in depression takes weeks to be fully developed and is still not entirely understood. This study aimed to determine the direct and indirect effects of SSRIs relative to a placebo control condition on clinical symptoms of depression. We included data of 8262 adult patients with major depression participating in 28 industry-sponsored US Food and Drug Administration (FDA) registered trials on the efficacy of SSRIs. Clinical symptoms of depression were assessed by the 17 separate items of the Hamilton Depression Rating Scale (HDRS) after 1, 2, 3, 4 and 6 weeks of treatment. Network estimation techniques showed that SSRIs had quick and strong direct effects on the two affective symptoms, i.e., depressed mood and psychic anxiety; direct effects on other symptoms were weak or absent. Substantial indirect effects were found for all four cognitive symptoms, which showed larger reductions in the SSRI condition but mainly in patients reporting larger reductions in depressed mood. Smaller indirect effects were found for two arousal/somatic symptoms via the direct effect on psychic anxiety. Both direct and indirect effects on sleep problems and most arousal/somatic symptoms were weak or absent. In conclusion, our study revealed that SSRIs primarily caused reductions in affective symptoms, which were related to reductions in mainly cognitive symptoms and some specific arousal/somatic symptoms. The results can contribute to disclosing the mechanisms of action of SSRIs, and has the potential to facilitate early detection of responders and non-responders in clinical practice.

Meta-analysis of sleep deprivation in the acute treatment of bipolar depression.

Sleep deprivation (SD) is an antidepressant intervention with multiple administration formats that has been investigated primarily with uncontrolled clinical trials and qualitative reviews of the literature. The validity and applicability of these findings to the treatment of bipolar depression (BPD) is uncertain. A PRISMA-based systematic review of the literature and meta-analysis were conducted to determine the efficacy of SD in the treatment of BPD and to identify moderator variables that influence response rate. From a sample of 15 studies covering 384 patients, the overall, mean response rate to SD was 47.6% (CI 36.0%, 59.5%). This response rate compared post-SD to pre-SD depression scores, and not to a placebo control condition. Of several potential moderating variables examined, the use of adjunctive pharmacotherapy achieved statistical significance with response rates of 59.4% [CI 48.5, 69.5] for patients using adjunctive medication vs 27.4% [CI 17.8, 39.8] for patients not using adjunctive medication. This meta-analysis of SD in the treatment of BPD found an overall, response rate of almost 50%, reinforcing earlier estimates of efficacy. The use of adjunctive pharmacotherapy had a statistically significant moderating effect on SD response suggesting that clinical practice should routinely pair these interventions. These findings provide a higher level of evidence supporting the use of SD, especially when used with medication, and should inform future management guidelines for the treatment of BPD.

Social Media Interventions for Risky Drinking Among Adolescents and Emerging Adults: Protocol for a Randomized Controlled Trial.

BackgroundDespite intervention efforts to date, the prevalence of risky drinking among adolescents and emerging adults remains high, increasing the risk for health consequences and the development of alcohol use disorders. Peer influences are particularly salient among this age group, including via social media. Thus, the development of efficacious early interventions for youth, delivered with a broad reach via trained peers on social media, could have an important role in addressing risky drinking and concomitant drug use.ObjectiveThis paper describes the protocol of a randomized controlled trial (RCT) testing the efficacy of a social media intervention among adolescents and emerging adults who meet the criteria for risky drinking (using the Alcohol Use Disorders Identification Test-Consumption [AUDIT-C]), delivered with and without financial incentives for participation, compared with an attention placebo control condition (ie, entertaining social media content), on alcohol consumption and consequences.MethodsThis RCT involved recruiting 955 youths (aged 16-24 years) via advertisements on Facebook and Instagram to self-administer a brief web-based screening survey. Those screening positive for past 3-month risky drinking (AUDIT-C positive: ages 16-17 years: ≥3 females and ≥4 males; and ages 18-24 years: ≥4 females and ≥5 males) were eligible for the RCT. After providing consent (a waiver of parental consent was obtained for minors), participants completed a web-based baseline survey and several verification procedures, including a selfie photo matched to Facebook profile photos. Participants were then randomized to join invitation-only secret Facebook groups, which were not searchable or viewable by parents, friends, or anyone not recruited by the study. The 3 conditions were social media intervention with incentives, social media intervention without incentives (SMI), and attention placebo control. Each condition lasted 8 weeks and consisted of bachelor’s-level and master’s-level therapist electronic coaches posting relevant content and responding to participants’ posts in a manner consistent with Motivational Interviewing. Participants in the control condition and SMI condition did not receive payments but were blind to condition assignment between these 2 conditions. Follow-ups are ongoing and occur at 3, 6, and 12 months poststart of the groups.ResultsWe enrolled 955 participants over 10 waves of recruitment who screened positive for risky drinking into the RCT.ConclusionsThe findings of this study will provide the critical next step in delivering early alcohol interventions to the youth, capitalizing on social media platforms, which could have significant public health impact by altering alcohol use trajectories of adolescents and emerging adults engaged in risky drinking.Trial RegistrationClinicalTrials.gov NCT02809586; https://clinicaltrials.gov/ct2/show/NCT02809586.International Registered Report Identifier (IRRID)DERR1-10.2196/16688

