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NUMINOUS adj. /ˈnuːmɪnəs/ A term derived from the Latin numen, meaning "arousing spiritual emotion; mysterious or awe-inspiring."

Unveiling the use of Ketamine for Treating Depression

Article Title: “Experiences of Awe Mediate Ketamine’s Antidepressant Effects: Findings From a Randomized Controlled Trial in Treatment-Resistant Depression”

Authors: Julia Aepfelbacher, Benjamin Panny, and Rebecca B. Price

Publication Date: July 2024

DOI: 10.1016/j.bpsgos.2024.100316


Depression is a significant global health issue, predicted to become the leading cause of disease burden in the coming decade. Traditional antidepressants often fail to provide relief for treatment-resistant depression, necessitating the exploration of novel treatments like ketamine. Ketamine, an NMDA receptor antagonist, has shown rapid antidepressant effects, yet its exact psychological mechanisms remain unclear.


Study Overview

This study investigated whether the experience of awe during ketamine infusion contributes to its antidepressant effects. Conducted as a randomised controlled trial, the research included 116 participants with treatment-resistant depression. Participants were divided into two groups: one received ketamine infusions, while the other received a saline placebo. Researchers measured experiences of awe using the Awe Experience Scale (AWE-S) and compared them with dissociative effects using the Clinician-Administered Dissociative States Scale (CADSS).

Key Findings

The study found that ketamine infusions induced strong feelings of awe in participants, unlike saline infusions. These awe experiences significantly correlated with improvements in depression scores at multiple time points (24 hours, 5, 12, 21, and 30 days post-infusion). The mediation analysis revealed that awe experiences mediated the relationship between ketamine and depression outcomes, while general dissociative effects did not.


The psychological experience of awe appears to play a crucial role in ketamine’s antidepressant effects. Unlike general dissociative symptoms, awe seems to enhance the therapeutic impact of ketamine, suggesting that the emotional and cognitive components of the drug’s effects are vital. This finding shifts the focus from ketamine’s molecular mechanisms to its potential to evoke profound psychological experiences that contribute to its efficacy.


These insights could revolutionise how ketamine is administered in clinical settings. By fostering an environment that enhances the awe-inspiring effects of ketamine, healthcare providers might improve its therapeutic outcomes. Additionally, integrating practices that promote mindfulness and awe could extend the duration and impact of ketamine’s antidepressant effects.

Potential Application

The study’s findings highlight the potential for combining ketamine treatments with psychological interventions designed to evoke awe. This approach could enhance the effectiveness of ketamine therapy, providing a more holistic treatment for depression. Further research is needed to explore how these psychological elements can be maximised in clinical practice.


The research highlights the importance of awe in mediating ketamine’s antidepressant effects, offering a new perspective on its therapeutic potential. By understanding and leveraging these psychological mechanisms, we can develop more effective treatments for depression, particularly for those resistant to traditional therapies.



Aepfelbacher, J., Panny, B., & Price, R. B. (2024). Experiences of awe mediate ketamine’s antidepressant effects: Findings from a randomized controlled trial in treatment-resistant depression. Biological Psychiatry: Global Open Science, 4, 100316.

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