8 ms·

The comparison condition was psilocybin or diphenhydramine (Benadryl), and both groups got addiction counseling. >Participants correctly guessed their treatmen

The comparison condition was psilocybin or diphenhydramine (Benadryl), and both groups got addiction counseling. >Participants correctly guessed their treatment assignment in 93.6% of the first sessions, reporting a mean (SD) certainty of 88.5% (23.2%). In the second session, 94.7% guessed correctly, and mean (SD) certainty was 90.6% (21.5%). Study therapists correctly guessed treatment 92.4% of the time for first sessions and 97.4% for second sessions, and their mean (SD) certainties were 92.8% (16.3%) and 95.4% (2.9%), respectively. This is not a criticism, as these trials are very hard to blind, but as you can see in hindsight they could as well have not bothered with blinding at all. So we need to interpret this as a randomized but unblinded trial. The researchers are well aware of this, and I suspect it will inform the next steps of their research. >Several limitations of the study warrant discussion. First, diphenhydramine was ineffective in maintaining the blind after drug administration, so biased expectancies could have influenced results. Control medications such as methylphenidate,42 niacin,2 and low-dose psilocybin1 likewise did not adequately maintain blinding in past psilocybin trials, so this issue remains a challenge for clinical research on psychedelics.

radicaldreamer 4y ago
It's going to be incredibly hard to blind a study on psychedelics due to their unique and powerful effects... the best might be some sort of VR experience with a dissociative to mimic a psychedelic experience, but even that seems unlikely to be an effective control.
- TylerE 4y ago
  Especially when dealing with addiction. In other contexts, a fairly strong sedative is frequently used as the control, which is going to be a lot less subtle.
hn_throwaway_99 4y ago
Yeah, this was what I was thinking as well, but I think researchers should just accept that blinding is fundamentally impossible in studies like this: 1. With a high dose of shrooms, you're definitely going to know whether you were tripping or not. 2. If they can find another agent that mimics the effect of tripping, well then it's not really a placebo anymore.
- deleted 4y ago
  [deleted]
roughly 4y ago
Something that's going to be interesting with psychedelics and psychedelic research is that a lot of this sort of research seems to try to "control for" the phenomenological experience in favor of focusing on the biochemical mechanism of action - I think it's possible that the phenomenological experience _is_ the mechanism of action for these substances, that the actual experience of the trip is what makes the difference.
- _yb2s 4y ago
  > I think it's possible that the phenomenological experience _is_ the mechanism of action for these substances, that the actual experience of the trip is what makes the difference. I was really confused about the entire concept of blinding a study like this until I read your comment... Now I realize they are indeed proceeding from the assumption that the phenomenological experience is somehow distinct from the mechanism of action. That seems really unlikely to me- these drugs are unique because of the phenomenological experience! It seems self evident that this experience is the reason for therapeutic effects. Imagine the absurdity of trying to design a study blinding the effects of meditation for example. Meditation has measurable benefits, but what are the chances those aren't caused by the psychological effects of experiencing meditation?
  - rfrey 4y ago
    It's self evident to you that there's no effect on brain chemistry that accompanies the experience? A change that could have an impact on the condition? You might be right, maybe you're even probably right, but it's not self evident to me.
    - stocknoob 4y ago
      “Chemical imbalance” antidepressants take weeks of ~100 milligram tablets to take effect. (Nobody can quite explain what the imbalance was to begin with, and what the ideal levels are…) Psychedelics have an impact at the microgram range, with a single dose. They could be hundreds of thousands of times more potent, or, it could be the experience.
paraph1n 4y ago
There's still a difference between "guessing" correctly versus actually knowing the truth. It's different from an actually unblinded study even if participants can "guess" correctly.
- pessimizer 4y ago
  Looks to be a vanishingly small difference if they guessed correctly, the first time they were asked, 94.7% of the time with 90% confidence.
  - paraph1n 4y ago
    In order to understand the difference, you'd have to have a blinded and unblinded study, and compare the results. Then you could understand the difference between a guess with 90% confidence and actually knowing what treatment you received with certainty. It seems reckless to presume the difference (between blinded and unblinded) is small. The numbers you cite (94.7% and 90% confidence) have nothing to do with the question you're trying to answer. For example, an important difference may be with respect to expectations. If you're told you're receiving a psychedelic treatment, you may go into the experience with different expectations than if you were unsure about what treatment you were getting.
anigbrowl 4y ago
Good point. I can see the normal approach being valuable if studying microdosing, but regular dosing is going to go from 'hmm I wonder if anything will happen' to 'woohoo space llamas' in no uncertain terms. One wonders why even tried this approach, other than satisfying funding and review bureaucrats that prefer not to think.
colechristensen 4y ago
You absolutely cannot blind a psychadelic study unless you are testing psychedelics against each other or different doses. No more than you could test someone’s performance while drunk against a sober person. The effects are just invited to everybody.
cameronh90 4y ago
I didn't see it in the paper, but I wonder what the difference was in people who correctly guessed their treatment assignment between the different arms. I would imagine that everyone who got psilocybin guessed correctly.
philshem 4y ago
Reminds me of the 1962 “Good Friday Experiment” https://en.wikipedia.org/wiki/Marsh_Chapel_Experiment https://en.wikipedia.org/wiki/Marsh_Chapel_Experiment
geokon 4y ago
if the intention is to have a blind test, is there a reason it's not administer while the patient is asleep? If you stay up for 48 hours, go to sleep, get a random injection after an hour or two, wake up ~10 hours later. I would think you'd probably cut that ~90% down significantly

