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Introduction Despite growing evidence validating placebo effects in nausea, little is known about the underlying cortical mechanisms in women and men. Therefore, the present study examined sex differences and electroencephalography (EEG) characteristics of the placebo effect on nausea. Methods On 2 consecutive days, 90 healthy subjects (45 females) were exposed to a nauseating visual stimulus. Nausea was continuously rated on an 11‐point numeric rating scale, and 32 EEG channels were recorded. On day 2, subjects were randomly allocated to either placebo treatment or no treatment: the placebo group received sham acupuncture, whereas the control group did not receive any intervention. Results In contrast to the control group, both sexes in the placebo group showed reduced signs for anticipatory nausea in the EEG, indexed by increased frontal lobe and anterior cingulate activity. Among women, the improvement in perceived nausea in the placebo group was accompanied by decreased activation in the parietal, frontal, and temporal lobes. In contrast, the placebo‐related improvement of perceived nausea in men was accompanied by increased activation in the limbic and sublobar (insular) lobes. Conclusion Activation of the parietal lobe in women during the placebo intervention may reflect altered afferent activity from gastric mechanoreceptors during nausea‐induced tachyarrhythmia, whereas in men, altered interoceptive signals in the insular cortex might play a role. Thus, the results suggest different cerebral mechanisms underlying the placebo effects in men and women, which could have implications for the treatment of nausea.

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