Carbohydrate mouth rinse has no effects on behavioral or neuroelectric indices of cognition

Rinsing the mouth with a carbohydrate solution has been suggested as a means to enhance aspects of both physical and cognitive performance. However, evidence in support of these assertions is relatively weak. The purpose of this study was to investigate the effects of a carbohydrate mouth rinse solution on motor speed, inhibition, and sustained attention as indexed by both behavioral and neuroelectric measures. Using a double-blind, placebo-controlled, within-subjects crossover design, 50 college-aged young adults performed a battery of cognitive tasks both before and after rinsing their mouth for 10 s with 20 mL of either a carbohydrate mouth rinse solution or a sensory-matched placebo control solution. A simple tapping task was used as a measure of motor speed, a modified Eriksen flanker task was used to index inhibition, and a rapid visual information processing task was used as a measure of sustained attention. Participants demonstrated longer reaction times in the Flanker task after rinsing their mouths with the carbohydrate mouth rinse, relative to pretest. No differences in reaction time were observed for the placebo control condition. P3 latency in the Flanker task as an index of attentional processing speed was shorter at posttest than at pretest in the placebo control – but not the carbohydrate mouth rinse – condition. These results suggest that despite claims of cognitive enhancement, carbohydrate mouth rinses do not appear to alter motor speed, inhibition, or sustained attention as compared to a placebo control in non-physically-fatigued college-aged adults.

An Experimental Comparison of Approaches to Training Insight

Abstract The purpose of the research was to investigate different types of training in insight problem solving. In doing so, we reviewed the literature on experimental tests of procedures for training insight problem solving. The results revealed that most procedures focused either on restructuring or divergent thinking, and provided some evidence for the effectiveness of both approaches. However, we found no studies that compared the effects of the two approaches. The article reports two experiments that compared different training procedures based on restructuring and divergent thinking. For the latter, the methods focused separately on fluency, flexibility and originality training. The first experiment compared a restructuring approach with fluency training and a placebo control condition. The results indicated that the restructuring training was significantly more effective than the others, but only when instructions were verbal, not in script form. The second experiment compared restructuring training with flexibility, fluency and originality training, all presented in script form, and the results indicated that the restructuring training was significantly more effective than both fluency training and flexibility training. Implications for future research are discussed.

Enhancing Student’s Self-Leadership Through a Positive Psychology Intervention? A Randomized Controlled Trial Using an Idiographic Perspective

Positive psychology interventions have been shown to increase individual well-being and happiness at a nomothetic level. We expand our understanding of their potential impact on individual’s self-leadership by adopting an idiographic approach. Moreover, we compare that effect with that of a goal-setting intervention. In a diary study using a randomized controlled design, 60 undergraduates were surveyed daily for 14 consecutive days before an exam and were assigned to one of three conditions: a “three good things” (TGT) intervention in which participants wrote down three positive things they had experienced during the day before going to bed; a “goal-setting” (GS) intervention in which they wrote down three learning goals for the next day; or a placebo control condition. Dynamic modeling of time series revealed that students in the TGT and the GS intervention significantly increased their self-leadership across time at a small to medium effect size. Students in the placebo control group showed no significant change. Contrary to expectations, the TGT intervention was not more strongly associated with self-related strategies, and the GS intervention was not more strongly associated with task-related strategies. This study demonstrates the value of a brief positive psychology intervention, which is comparably effective as a goal-setting intervention in fostering individual self-leadership in academic achievement settings.

