4 ms·

I think a major criticism of how this study is designed is that it is not truly "blinded". I doubt many of the participants were unsure if they received psilocy

I think a major criticism of how this study is designed is that it is not truly "blinded". I doubt many of the participants were unsure if they received psilocybin vs escitalopram. That being said, there are a number of studies that suggest this is an effective treatment, so I hope this can become more available to those who need it. However, for treatment resistant depression (especially with a catatonia component), intranasal ketamine is very hard to beat. Only topped by ECT in my experience.

RobotToaster 2y ago
How would you effectively blind a study on a drug with such obvious "side effects"? I can see such unreasonable objections being used to prevent it's approval though.
- keepamovin 2y ago
  That was the "reason" the FDA nuked the MDMA approval. "Unblinded because people could tell if they were on placebo or active therefore how do we know it wasn't just placebo effect based on belief" Seems spurious as: - 1) how do you reliably measure "people could tell"?; - 2) if people sensed it, likely they can sense when they are on active in a whole range of effective medicines, so seems a biased / moved-goalpost application of the "rules"; - 3) what does it matter if the strength of the drug effect is greater than the strength of the placebo? Ie, surely they can model and subtract and control, so what does it matter if the actual effect is more than placebo? Ugh...
Jerrrrrrry 2y ago
Having tried all the drugs, Ketamine and its cousins are very "preppy" - the idealization and ruminating seem to be more side-steppable; as if they were intrusive thoughts that were a minor annoyance. With the after-glow lasting weeks however, it seems to facilitate/allow a period of self-reflection (using whatever else possibly as an aide) that is notably absent of self-pity.
fullspectrumdev 2y ago
The doses of psilocybin being used were so low as to be barely perceptible.
- jdietrich 2y ago
  The participants received a 25mg dose; I can assure you that such a dose is very much perceptible. https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(24)00378-X/fulltext https://www.thelancet.com/journals/eclinm/article/PIIS2589-5...
  - fullspectrumdev 2y ago
    Ah, I made a calculation error by an entire order of magnitude while converting that to “grams of dried mushroom”. Yeah that dose you would notice a fair bit - it’s equivalent to about 2.5g dried cubes.
kjkjadksj 2y ago
Being blinded isn’t some gold standard. For example we know exercise leads to good health outcomes from unblinded studies. Every study on fitness ever done is unblinded and we consider these results to be a ground truth.
- hx8 2y ago
  The randomized controlled double-blind study is a gold standard. It solves for so many different biases. Without it the burden of proof is higher. Luckily, the evidence that exercise is healthy is so overwhelming that we have a scientific conciseness.
- dredmorbius 2y ago
  "Parachute use to prevent death and major trauma when jumping from aircraft: randomized controlled trial" (2018) <https://www.bmj.com/content/363/bmj.k5094 https://www.bmj.com/content/363/bmj.k5094>
NickM 2y ago
I think a major criticism of how this study is designed is that it is not truly "blinded". I doubt many of the participants were unsure if they received psilocybin vs escitalopram. This is already a problem for most psychiatric drug trials; studies have found that most people can tell if they’re on an SSRI or in a control group, since the side effects are pretty noticeable. There is evidence that this skews study results, to the point that some scientists believe that SSRIs may only be “effective” because the obvious side effects make them a good active placebo.

RobotToaster 2y ago

How would you effectively blind a study on a drug with such obvious "side effects"? I can see such unreasonable objections being used to prevent it's approval though.

keepamovin 2y ago
That was the "reason" the FDA nuked the MDMA approval. "Unblinded because people could tell if they were on placebo or active therefore how do we know it wasn't just placebo effect based on belief" Seems spurious as: - 1) how do you reliably measure "people could tell"?; - 2) if people sensed it, likely they can sense when they are on active in a whole range of effective medicines, so seems a biased / moved-goalpost application of the "rules"; - 3) what does it matter if the strength of the drug effect is greater than the strength of the placebo? Ie, surely they can model and subtract and control, so what does it matter if the actual effect is more than placebo? Ugh...

Jerrrrrrry 2y ago

Having tried all the drugs, Ketamine and its cousins are very "preppy" - the idealization and ruminating seem to be more side-steppable; as if they were intrusive thoughts that were a minor annoyance. With the after-glow lasting weeks however, it seems to facilitate/allow a period of self-reflection (using whatever else possibly as an aide) that is notably absent of self-pity.

fullspectrumdev 2y ago

The doses of psilocybin being used were so low as to be barely perceptible.

jdietrich 2y ago
The participants received a 25mg dose; I can assure you that such a dose is very much perceptible. https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(24)00378-X/fulltext https://www.thelancet.com/journals/eclinm/article/PIIS2589-5...
- fullspectrumdev 2y ago
  Ah, I made a calculation error by an entire order of magnitude while converting that to “grams of dried mushroom”. Yeah that dose you would notice a fair bit - it’s equivalent to about 2.5g dried cubes.

kjkjadksj 2y ago

Being blinded isn’t some gold standard. For example we know exercise leads to good health outcomes from unblinded studies. Every study on fitness ever done is unblinded and we consider these results to be a ground truth.

hx8 2y ago
The randomized controlled double-blind study is a gold standard. It solves for so many different biases. Without it the burden of proof is higher. Luckily, the evidence that exercise is healthy is so overwhelming that we have a scientific conciseness.
dredmorbius 2y ago
"Parachute use to prevent death and major trauma when jumping from aircraft: randomized controlled trial" (2018) <https://www.bmj.com/content/363/bmj.k5094 https://www.bmj.com/content/363/bmj.k5094>

NickM 2y ago

I think a major criticism of how this study is designed is that it is not truly "blinded". I doubt many of the participants were unsure if they received psilocybin vs escitalopram. This is already a problem for most psychiatric drug trials; studies have found that most people can tell if they’re on an SSRI or in a control group, since the side effects are pretty noticeable. There is evidence that this skews study results, to the point that some scientists believe that SSRIs may only be “effective” because the obvious side effects make them a good active placebo.