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Blinding Integrity and Psychedelic Drug Trials—Reply

Дата публикации: 01-10-2026 00:00:00

In Reply We thank Hsu and colleagues and Elliott and Chernoloz for their comments on our GH001 trial on treatment-resistant depression published in JAMA Psychiatry. Both letters argue that functional unblinding inflated our treatment effect through participant expectancy. Fully blinding psychedelic trials is difficult, and we agree that functional unblinding cannot be excluded as a contributor to the observed effect size. As Elliott and Chernoloz note, this does not diminish the therapeutic potential of GH001; the question raised is one of magnitude. However, the data do not support the conclusion that expectancy accounts for a large proportion. Importantly, neither letter considers the durability data. Of 23 patients in remission at day 8, 20 (87.0%) sustained remission across the 6-month assessment with infrequent retreatment. Expectancy effects are typically tied to the salience of dosing; remission sustained across 6 months is not the pattern expectancy alone would produce. Consistent with this, Szigeti et al found that pretreatment expectancy did not predict response in the psilocybin arm of a head-to-head trial against escitalopram for depression. The systematic review by Orsini et al of blinding integrity across 112 psychedelic trials similarly notes that assessment may need to integrate efficacy, reproducibility, durability, and safety. The totality of our data, including convergent improvements in Hamilton Anxiety Rating Scale (HAM-A), Clinical Global Impressions–Severity (CGI-S), and Quality of Life Enjoyment and Satisfaction Questionnaire–Short Form (Q-LES-Q-SF) rated by different blinded assessors satisfies that standard.

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