Ketamine given intravenously rapidly reduces depressive symptoms, with effects lasting at least a week. In an analysis of 17 randomized controlled trials with 809 participants, the benefit over placebo was larger for patients who had already failed two or more prior antidepressant trials. However, no patient-level clinical or demographic characteristics—such as age, sex, or diagnosis—could predict who would respond best, limiting the ability to personalize ketamine prescriptions. The findings confirm ketamine's broad effectiveness for depression but show that precision medicine approaches cannot yet guide treatment decisions.
A systematic review of 43 pharmacological trials found that psychedelics such as MDMA, psilocybin, LSD, DMT/ayahuasca, and cannabis generally produce detrimental or neutral effects on cold cognition—non-emotionally charged cognitive functions like attention, memory, and executive function—during peak drug effects, though MDMA improved psychomotor function in some cases. The review included mostly healthy subjects, with only one study on MDMA in PTSD patients and none in major depressive disorder. Small sample sizes and inconsistent methods across studies prevent firm conclusions about whether psychedelics enhance, impair, or leave cognition unchanged. Future research should assess both acute and long-term cognitive effects as psychedelics become available for psychiatric treatment.