Effects of ginger and expectations on symptoms of nausea in a balanced placebo design

Abstract

Objective: Ginger effects on (experimental) nausea have been described, but also strong placebo effects and sex differences when nausea is involved. The "balanced placebo design" has been proposed to allow better separation of drug and placebo effects.

Methods: Sixty-four healthy participants (32 women) were randomly assigned to receive an antiemetic ginger preparation or placebo, and half of each group was told to have received drug or placebo. They were exposed to 5×2 min body rotations to induce nausea. Subjective symptoms and behavioral (rotation tolerance, head movements) and physiological measures (electrogastrogram, cortisol) were recorded. Groups were balanced for sex of participants and experimenters.

Results: Ginger and the information given did not affect any outcome measure, and previous sex differences could not be confirmed. Adding the experimenters revealed a significant four-factorial interaction on behavioral but not on subjective or physiological measures Men who received placebo responded to placebo information when provided by the male experimenter, and to ginger information when provided by the female experimenter. This effect was not significant in women.

Conclusion: The effects of an antiemetic drug and provided information interact with psychosocial variables of participants and experimenters in reports of nausea.

Figure 1. Time schedule of the single session of the study in an individual participant.

Figure 2. Number of head movements in male and female participants (HM; means +/− SD).

Male (Panel A) and female (Panel B) participants received either ginger or placebo in a double-blinded design and (immediately prior to rotation) were informed to have received ginger or placebo in a balanced placebo-design, i.e. half of the participants of each group were correctly informed while the other half received false information. When the four groups were compared by effects of drug and information on symptom rating (SR), rotation tolerance (RT), and head movements (HM), MANOVA results were only significant when sex of participants and the experimenters were added as between factors to the analysis (F = 4.307, p = .009).

Figure 3. Electrogastrogram (EGG) in participants that received ginger or placebo.

EGG was evaluated as the ratio between normal activity (2.5 to 3.75 cycles per minute, cpm) and activity in the tachygastria band (4 to 9.75 cpm), and with increasing nausea the ratio usually falls below 1. Data segments were recorded at baseline, twice after drug application, and after rotation. The constant fall of the ratio from baseline to post rotation is interrupted in the ginger group but ginger was not able to prevent nausea to occur with rotation.

Figure 4. Electrogastrogram (EGG) in male and female participants that received ginger or placebo.

EGG was evaluated as the ratio between normal activity (2.5 to 3.75 cycles per minute, cpm) and activity in the tachygastria band (4 to 9.75 cpm), and with increasing nausea the ratio usually falls below 1. Data segments were recorded at baseline, twice after drug application, and after rotation. The constant fall of the ratio from baseline to post rotation was not different between men and women.