Blinding Integrity and Psychedelic Drug Trials
Michael Elliott, Olga Chernoloz
JAMA Psychiatry August 5, 2026 DOI: 10.1001/jamapsychiatry.2026.2293 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Letter to the editor Peer reviewed |
|---|---|
| Intervention | Mebufotenin (GH001) |
| Duration | 1 week |
| Measures | Montgomery-Åsberg Depression Rating Scale (MADRS) |
| Key points | The reported effect size (d = -2.0) for mebufotenin exceeds the theoretical maximum for antidepressants, implying methodological issues may account for the results. |
Abstract
To the Editor In JAMA Psychiatry, Cubała et al. report that inhaled mebufotenin (GH001) reduced depression severity by 15.5 points more than placebo on the Montgomery-Åsberg Depression Rating Scale (MADRS) at 1 week, with 57.5% of patients achieving remission vs 0% in the placebo group. The effect size (d = −2.0) overwhelmingly surpasses those of selective serotonin reuptake inhibitors, ketamine, and promising psilocybin trials. Remarkably, it also exceeds the theoretical maximum effect size (d = 1.75) achievable by perfectly effective antidepressants under normal placebo conditions. Such effect sizes are typically seen only in state-switch interventions like penicillin resolving bacterial infections or vaccines preventing them altogether. Against that backdrop, the effect size suggests methodological factors beyond pharmacology.