The unblinding point makes sense to me. Does that collapse the two indirectness points into one point though? Is there another proposed mechanism of action for not-representativeness affecting how the results apply to the general population that would apply even though MAPS showed minimal difference
You mention that the high prior use of MDMA influenced your grade assessment. I’m curious if you took into consideration the MAPS report (www.fda.gov/media/179062...; page 81) that mentions that prior use of MDMA barely affected their phase III results.
The intervention doses for the two Mitchell studies might not be right on www.metapsy.org/sypres/mdma-.... The studies used roughly 120+60 IIRC, but metapsy reports 120.
Additionally, the group that had two 25mg sessions didn’t show any advantage over one 25mg session, so it looks like one psilocybin session adds durable benefit but another session doesn’t add anything more.
This advantage seems to disappear at the endpoint after session 2 because the other groups also take 25mg psilocybin and catch up to the group that had 25mg in session 1.
I wasn’t talking about the primary endpoint. If you look at Figure 2 you can see that 25mg psilocybin appears to have a large, statistically significant advantage over placebo after session 1.
My reading is that psilocybin did outperform placebo, but more than one psilocybin dose didn't add anything. So after the first session, the psilocybin has an advantage, then everything comes out equal at the end because the other groups also take psilocybin and catch up.
You can say the same thing about humans. Given that no one really understands what consciousness is, there is no extraordinary evidence that humans are conscious, and there is no reason that humans require consciousness to have their neural networks function and output speech.
I feel skeptical about any under/over diagnosis discussion for a construct that both hitop and doi.org/10.31234/osf... suggest is not a distinct entity, but rather a hodgepodge collection of symptoms. How can under/over diagnosis have any rigorous meaning in such a case.
The only information they have is the paragraph talking about blinding assessment in the publication.
It's not in the supplemental data and I didn't find any reference on the web to that being a standard questionnaire.
For reference, the Methylone study participants correctly guessed they got methalone (70%) or placebo (53%). That’s much less than MAPP2: MDMA (93%); placebo (75%). But that's not corrected for the differences in measurement.
The “got placebo” bin in the methylone study was also wider than their “got methylone” bin. It seems weird to have a lopsided scale. MAPP2 was symmetric.
I noticed that too and dug in more:
Blinding might not be comparable: the methylone study had a wider middle bin of “unsure” responses than MAPP2. The methylone study also didn’t report the details of the middle bin; responses could have been lopsided.
Measuring therapeutic effect is also tricky because of the “it feels worse before it gets better” destabilization phase in therapy. Destabilization predicts better long-term outcomes (10.1080/10503307.2019.1633484). Participants's stories might shed light on how this influenced the results.
I’d love to know what was happening from the participants’ perspective. I presume they are doing memory reconsolidation since the trial reports persistent improvements. Did they have psychotherapeutic intent? MR not infrequently happens on MDMA when people aren’t using it for escapism.
Interesting: The change in CAPS-5 was similar to the MDMA results from MAPP2 even though the methylone trial didn’t include therapy. SDS improvements favored methylone.
I wasn't sure what you were presenting it as an example of. :P
The depression and anxiety diagnoses falsely communicated to me that my issues didn't have a known etiology and cure.
I also found the diagnoses given to me as an adult (depression and anxiety) unacceptable myths once I realized my symptoms were simply maladaptive implicit memories learned during the period of abuse that I could permanently unlearn with memory reconsolidation.
I think the illness myth given to me was severely harmful and untrue. My parents were emotionally abusing me. A psychiatrist diagnosed me with ADHD, and my family bought into that as a way to avoid the real issue. ADHD was an acceptable myth to them; their abusive behavior was not.
Quite evocative! Do you feel that that metaphor was a helpful or unhelpful myth?
Yea...sigh
This just reminded me to actually read Benish. Ever since I read Luck's description of the illness myth I've been thinking that it might describe a large fraction of current practice and research across the different fields of mental health.
I want PVT to go away so bad. Even the academic literature on tonic immobility, freeze, and fight-or-flight is filled with the nonsense.
This is by far the best explanation of why polyvagal theory is popular that I've come across: alyssaluck.com/polyvagal-th...
It reminds me how when people become practiced enough at meditating, it's easy to notice how perceptions all pop into existence and then disappear at roughly brain wave frequencies.
Is there a recording?
I noticed when they described fear extinction in the paper it seemed like they were actually describing memory reconsolidation since they called it unlearning. I've noticed this pattern in a lot of places; people seem to call both phenomena fear extinction.
The LLM models they looked at are all old crappy ones compared to the current batch. AI moves so fast that by the time a paper is out, the results are out of date.
