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.
Ketamine's rapid antidepressant effects in major depressive disorder and bipolar disorder, including treatment-resistant depression, may stem from restoring deficits in neuroplasticity. A literature search of 139 publications—from cell cultures, animal models, and patients—found accumulating evidence that ketamine increases molecules involved in neuroplasticity, paired with rapid mood improvements. Key molecules include glutamate, AMPA receptors, mTOR, BDNF/TrkB, VGF, eEF2K, p70S6K, GSK-3, IGF2, Erk, and microRNAs. The studies suggest a robust relationship between mood improvements and ketamine-induced increases in molecular neuroplasticity, especially intracellular signaling molecules.