Ketamine infusion strongly induced feelings of awe in people with depression, and these awe experiences consistently predicted and mediated improvements in depression scores over 1 to 30 days, unlike general dissociative effects, which did not mediate outcomes. In a study of 116 participants with depression, 77 received a ketamine infusion and 39 received saline placebo. Awe was measured 40 minutes after infusion, and depression severity was assessed at five time points afterward. Awe scores were significantly higher in the ketamine group and statistically mediated the relationship between ketamine and depression improvement at all time points, suggesting that the awe-inspiring properties of ketamine may contribute to its antidepressant effects.
Adding mindfulness, music, and a light-occluding eye mask during ketamine infusion for depression did not improve antidepressant effects compared to ketamine alone, but it enriched the subjective experience. Participants in the combined sensory intervention group reported deeper engagement, a stronger sense of connection to reality, increased focus, moments of relief from sadness, and feelings of awe and spiritual insight. However, four individuals in that group reported discomfort. The findings suggest that while the sensory interventions make the experience more meaningful for many, they may cause discomfort for a few, and making them optional could avoid this.