MDMA-assisted psychotherapy shows promise as a safe and effective treatment for chronic, treatment-refractory posttraumatic stress disorder (PTSD). A systematic review and meta-analysis of five randomized trials involving 106 participants (average age 35–40 years, 70% female) found that MDMA-assisted psychotherapy produced a high rate of clinical response and remission, with a large effect size in reducing PTSD symptoms. The treatment was well-tolerated, with few serious adverse events. However, larger studies with longer follow-up are needed to confirm these findings.
In a rat model of depression, both short-term and long-term ketamine treatment alleviated depressive-like behaviors and normalized stress hormone activity. However, long-term use impaired object recognition memory and increased stereotypic behaviors, indicating potential cognitive and psychotic side effects. Ketamine boosted brain-derived neurotrophic factor (BDNF) and related signaling pathways (TrkB, Akt, GSK-3β, mTOR) while reducing markers of autophagy, tau pathology, and oxidative stress, suggesting enhanced neuronal survival and synaptogenesis. The findings indicate that ketamine's antidepressant benefits come with risks of cognitive decline and psychotic-like effects when used chronically.