Study investigates the interplay between acute stress and placebo effects in nausea

By Pooja Toshniwal PahariaReviewed by Danielle Ellis, B.Sc.Jun 21 2023

In a recent study published in Scientific Reports, researchers investigated the interplay between acute stress and placebo effects on nausea.

Background

Placebo effects are observed following placebo treatments but can also alter the overall impact of any intervention. Placebo research aims to improve our understanding of contextual factors' effects on placebo effects such as stress, which, despite being common in clinical scenarios and integrating biological, social, and psychological components, has not been extensively investigated.

Biological components encompass the physiological changes in response to stress, including the secretion of stress hormones such as adrenaline and cortisol; psychological components comprise emotions such as anxiety and fear and cognitive assessments of the situation at hand; and social components include the environmental and social influences on stress responses, including interactions with friends and family, which can reduce the effects of stress.

Likewise, placebo effects depend on social, psychological, and biological interactions. Nausea is often experienced during stress, such as surgery or chemotherapy. Studies have reported clinically meaningful effects of placebo treatment on nausea; however, the impact of stress on these effects is not well characterized, warranting further research.

About the study

In the present randomized controlled trial, researchers investigated the impact of acute stress-induced negative-type emotions on the effects of placebo intervention in nausea.

The team aimed to induce significant stress, including cortisol release, to simulate the stress intensity among patients in clinical settings. The study included 80 healthy females aged 18 to 40 with motion sickness susceptibility, as determined using the Motion Sickness Susceptibility Questionnaire (MSSQ). The participants were randomized to undergo the Maastricht Acute Stress Test (MAST) or face a non-stressful condition and receive either placebo therapy (n=41; 20 stress and 21 no stress) or no therapy (n=39; 19 stress and 20 no stress).

The treatment group participants received a positive verbal suggestion of nausea improvement, followed by transcutaneous electrical nerve stimulation (TENS) therapy for 20 minutes. In the placebo intervention, the TENS electrodes were attached distoproximal to dummy acupuncture points on the ulnar forearm region, followed by superficial TENS massage for 20.0 minutes. The team induced nausea with a virtual optokinetic drum and repeatedly assessed humoral, behavioral, and psychophysiological parameters. Time estimation was included as a study outcome.

The Numerical Rating Scale (NRS) was used for changes in nausea, mood, and inner tension ratings, and the Visual Analogue Scale (VAS) was used to evaluate time perception changes. The State-Trait Anxiety Inventory (STAI) was used to record participant anxiety. Electrogastrogram (EGG) data were analyzed for physiological evaluation. The team estimated Pearson's correlations, applied Bonferroni corrections, and performed post hoc analyses.

An explorative analysis was performed by changing parameters from the baseline to deepen understanding of the associations between the gastric normal-to-tachy (NTT) ratios and motion sickness, nausea, negative emotions, time estimation, and stress. The team excluded individuals contraindicated for TENS use, those with somatic, psychiatric, or depressive conditions, inner ear infections, regular use of medications (other than L-thyroxine, allergic rhinitis medications, and hormonal contraceptives), and pregnant/lactating females.

Results

The mean participant age was 24 years; they were formally educated for 18 years; all individuals spoke German fluently; most were Caucasians; and 63.0% of them consumed hormonal contraceptive medications. Manipulation checks confirmed negative emotions and elevated salivary cortisol values among stressed individuals. Among non-stressed individuals, placebo therapy improved nausea and motion sickness symptoms and increased myoelectrical activities in the gastric tissues (NTT).

Among stressed individuals, the placebo therapy benefits on motion sickness and nausea persisted, whereas the NTT ratios did not improve. After the placebo treatment, nausea severity was significantly lowered, confirming that positive expectations were induced following placebo therapy. Stress neither affected nausea expectations nor interacted with treatment. The placebo intervention significantly decreased the Subjective Symptoms of Motion Sickness (SMSS) scores, whereas stress showed no interaction with the placebo effect on the SSMS values.

The NTT ratios showed significant stress-treatment interactions; placebo effects were observed among non-stressed participants but not among stressed ones. Further, the stressful conditions increased the NTT ratios among untreated but not among individuals treated with the placebo. Post-hoc analyses indicated perceptions of a swifter time passage following placebo treatment among non-stressed individuals but not among stressed individuals. Stress quickened subjective time passage among untreated individuals but not among placebo-treated ones.

Among stressed individuals, cortisol values were significantly higher than baseline post-MAST and prior to the optokinetic stimulus onset. Among non-stressed individuals, cortisol levels were significantly lower than baseline after rest and nausea. Lower ratings for mood were observed among stressed individuals compared to non-stressed ones post-MAST and prior to the optokinetic stimulus onset. Among stressed individuals, mood ratings reduced from baseline for all measurements, whereas among non-stressed ones, mood decreased significantly from baseline for rest and nausea.

In stressed individuals, anxiety increased from baseline to MAST and rest, whereas among non-stressed ones, it increased from baseline to rest only. Inner tension ratings were significantly higher after the MAST among stressed individuals, with considerably lower tension ratings after nausea induction among placebo-treated individuals than untreated ones. The exploratory analysis showed negative correlations between the NNT ratios and nausea in non-stressed participants and positive correlations between the ratios and inner tension ratings among stressed ones.

Based on the study findings, placebo effects on nausea and motion sickness symptoms were recalcitrant to experimentally-induced stress.