The New England journal of medicine
November 3, 2022
Guy M Goodwin, Scott T Aaronson, Oscar Alvarez et al.
1,095 citations
A single 25 mg dose of psilocybin, but not 10 mg, reduced depression scores more than a 1 mg control dose over three weeks in adults with treatment-resistant depression. In this phase 2 trial, 233 participants were randomly assigned to 25 mg, 10 mg, or 1 mg of synthetic psilocybin with psychological support. The 25 mg group showed an average 12-point drop on the MADRS depression scale versus a 5.4-point drop in the 1 mg group, a significant difference. The 10 mg group did not differ significantly from control. Response and remission rates at three weeks supported the primary result, but sustained response at 12 weeks was not significantly different.
Nature medicine
July 24, 2025
Luke A Jelen, David J Lythgoe, James M Stone et al.
29 citations
Blocking the opioid system with naltrexone reduced both the brain glutamate response and the antidepressant effect of ketamine in adults with major depressive disorder. In a double-blind crossover study of 26 adults, naltrexone before ketamine infusion attenuated the rise in glutamate+glutamine relative to N-acetylaspartate in the anterior cingulate cortex and lessened the drop in depression scores the next day. The opioid system modulates ketamine's acute brain effects and subsequent mood improvement, suggesting interactions between glutamate and opioid systems may inform new depression treatments.
BJPsych open
May 10, 2024
Luke A Jelen, Rupert McShane, Allan H Young
7 citations
Ketamine shows promise for treatment-resistant depression, but its use requires careful management through evidence-based guidelines. The editorial emphasizes the need for comprehensive protocols to oversee both licensed and off-licence ketamine formulations, referencing recent efforts to develop such guidelines in New Zealand. It advocates for national registries to monitor ketamine therapy, ensuring responsible and effective treatment for depression.
The American journal of psychiatry
June 1, 2026
Luke A Jelen, Owen O'Daly, Fernando O Zelaya et al.
2 citations
Ketamine increased blood flow in specific brain regions (subgenual, pregenual, and dorsal anterior cingulate cortices) in adults with major depressive disorder, and this effect was not blocked by the opioid blocker naltrexone. However, naltrexone did disrupt the relationships between blood flow changes and both acute subjective effects and antidepressant response. The blood flow changes aligned with patterns of opioid and glutamate receptor distribution, suggesting that ketamine's effects involve interactions among multiple neurotransmitter systems.