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Lea Mertens @leamert.bsky.social · 18/04/2026

Agreed - and despite relevant levels of functional unblinding, it is still not an open-label study. You play with expectations and uncertainty was induced.

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Lea Mertens @leamert.bsky.social · 18/04/2026

Because we were facing strict word limitations, important results had to be placed in the supplement; same for the abstract. It wasn’t our preferred way and we did our best to still acknowledge respective findings as prominently as possible.

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Lea Mertens @leamert.bsky.social · 17/04/2026

I would be curious - how would you study psychedelic treatments? Which study designs would you recommend considering the evident blinding difficulties?

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Lea Mertens @leamert.bsky.social · 17/04/2026

Result: It didn't sufficiently. This is very explicitly discussed in the manuscript. We argue that our findings underscore the difficulty of RCTs and blinding with psychedelics and maybe even challenge the feasibility of RCTs.

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Lea Mertens @leamert.bsky.social · 17/04/2026

Agreed, that's a tough one. To explain: By design, the study is a triple-blind RCT, hence it is described as such. One objective of the trial was in fact to investigate whether the 3-arm design and our two comparators (nicotinamide and low-dose/5 mg psilocybin) would improve blinding.

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Lea Mertens @leamert.bsky.social · 20/03/2026

We powered with regard to response but otherwise absolutely correct. The study was planned in 2018-2019 when only large effect sizes from open label studies were available. So agreed, definitely power issue. Today we know better.

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Lea Mertens @leamert.bsky.social · 19/03/2026

We argue in the manuscript, that we overestimated the effect size, resulting in the study being underpowered to show a significant effect on the dichotomized outcome "response" at W6, albeit showing a strong effect at W1 (34% vs. 10% vs. 6%) for instance.

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Lea Mertens @leamert.bsky.social · 19/03/2026

Absolutely, agreed - that's why Table 2 (and 3) are very helpful for grasping the results in their entirety. We see strong evidence for H1 for the majority of outcomes, especially the ones using HAMD17/BDI-II change from baseline as metric.

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Lea Mertens @leamert.bsky.social · 19/03/2026

Our pre-defined confirmatory testing procedure is outlined in our SAP (suppl 2), together with a comprehensive outline of required adaptations made during peer-review (suppl 3).

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Lea Mertens @leamert.bsky.social · 19/03/2026

The exploratory nature of those secondary endpoints in face of a negative primary endpoint is clearly stated throughout the manuscript. Additional secondary/exploratory outcomes are only reported with 95% CIs, no p-values.

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Lea Mertens @leamert.bsky.social · 19/03/2026

Due to the negative outcome on the primary endpoint, no further formal/confirmatory testing was performed on secondary outcomes. Hence, tests referring to key secondary outcomes are reported by nominal uncorrected p-values and are therefore not confirmatory evidence.

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Lea Mertens @leamert.bsky.social · 19/03/2026

We transparently report all those outcomes in the manuscript or the supplement - see the extensive Tables 3 and 4.

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Lea Mertens @leamert.bsky.social · 19/03/2026

This makes the trial inconclusive and difficult to interpret, but there is a clear signal of antidepressant efficacy worth investigating further. So yes - inconclusive from a confirmatory clinical trial framework can indeed still mean promising when looking at the full data.

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Lea Mertens @leamert.bsky.social · 19/03/2026

Appreciate the point - rigorous, well-conducted trials are essential for the field. To directly comment: The trial shows a negative result on the primary outcome (HAMD17 response at W6), but a positive result on equally relevant pre-defined secondary outcomes (HAMD17 change from baseline at W6).

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Lea Mertens @leamert.bsky.social · 18/03/2026

Excited to share our study on the Efficacy and Safety of Psilocybin in Treatment-Resistant Depression (EPISODE) - now published in @jamapsychiatry.com A negative effect on primary outcome, but evidence for a relevant antidepressant effect of 25 mg psilocybin with psychotherapy in TRD.

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Reposted by Lea Mertens

Max Wolff @trpwolff.bsky.social · 10/10/2025

New long-read theory paper in Psychological Review: Im short, we propose that effective psychedelic therapy employs the uniquely context-dependent effects of psychedelic drugs to engage & augment the same psychological change processes that underlie all effective psychotherapies. Full text below ⬇️

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Lea Mertens @leamert.bsky.social · 10/10/2025

Goodbye lake como and thank you for a wonderful break after an intense few months of data analysis, paper writing and preparing for my final psychotherapy license exam. Now off to #ECNP2025, where I will be presenting the results of our episode study on Saturday. Meet me at poster PS01-0249!

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Reposted by Lea Mertens

Max Wolff @trpwolff.bsky.social · 16/06/2025

Reframing Psychedelic Regulation: Tools, not Treatments In this new article, we propose to regulate psychedelics as psychotherapeutic treatment tools rather than as treatments in their own right. The use of anesthetics as treatment tools in surgery is a useful analogy.

Drug Science, Policy and Law
Screenshot of title page and abstract

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Reposted by Lea Mertens

josh hardman @josh-hardman.bsky.social · 31/07/2025

BREAKING: German regulators have green-lit the EU's first psilocybin compassionate access program. Unlike other countries’ pre-approval pathways, Germany’s does not require case-by-case regulatory approval and may see insurers cover costs. Details: psychedelicalpha.com/news/germany...

psychedelicalpha.com

Germany Establishes EU’s First Psilocybin Compassionate Access Program - Psychedelic Alpha

Germany has become the first EU country to allow legal access to psilocybin under a compassionate use program for treatment-resistant depression. Unlike other countries’ pre-approval pathways, Germany...

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Lea Mertens @leamert.bsky.social · 08/12/2024

Glad to be at #ACNP2024 in Phoenix! On Monday, I will be presenting the results of our episode trial in the session „Psychedelic-assisted Psychotherapy: From preclinical mechanisms to clinical applications“ alongside @fredbarrettphd.bsky.social, @kellietamashiro.bsky.social and Jennifer Mitchell.

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