Major depressive disorder is a common psychiatric condition that often responds poorly to traditional antidepressants, which can take weeks to work. Over the past two decades, the NMDA receptor antagonist ketamine has attracted attention because a single low dose produces rapid antidepressant effects in people with treatment-resistant depression. Evidence from animal and human studies suggests that ketamine triggers a surge of glutamate, initiating a cascade that promotes synaptogenesis and reverses stress-related damage, especially in the prefrontal cortex. This review covers the neurobiology of stress-related depression, the safety and efficacy of ketamine, its mechanism of action, and predictors of treatment response, along with research limitations and future directions.
A single dose of psilocybin (0.25 mg/kg) produced rapid and sustained reductions in obsessive-compulsive disorder (OCD) symptoms among adults with treatment-resistant OCD. In a randomized, double-blind trial, 28 adults received either psilocybin or niacin (250 mg). At 48 hours, OCD severity scores dropped by about 10 points more in the psilocybin group than in the niacin group, a large effect. At one week, 69% of psilocybin participants achieved a clinically meaningful response, compared with none in the niacin group. Benefits lasted through 12 weeks. One serious adverse event occurred. Open-label psilocybin given later also reduced symptoms. The findings suggest psilocybin may offer a new treatment approach for treatment-resistant OCD, but larger confirmatory trials are needed.