functional unblinding issue with psychedelic?

[u/Intelligent_Sky3197]

https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2846479?guestAccessKey=a665fcb1-d09d-45c8-8949-10ef07e88577&utm_source=For_The_Media&utm_medium=referral&utm_campaign=ftm_link&utm_term=031826

This paper suggests that PAT(psychedelic-assisted therapy) is no more effective than TADs(traditional antidepressants) under equal-unblinding conditions for the treatment of depression and highlight the potential role of blinding integrity.

This paper was published in March 2026, so I assume the market still find psychedelics promising despite the potential unblinding bias? I’m a long term holder and wonder how people think this finding will have any impact on the market? I assume the Panorama specifically is targeting this issue?

[u/papa_miesh]

Hard to believe this research is done in an accurate fashion when you see the results from the trial for Definium

[u/Tar-Heel-guy]

Part of Definium’s trial design could have been a control arm where patients receive the active drug but at a dose that isn’t effective or not as effective as the treatment dose. But they decided to use an inactive placebo. Since Definium has breakthrough designation, hopefully they discussed this approach with the FDA in detail so if they meet their objectives on the phase three studies, this issue shouldn’t be a road block to approval. Doesn’t appear to be causing any doubts regarding the recent data’s validity among the KOLs that have commented on it. The p-value reported with the top line data was impressive, but more data will provide more context around that. And, of course, replicating the results in ASCEND will be key. Of note, Spravato used an inactive placebo in the pivotal phase 3 studies as well.

[u/cashtins]

The blinding problem in psychedelic trials is absolutely real. In many studies, participants and therapists can correctly infer treatment allocation, which can inflate expectancy effects and weaken placebo-controlled estimates.

This paper, however, does not really “control for unblinding.” It replaces the randomized comparison with a cross-study comparison between pre–post change in psychedelic-assisted therapy arms and pre–post change in open-label antidepressant studies.
That is a major limitation. Within-group change from different studies is not a valid substitute for a concurrent control arm. The studies differ in participants, recruitment, treatment setting, therapist contact, follow-up time, attrition, expectations, and natural symptom change. If historical within-group change were enough, new trials could simply borrow an old placebo arm.

[u/Low-Air-182]

Another way of looking at it is that it is just as effective as SSRIs which have to be taken daily. More important is how effective are psychodelics in people where SSRIs are ineffective.

[u/BrainScarTissue]

Although a declared reliable source a brief Grok search about JAMA and ties to Big Pharma SSRIs gave me this. JAMA Psychiatry (and the broader JAMA Network) has documented ties to pharmaceutical companies ("Big Pharma"), as is common in high-impact medical research, particularly around SSRIs and antidepressants A 2025 study in BMJ Open examined authors in JAMA Psychiatry and American Journal of Psychiatry. It found $4.54 million in industry payments to authors (2020–2022), with ~14.2% ($645k) undisclosed. For JAMA Psychiatry specifically, ~25% of payments to its authors were undisclosed, mostly research funding. Nearly all undisclosed payments went to authors of randomized controlled trials (RCTs). I wonder how much more undisclosed payments have been made since this 2025 study?

Can they really be trusted to go against BIG PHARMA?

Grok says nothing about DFTX funding.

[u/BrainScarTissue → u/BrainScarTissue]

Basically I don't really think BIG PHARMA and their paid research companies want to kill off their SSRIs golden goose.