Attentional bias modification with a new paradigm: The effect of the Detection Engagement and Savoring Positivity (DESP) task on eye-tracking of attention

Background and objectivesWe tested the effect of a new Attentional Bias Modification (ABM) task - the Detection Engagement and Savoring Positivity (DESP) task - on attentional biases. The DESP is innovative in that it involves a procedure of savoring the positivity of various pictures. MethodsParticipants were randomly assigned to the DESP or to a placebo control condition (experiment 1; n = 38) or a condition controlling for savoring (experiment 2; n = 54) in a pre-post/training experimental design. During one week, the participants completed the DESP or the control task once a day between three and six times. We assessed the effects of the DESP task on various attentional biases (i.e. positive, negative and threat) by computing dwell time from an eye-tracking technology before and after the training, and also one week after the post-training session in experiment 2. ResultsIn both experiments, the attentional bias toward positive stimuli between the pre- and the post-training increased significantly more in the DESP task condition than in the control conditions. Negative and threat attentional biases were not significantly affected by the experimental manipulations. Experiment 2 revealed that the DESP task – including the savoring instruction – increased significantly more the positive attentional bias than a task excluding this step and that this effect remained significant one week after the post-training session. LimitationsOur samples were mainly composed of women participants. This prevents generalization of the findings. ConclusionsThe DESP task offers promising perspectives for sustainably improving attention to positive information.

The impact of lifestyle Physical Activity Counselling in IN-PATients with major depressive disorders on physical activity, cardiorespiratory fitness, depression, and cardiovascular health risk markers: study protocol for a randomized controlled trial

BackgroundMajor depressive disorder (MDD) is a widespread and burdensome psychiatric issue. Physical activity counselling may increase lifestyle physical activity and cardiorespiratory fitness in this specific and particularly vulnerable population, which often suffers from both mental and physical health problems. Therefore, this study will examine the impact of a lifestyle physical activity counselling intervention on physical activity, cardiorespiratory fitness, depression, and cardiovascular health risk markers among in-patients diagnosed with MDD compared to controls. Secondary purposes are to examine the acceptability and perceived usefulness of the intervention among these patients, to find out whether the effectiveness of the intervention is moderated by genetic factors, and to compare baseline values with an age- and gender-matched group of healthy controls.MethodsThe study is designed as a multi-centric two-arm randomized clinical trial including an intervention group and a placebo control group, allocation concealment, single-blinding, and intention-to-treat analysis. Participants (N = 334) will be continuously recruited from four clinics specialized in the treatment of MDD. The intervention builds on a standardized, theory-based, low-cost lifestyle physical activity counselling programme, which was specifically designed for an in-patient rehabilitation setting. The placebo control condition consists of general instructions about health-enhancing physical activity. Data assessments will take place 2–3 weeks after admission to in-patient treatment (baseline), and 6 weeks (post) and 12 months (follow-up) after discharge from in-patient treatment. The primary outcome is objectively assessed physical activity at follow-up.DiscussionBecause regular physical activity has proven to be an important predictor of long-term response and remission in patients with major depression, we believe that our planned study may lay important groundwork by showing how individually tailored lifestyle physical activity counselling can be integrated into given clinical structures. Improving physical activity may have important implications for tackling metabolic and cardiovascular disease and increasing mood and cognitive functioning in this at-risk population, hence limiting the future burden of multiple chronic conditions. Increased physical activity may also reduce the likelihood of future depressive episodes. By moving towards the primary prevention of chronic physical conditions, much can be done to enhance the quality and quantity of life of people with MDD.Trial registrationISRCTN, ISRCTN10469580. Registered on 3 September 2018.

