Ketamine's morning cortisol rise parallels rapid relief from suicidal thoughts in depression

A randomized controlled trial in adults with major depression and active suicidal ideation found that a single subanesthetic ketamine infusion increased waking morning cortisol 24 hours post-treatment (not seen with midazolam). This cortisol rise coincided with ketamine’s peak anti-suicidal effects, though the correlation with symptom improvement was modest and not consistently significant. The findings suggest cortisol changes may be involved in ketamine’s action on the stress-response system, but more research with more comprehensive sampling and sleep monitoring is needed to establish causality and clinical relevance.