Neuroendocrinology
October 30, 2025
Sabrina Wong, Gia Han Le, Jens Uhlig et al.
Blocking NMDA receptors improves the function and survival of pancreatic alpha and beta cells, which may help explain why certain NMDA antagonists like ketamine, esketamine, and dextromethorphan have antidepressant effects and could also address metabolic problems often seen in depression. The findings suggest a shared mechanism linking mood regulation and pancreatic hormone control. More research is needed on how low doses of these drugs affect pancreatic function and delta cells.
Canadian journal of anaesthesia = Journal canadien d'anesthesie
September 1, 2025
Mindy Lu, Victoria Tucci, Nandana D. Parakh et al.
Most patients with chronic pain at a Toronto pain clinic were willing to join a clinical trial testing MDMA-assisted therapy for pain relief. Among 42 patients surveyed, 76% expressed willingness to participate in the EASE-Pain trial, which compares MDMA with an active placebo. White/European participants were more likely to be willing than nonwilling. The main motivators were pain relief (62%) and seeking alternatives to ineffective treatments (26%). Common concerns included side effects (43%), impacts on comorbidities (19%), and stigma associated with MDMA (19%). The findings suggest that protocol modifications, such as better patient education on drug effects, may improve trial enrollment and acceptability.
Biological Psychiatry
April 9, 2025
Mary E. Kittur, L. Martínez, Brett D. M. Jones et al.
No Summary
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
February 1, 2025
Danica E. Johnson, Nelson B Rodrigues, Sydney Weisz et al.
Depression with co-occurring posttraumatic stress disorder (PTSD) leads to more severe symptoms and poorer response to standard treatments. In a retrospective analysis of 134 patients with treatment-resistant depression, four ketamine infusions (0.5-0.75 mg/kg) reduced depressive symptoms equally in those with and without comorbid PTSD; no significant group-by-time interaction was found. PTSD symptoms also significantly improved across all symptom clusters, with moderate to large effect sizes. Ketamine shows promise as an effective intervention for this hard-to-treat population, though future randomized trials should explore factors driving improvement and long-term outcomes.
The lancet. Psychiatry
May 1, 2026
Joseph J Taylor, Balázs Szigeti, Noah D Silverberg et al.
Placebo effects remain a major paradox in medical research, with more data available from placebo-controlled trials than on any treatment, yet little deep analysis of how they are measured, appraised, and interpreted. This review shifts focus from clinical practice to clinical trials, examining established and emerging approaches for managing placebo effects in randomized controlled trials. It highlights three key challenges in contemporary psychiatric research: blinding and expectancy in psychedelic trials, large placebo responses in interventional psychiatry trials (device or procedure-based treatments), and the implications of overlapping neurobiological mechanisms between placebo effects and psychiatric treatments.
CNS Drugs
October 1, 2023
Dania Akbar, Taeho Greg Rhee, Felicia Ceban et al.
A systematic review of five studies found that AXS-05, a combination of dextromethorphan and bupropion, rapidly reduces depression severity in adults with major depressive disorder who do not respond to standard antidepressants. Depressive symptoms measured on the MADRS scale decreased significantly compared to placebo as early as one week and compared to an active control at two weeks. The treatment effect was maintained for up to 12 months, with an average 23-point reduction from baseline. The therapy was well-tolerated with only transient side effects. These results support the role of glutamatergic and sigma-1 signaling pathways in depression.
Journal of Affective Disorders
December 1, 2022
Anastasia Levinta, Shakila Meshkat, Roger S McIntyre et al.
Ketamine rapidly reduces depressive symptoms in people with treatment-resistant depression, but its effectiveness may diminish as the number of prior failed treatments increases. A systematic review of 18 randomized controlled trials found that ketamine and esketamine worked at both lower and higher stages of treatment resistance, yet effect sizes and duration of benefits were greater in studies involving patients with fewer prior antidepressant failures. Variability in how studies defined treatment resistance and measured outcomes prevented clear comparisons of efficacy across different resistance stages. The authors conclude that while ketamine remains broadly effective, more failed treatment trials may reduce its efficacy, and participant-level data are needed to clarify the relationship between resistance level and response.
Journal of Affective Disorders
October 15, 2022
Isak Joneborg, Yena Lee, Joshua D. Di Vincenzo et al.
A systematic review of five randomized-controlled trials found that ketamine-assisted psychotherapy (KAP) had a significant positive effect on primary outcome measures for adults with substance use disorders and treatment-resistant depression, but the data is mixed. The single trial examining KAP for treatment-resistant depression found no benefit. The review notes a lack of large, replicated clinical trials and no studies actively examining mechanisms of action. Evidence suggests temporary neural changes caused by ketamine, such as NMDAR inhibition and increased synaptic neuroplasticity, may affect treatment outcomes. Preliminary findings also suggest adjunct psychotherapy, changes in perspective, and spirituality may play a role.