Molecular Psychiatry
September 7, 2022
Rebecca B Price, Nicholas Kissel, Andrew Baumeister et al.
80 citations
Ketamine given intravenously rapidly reduces depressive symptoms, with effects lasting at least a week. In an analysis of 17 randomized controlled trials with 809 participants, the benefit over placebo was larger for patients who had already failed two or more prior antidepressant trials. However, no patient-level clinical or demographic characteristics—such as age, sex, or diagnosis—could predict who would respond best, limiting the ability to personalize ketamine prescriptions. The findings confirm ketamine's broad effectiveness for depression but show that precision medicine approaches cannot yet guide treatment decisions.
The Lancet
February 11, 2023
Florence Butlen‐ducuing, Drummond E-Wen Mcculloch, Marion Haberkamp et al.
28 citations
No Summary
JAMA Network Open
July 30, 2025
Fredrik Hieronymus, Evana López, Helena Werin Sjögren et al.
21 citations
In clinical trials for depression, patients given a placebo or control treatment in psilocybin trials showed significantly less improvement in depression ratings than those given control treatments in trials of SSRIs or esketamine. The meta-analysis of 17 trials found that control treatment response rates in SSRI trials were 14 percentage points higher than in psilocybin trials, and in esketamine trials were 23 percentage points higher. Dropout rates were similar for psilocybin and esketamine (5-12% active, 8-11% control) but much lower than for SSRIs (32% active, 35% control). These results suggest that psilocybin's antidepressant efficacy may be overestimated compared to SSRIs and esketamine.
Neurosci Appl
January 11, 2024
Drummond E-Wen McCulloch, Matthias E. Liechti, Kim PC. Kuypers et al.
10 citations
Psychedelic drugs like psilocybin and LSD are being tested in clinical trials for psychiatric and neurological conditions, with phase 2 studies showing particular promise for depression. At a 2023 European College of Neuropsychopharmacology meeting, experts identified key knowledge gaps that need addressing for successful medical implementation. These include understanding how these drugs work in the body (pharmacokinetics and pharmacodynamics), comparing different psychedelics, exploring the link between the duration of subjective effects and therapeutic outcomes, studying polypharmacology, and assessing the role of psychological support. The article also presents perspectives from the European Medicines Agency and Health Technology Assessors on what is most needed for medical adoption in Europe.
Neuroscience applied
January 1, 2024
Drummond E-Wen Mcculloch, Juan Pablo Lopez, Christina Dalla et al.
2 citations
Classical psychedelic drugs like psilocybin and LSD stimulate the serotonin 2A receptor and are being investigated for clinical effects in brain disorders. Experts at the ECNP 'New Frontiers meeting' in March 2023 identified key knowledge gaps in psychedelic mechanisms, including the need for appropriate behavioral models, dose optimization, molecular mechanisms, sex differences, and effects on neurotransmitter release and brain activity. The meeting highlighted the importance of preclinical and neuroimaging research to address these gaps.
JAMA Network Open
May 15, 2026
Hampus Yngwe, Pontus Plavén-sigray, Carl Johan Ekman et al.
1 citation
A single 25 mg dose of psilocybin, combined with psychotherapeutic support, produced rapid antidepressant effects in people with moderate to severe recurrent major depressive disorder. Depressive symptoms, measured by the Montgomery-Åsberg Depression Rating Scale, improved significantly more in the psilocybin group than in the placebo group by day 8, with benefits lasting through day 42 but not at one year. Self-reported depressive symptoms showed improvement as early as day 2 and persisted for over three months. The treatment was generally well tolerated, though two participants experienced persistent severe anxiety requiring medical attention. These findings suggest psilocybin may offer a rapid and relatively durable antidepressant effect.
Molecular Psychiatry
July 8, 2026
Granville J. Matheson, Johan Lundberg, Martin Gärde et al.
The serotonin 1B receptor (5-HT1BR) can be imaged in living humans using a PET tracer called [11C]AZ10419369 and is linked to major depressive disorder (MDD) and its treatment. Ketamine and electroconvulsive therapy (ECT) are rapid-acting antidepressants that raise serotonin levels, but whether they directly alter serotonin receptors was unclear. Reanalyzing 222 PET scans from three centers—including MDD patients before and after ketamine (19 completers), saline placebo (10), or ECT (13 completers)—using a hierarchical Bayesian method, the authors demonstrate large increases in 5-HT1BR binding after both ketamine (6.4%, 95% CI: 3.1–9.6%) and ECT (9.3%, 95% CI: 4.3–14.2%).
Neuropsychopharmacology
July 7, 2026
Wojciech Pasławski, D Doyon, Carl Johan Ekman et al.
Psilocybin, a rapid-acting antidepressant, reduces levels of the neuropeptide galanin and noradrenaline in cerebrospinal fluid, suggesting that normalization of these co-transmitters is a key pharmacodynamic effect. This finding comes from a secondary analysis of a randomized, placebo-controlled trial with multimodal biomarker measurements. The results indicate a selective effect of psilocybin on these specific neurotransmitters, offering insight into its mechanism of action in major depressive disorder.
BMC medical education
April 9, 2026
Nikita Sanati Morel, Dea Siggaard Stenbæk, Johan Lundberg et al.
Nine nurses completed a 15-week online and on-site training program to serve as facilitators in a trial of psilocybin treatment for depression in cancer patients. Subjective evaluations indicated the training supported knowledge and skill acquisition, but most nurses reported needing additional practical in-person training to feel adequately prepared. An objective assessment of verbal relational skills using role-plays showed a significant increase in only one of twelve measures, with medium to large effect sizes for six measures from pre- to post-training. The training model showed modest potential to improve outcomes, though effects were limited to role-play. The specific skills and qualifications needed for providing psychotherapeutic support in psilocybin treatment remain unclear.