Pα+ Psychedelic Bulletin #222:: Unpacking EPIsoDE; Meta-Analysis Says Psychedelics No Better than Traditional Antidepressants; Usona’s First Patent Application Publishes

Ambitious Endpoint, Modest Results: Unpacking EPIsoDE, Germany’s Psilocybin for TRD Study

A 144-patient, two-site German study that evaluated two different doses of psilocybin versus nicotinamide in patients with treatment-resistant depression (TRD), dubbed EPIsoDE, was published this month (Mertens et al., 2026).

We covered an earlier abstract, which hinted at the results of the study, in Bulletin 220. Prior to that, we first highlighted the study’s design and a glimpse at the results following a presentation at ICPR in 2024. 

Today, we take a deeper dive into the published study and share reactions from other researchers in the field.

As a reminder, the trial administered two doses six weeks apart, with patients randomised to receive:

• “placebo (100 mg nicotinamide) followed by 25 mg psilocybin
• 5 mg psilocybin followed by 25 mg psilocybin, or
• 25 mg psilocybin followed by either 5 mg or 25 mg psilocybin”

The protocol included seven preparatory and integration psychotherapeutic sessions that each lasted up to two hours. Both study therapists—one male and one female—were present for all of a participant’s sessions. Dosing sessions lasted 6-8 hours and were followed by ...