Ketamine’s rapid relief of suicidal thoughts may be linked to an increase in morning cortisol

A recent clinical trial discovered that a single dose of ketamine often raises morning cortisol levels in individuals struggling with major depression and suicidal thoughts. The research, published in the Journal of Affective Disorders, sheds light on the potential hormonal mechanism behind the rapid relief of suicidal ideation provided by ketamine.

Cortisol, a stress hormone produced by the adrenal glands, normally peaks in the early morning to help the body wake up. The cortisol awakening response, a spike in cortisol shortly after waking, is linked to stress response, mood, and cognitive function. Severe depression often disrupts this stress response system, resulting in abnormal morning cortisol levels.

The trial aimed to investigate if ketamine's rapid antidepressant effects are connected to alterations in cortisol levels, particularly the morning cortisol spike. Out of 80 participants between 18 and 65 years old experiencing major depressive disorder and scoring high on suicidal ideation assessments, 63 completed the study. Researchers administered either a sub-anesthetic dose of ketamine (0.5 milligrams per kilogram of body weight) or the sedative midazolam (0.02 milligrams per kilogram) to the participants.

Saliva samples were collected before the infusion and 24 hours later to measure cortisol changes. Participants in the ketamine group showed an increase in waking cortisol levels from 0.42 to 0.80 24 hours post-treatment, while the midazolam control group's scores decreased slightly from 0.97 to 0.77. These results suggest that ketamine's rapid antidepressant effects may be linked to its impact on cortisol levels, specifically the cortisol awakening response.