A randomized controlled trial of well-being therapy to promote adaptation and alleviate emotional distress among medical freshmen

BackgroundMaladjustment and emotional distress are extremely prevalent among first-year medical students in college and are associated with numerous negative consequences for medical freshmen, their families and universities. The current research aimed to detect the efficacy of a well-being therapy in promoting adaptation to college life and alleviating emotional distress among medical freshmen.MethodsOne hundred one participants who met the inclusion criteria were enrolled in a single-blind randomized controlled trial. Well-being therapy was given to the intervention group weekly for 5 weeks (WBT, n = 50). At the same time, students in the placebo control condition (CC, n = 51) were required to record early memory for 5 weeks and at weekly meetings it would be shared voluntarily. Psychological well-being, adaptation, anxiety and depression were recorded at pretest, posttest, and at three-month follow-up. Data from 87 first-year students with complete follow-ups (WBT, n = 39; CC, n = 48) were analyzed over three time periods.ResultsCompared with the control group, students undergoing the 5-week well-being therapy reported larger improvements in psychological well-being and adaptation, and greater alleviation in symptoms of anxiety and depression from pretest to posttest to follow-up.ConclusionsWell-being intervention may provide first-year medical students with skills to efficiently manage maladjustment and emotional distress. It seems that medical freshmen would benefit a lot when such an intervention programme could be incorporated into the general medical education.Trial registration numberChiCTR-ROC-17012636. Registered 11 September 2017 (Retrospectively registered) at Chinese Clinical Trial Registry.

Alleviating Social Pain: A Double-Blind, Randomized, Placebo-Controlled Trial of Forgiveness and Acetaminophen.

Research has suggested that physical pain (e.g., caused by injury) and social pain (e.g., caused by social rejection) are modulated by some of the same biological systems. Consequently, it is possible that acetaminophen, which is commonly used to alleviate physical pain through neurochemical pathways, may have social pain-relieving effects that interact with forgiveness, which reduces social pain through psychological pathways. To date, however, only a few studies have examined how experiences of social pain change over time, and none have examined how acetaminophen and forgiveness interact to influence these effects. We addressed these issues by investigating how acetaminophen administration and daily forgiveness are associated with experiences of social pain over 21 days. We hypothesized that acetaminophen-related reductions in social pain across the 21-day study period would be greatest on days following high levels of forgiveness. To test this hypothesis, we conducted a double-blind, randomized, placebo-controlled trial in which we randomly assigned 42 healthy young adults to an acetaminophen condition (1,000 mg of acetaminophen daily), placebo-control condition (400 mg of potassium daily), or empty-control (no pill) condition. We then assessed their levels of forgiveness and social pain for 20 consecutive days. As hypothesized, acetaminophen reduced participants' social pain levels over time but only for those exhibiting high levels of forgiveness (i.e., 18.5% reduction in social pain over 20 days). These data are the first to show that forgiveness and acetaminophen have interactive effects on experiences of social pain, which is one of the most common and impactful of all human experiences.

The effects of three positive psychology interventions using online diaries: A randomized-placebo controlled trial

Three positive psychology interventions (coping humor, three funny things, three good things) were compared with a placebo control condition (early memories) in a randomized placebo-controlled online trial. A total of 182 healthy participants participated in a one week web-based diary study and completed evaluation measures at pre, post, and one month follow-up. They were recruited via e-mail and have been primarily students. Primary outcomes have been happiness and depressive symptoms, secondary outcomes coping humor, cheerfulness (and its subscales), and subjective perceived change. The intention-to-treat analysis (ITT) using linear mixed models could not replicate the positive effects of past research. When compared to the control condition, only the coping humor intervention influenced primary outcomes (r = 0.24–0.29). Three funny things and three good things had no effects at all. Secondary outcomes showed only isolated effects, so that no uniform effect pattern was found for the interventions. Reasons for the small effects, such as motivation and psychosocial status of the participants, as well as recommendations for future studies are discussed.

Evaluative conditioning as a body image intervention for adolescents with eating disorders.

