Ketamine, a dissociative anesthetic, produces rapid antidepressant effects at low doses, which may be partly due to its anti-inflammatory actions. This review examines ketamine's antidepressant properties and its influence on peripheral and central inflammation, aiming to clarify mechanisms that could make it a dual-action treatment for treatment-resistant depression (TRD) and suicidal ideation. Inflammation is linked to major depressive disorder (MDD) and poor treatment response, so medications that quickly address both inflammation and depressive symptoms could improve personalized care for psychiatric emergencies.
MDMA administration after severe stress reduces stress-enhanced fear learning in male rats, likely through an immunosuppressive mechanism. The drug lowered stress-induced increases in the pro-inflammatory cytokine IL-1β and reversed stress-induced reductions in the microglial marker IBA-1 in the dorsal hippocampus, while not affecting TNF-α or the astrocyte marker GFAP. These results support the hypothesis that MDMA blocks stress-enhanced fear learning via immune modulation and align with clinical findings on MDMA-assisted psychotherapy for PTSD.