This pilot study was aimed at evaluation of the translational potential of xenon as a potential antidepressant. In placebo-controlled double-blind study, 14 healthy right-handed volunteers were randomly assigned to 15-min inhalation session of either gas mixture with xenon (25%Хе/30%О2/45%N2) or placebo (70%N2/30%О2) with simultaneous recording of 64-channel EEG. To assess the dynamics and nature of emotional activation in response to xenon and placebo, we analyzed both the intensity of positive and negative emotions and individual alpha peak frequency (iAPF) of EEG. We found that xenon in sub-anesthetic doses promoted positive emotional arousal, and that emotional response to xenon depended on individual neurophysiological endophenotype of alpha-activity (iAPF). The authors suggest that iAPF shifts can be used as a neurophysiological predictor of individual thymoleptic response to xenon.