Depression and Anxiety
April 6, 2016
Chadi G. Abdallah, Thomas G. Adams, Benjamin Kelmendi et al.
204 citations
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.
SSRN Electronic Journal
January 1, 2026
Ben Kelemndi, Thomas G. Adams, Terence H. W. Ching et al.
1 citation
A single dose of psilocybin (0.25 mg/kg) produced rapid, clinically meaningful, and sustained reductions in obsessive-compulsive disorder (OCD) symptoms among adults with treatment-resistant OCD. In a randomized, double-blind, placebo-controlled trial, the psilocybin group showed a 9.76-point decrease on the A-YBOCS at 48 hours, compared to a 0.07-point increase in the niacin group. At one week, 69.2% of psilocybin participants achieved a response (≥35% symptom reduction) versus 0% of niacin participants. Benefits persisted through 12 weeks. One serious adverse event (suicidal ideation) occurred; no treatment-related deaths were reported.
February 11, 2026
Sarah Shnayder, Gabrielle Agin-Liebes, Troy Hubert et al.
preprint
In people with treatment-resistant obsessive-compulsive disorder (OCD), greater mystical-type experiences during psilocybin sessions—especially feelings of unity, sacredness, and transcendence—were linked to lower OCD symptom severity at 1-week and 12-week follow-ups, even after accounting for baseline severity and treatment condition. The Mystical subscale of the Mystical Experience Questionnaire showed the strongest and most consistent associations. The Space–Time subscale was related to lower OCD severity only at 12 weeks. Positive mood, ineffability, and challenging experiences were not significantly tied to post-treatment OCD severity. These results suggest that the quality of subjective experience during psilocybin sessions may help optimize treatment outcomes.
January 15, 2026
Benjamin Kelmendi, Thomas G. Adams, Terence H. W. Ching et al.
preprint
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.