Effects of Open-Label Placebos on State Anxiety and Glucocorticoid Stress Responses

Abstract

Stress belongs to the most frequent negative feelings people are confronted with in daily life. Strategies against acute stress include, e.g., relaxation techniques or medications, but it is also known that placebos can successfully reduce negative emotional stress. While it is widely held that placebos require deception to provoke a response, recent studies demonstrate intriguing evidence that placebos may work even without concealment (e.g., against anxiety or pain). Most of these studies are based on self-report questionnaires and do not include physiological measures. Here we report results of a study examining whether placebos without deception reduce acute stress. A total of 53 healthy individuals received either placebos without deception or no pills before participating in a laboratory stress test (Maastricht Acute Stress Test, MAST). We recorded self-report stress measures and cortisol responses before and after the MAST. Results showed no significant differences between the placebo and the control group, but when comparing participants with high relative to low beliefs in the power of placebos we found significant lower anxiety and cortisol responses for the placebo believers. These results show that non-deceptive placebos may successfully reduce acute anxiety and stress, but only in participants who had a strong belief in placebos. We discuss the results by suggesting that open-label placebos might be a possible treatment to reduce stress at least for some individuals.

Neural underpinnings of open-label placebo effects in emotional distress

“…We report that an OLP treatment reduced self-reported measures of emotional distress in healthy subjects, which is in line with previous literature on effects of OLPs on emotional distress or anxiety (e.g., [7,12,13]). Moreover, we also replicated this beneficial effect of OLPs on emotional distress in an fMRI environment, allowing us to understand the neural mechanisms underlying the OLP effect.…”

“…For example, Mathur et al examined whether OLPs affect wound healing and found no results [10]. Leibowitz et al investigated physiological allergic responses and found no direct main effects, but an interaction with the belief in placebos ( [11] similar [12]). Guevarra et al employed an electroencephalographic (EEG) approach to examine emotional distress in healthy subjects and reported OLP effects on EEG markers for both, neutral and negative stimuli [13].…”

Deceptive and open-label placebo effects in experimentally induced guilt: a randomized controlled trial in healthy subjects

“…Empirically, our findings show that deceptive and open placebos were equally efficacious in reducing the selfconscious emotion of guilt. These findings are in line with a growing number of reports that have found OLPs to have significant effects on emotions, including anxiety 36,71 , depression 37,38 , sadness 16,28 , general emotional wellbeing 72,73 , and emotional distress 74 . Furthermore, our results are also in line with studies reporting that DPs and OLPs have equal effects in healthy subjects 21,22,57 , which highlights the potential of OLPs as a means of ethically harnessing placebo effects in these conditions.…”

Open-label placebos—a systematic review and meta-analysis of experimental studies with non-clinical samples

“…Five studies investigated the effect of an OLP on pain 16 , 22 , 25 , 28 , 29 . Three studies examined the influence of OLPs on well-being 19 , 23 , three on stress 18 , 31 , and two on arousal 32 , 34 . OLPs have also been studied in relation to wound healing 26 , sadness 24 , itchiness 27 , test anxiety 30 , cycling performance 21 , physiological recovery 33 , and muscle strength and fatigue 20 .…”

“…OLPs have also been studied in relation to wound healing 26 , sadness 24 , itchiness 27 , test anxiety 30 , cycling performance 21 , physiological recovery 33 , and muscle strength and fatigue 20 . A wide range of placebos was used in the studies, including a nasal spray 18 , 24 , 29 , pills 23 , 26 , 30 , 31 , creams 16 , 25 , 28 , capsules 20 , 21 , bottled water 19 , decaffeinated coffee 32 , 34 , verbal suggestions 27 , acupuncture 33 , and intravenous injection 22 . The degree of instructional suggestiveness was similarly distributed across studies, with five studies receiving a rating of 0 regarding the degree of instructional suggestiveness 24 , 29 , 32 – 34 , six studies receiving a rating of 1 18 – 20 , 27 , four studies receiving a rating of 2 21 , 25 , 26 , 28 , and five studies receiving a rating of 3 16 , 22 , 23 , 30 , 31 .…”