Ketamine produces rapid antidepressant effects within 24 hours, thought to involve mTORC1 activation. In a double-blind crossover trial, 20 depressed patients received either rapamycin (an mTORC1 inhibitor) or placebo before ketamine. Rapamycin did not block ketamine's 24-hour antidepressant effects. Over two weeks, rapamycin prolonged ketamine's benefits: response rates were 41% with rapamycin versus 13% with placebo, and remission rates were 29% versus 7%. These findings question whether systemic or local mTORC1 blockade matters and suggest rapamycin may extend ketamine's effects, potentially informing mechanisms of depression relapse.
In a qualitative study of the first randomized placebo-controlled trial of psilocybin for treatment-refractory obsessive-compulsive disorder (OCD), interviews with 12 participants revealed four major themes: influences on the psilocybin experience (set and setting), acute effects (perceptual, metacognitive, emotional, and impact on OCD), post-dosing changes in OCD symptoms and perceptions, and post-dosing changes beyond OCD symptoms. Acute effects were often lower in intensity, possibly due to interference by OCD symptoms. Some acute and post-dosing effects mapped onto mechanisms of evidence-based psychotherapies like exposure and response prevention and acceptance and commitment therapy, suggesting potential for integrating psilocybin with structured psychotherapy for OCD.