The aim was to investigate whether a computer-based evaluative conditioning intervention improves body image in adolescents with an eating disorder. Positive effects were found in earlier studies in healthy female students in a laboratory and a field setting. This study is the first to test evaluative conditioning in a clinical sample under less controlled circumstances. Fifty-one adolescent girls with an eating disorder and a healthy weight were randomly assigned to an experimental condition or a placebo-control condition. The computerized intervention consisted of six online training sessions of 5 min, in which participants had to click on pictures of their own and other people's bodies. Their own pictures were systematically followed by portraits of friendly smiling faces. In the control condition, participants were shown the same stimuli, but here, a stimulus was always followed by another stimulus from the same category, so that own body was not paired with smiling faces. Before, directly after, three weeks after, and 11 weeks after the intervention, self-report measures of body image and general self-esteem were administered. Automatic self-associations were also measured with an Implicit Association Test. In contrast to our hypotheses, we did not find an effect of the intervention on self-report questionnaires measuring body satisfaction, weight and shape concern, and general self-esteem. In addition, the intervention did not show positive effects on implicit associations regarding self-attractiveness. These findings do not support the use of evaluative conditioning in its present form as an intervention for adolescents in clinical practice. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Are Adverse Events Induced by the Acute Administration of Calcineurin Inhibitor Cyclosporine A Behaviorally Conditioned in Healthy Male Volunteers?

PurposeThe learned immunosuppressive placebo response has been demonstrated in experimental animals, healthy humans, and patients, and is suggested as a therapy for improving immunopharmacologic treatment. It remains unclear, however, whether potential adverse events induced by the drug are also behaviorally conditioned. Employing an established taste–immune learning paradigm in healthy humans using the calcineurin inhibitor and immunosuppressive drug cyclosporine A (CsA) as an unconditioned stimulus, we investigated whether and to what extent perceived adverse events induced by acute CsA administration are behaviorally conditioned. MethodsA total of 68 healthy male subjects were exposed to the established taste–immune learning paradigm, receiving either placebo or CsA (10 mg/kg) as an unconditioned stimulus, and a novel-tasting drink as a conditioned stimulus. FindingsSubjects repeatedly receiving CsA during acquisition reported significantly more adverse events than did placebo-receiving subjects. However, during reexposure to the conditioned stimulus, the reported adverse events did not differ from those in the placebo control condition. ImplicationsThese data indicate that acute adverse events are not behaviorally conditioned during the learned immunosuppressive response. Our results further strengthen the great potential clinical relevance of employing the learned immunosuppressive placebo response as a therapy to support immunopharmacologic regimens, ultimately aiming to reduce the medical dosages required, thereby minimizing adverse drug events while maximizing the therapeutic benefit in patients. German Clinical Trial Register (www.drks.de) identifier: DRKS00007693.

Relationship of a Special Acidified Milk Protein Drink with Cognitive Performance: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study in Healthy Young Adults.

A previous in vivo study with rats suggested that a special milk protein drink manufactured using an acidification procedure to suppress the aggregation of milk proteins was absorbed quickly after feeding. We performed a randomized, double-blind, placebo-controlled, repeated-measure crossover study to investigate the short-term effects on cognitive performance in 29 healthy young adult men after they consumed this drink in the morning. After an overnight fast, subjects were tested for performance in the Uchida–Kraepelin serial arithmetic test and the Stroop test as well as for subjective feeling, body temperature, and heart rate variability before and after consumption of either the acidified milk protein drink or an isoenergetic placebo drink. Subjects showed a significant improvement in performance in the Uchida–Kraepelin test, the primary outcome measured, when they consumed the acidified milk protein drink compared with the placebo control condition. In addition, consumption of the acidified milk protein drink, compared with the placebo control, was associated with increases in vagally-mediated heart rate variability indices which, from recent theoretical perspectives, may reflect a higher ability to modulate cognitive and behavioral processes. There was no significant difference in subjective feelings and body temperature between the test drink conditions. These data suggest that consumption of the acidified milk protein drink may improve cognitive performance, with possible involvement of physiological systems that regulate cognition and behavior.