radicaldreamer 4y ago

It's going to be incredibly hard to blind a study on psychedelics due to their unique and powerful effects... the best might be some sort of VR experience with a dissociative to mimic a psychedelic experience, but even that seems unlikely to be an effective control.

TylerE 4y ago
Especially when dealing with addiction. In other contexts, a fairly strong sedative is frequently used as the control, which is going to be a lot less subtle.

hn_throwaway_99 4y ago

Yeah, this was what I was thinking as well, but I think researchers should just accept that blinding is fundamentally impossible in studies like this: 1. With a high dose of shrooms, you're definitely going to know whether you were tripping or not. 2. If they can find another agent that mimics the effect of tripping, well then it's not really a placebo anymore.

deleted 4y ago
[deleted]

roughly 4y ago

Something that's going to be interesting with psychedelics and psychedelic research is that a lot of this sort of research seems to try to "control for" the phenomenological experience in favor of focusing on the biochemical mechanism of action - I think it's possible that the phenomenological experience _is_ the mechanism of action for these substances, that the actual experience of the trip is what makes the difference.

_yb2s 4y ago
> I think it's possible that the phenomenological experience _is_ the mechanism of action for these substances, that the actual experience of the trip is what makes the difference. I was really confused about the entire concept of blinding a study like this until I read your comment... Now I realize they are indeed proceeding from the assumption that the phenomenological experience is somehow distinct from the mechanism of action. That seems really unlikely to me- these drugs are unique because of the phenomenological experience! It seems self evident that this experience is the reason for therapeutic effects. Imagine the absurdity of trying to design a study blinding the effects of meditation for example. Meditation has measurable benefits, but what are the chances those aren't caused by the psychological effects of experiencing meditation?
- rfrey 4y ago
  It's self evident to you that there's no effect on brain chemistry that accompanies the experience? A change that could have an impact on the condition? You might be right, maybe you're even probably right, but it's not self evident to me.
  - stocknoob 4y ago
    “Chemical imbalance” antidepressants take weeks of ~100 milligram tablets to take effect. (Nobody can quite explain what the imbalance was to begin with, and what the ideal levels are…) Psychedelics have an impact at the microgram range, with a single dose. They could be hundreds of thousands of times more potent, or, it could be the experience.

paraph1n 4y ago

There's still a difference between "guessing" correctly versus actually knowing the truth. It's different from an actually unblinded study even if participants can "guess" correctly.

pessimizer 4y ago
Looks to be a vanishingly small difference if they guessed correctly, the first time they were asked, 94.7% of the time with 90% confidence.
- paraph1n 4y ago
  In order to understand the difference, you'd have to have a blinded and unblinded study, and compare the results. Then you could understand the difference between a guess with 90% confidence and actually knowing what treatment you received with certainty. It seems reckless to presume the difference (between blinded and unblinded) is small. The numbers you cite (94.7% and 90% confidence) have nothing to do with the question you're trying to answer. For example, an important difference may be with respect to expectations. If you're told you're receiving a psychedelic treatment, you may go into the experience with different expectations than if you were unsure about what treatment you were getting.

anigbrowl 4y ago

Good point. I can see the normal approach being valuable if studying microdosing, but regular dosing is going to go from 'hmm I wonder if anything will happen' to 'woohoo space llamas' in no uncertain terms. One wonders why even tried this approach, other than satisfying funding and review bureaucrats that prefer not to think.

colechristensen 4y ago

You absolutely cannot blind a psychadelic study unless you are testing psychedelics against each other or different doses. No more than you could test someone’s performance while drunk against a sober person. The effects are just invited to everybody.

cameronh90 4y ago

I didn't see it in the paper, but I wonder what the difference was in people who correctly guessed their treatment assignment between the different arms. I would imagine that everyone who got psilocybin guessed correctly.

philshem 4y ago

Reminds me of the 1962 “Good Friday Experiment” https://en.wikipedia.org/wiki/Marsh_Chapel_Experiment https://en.wikipedia.org/wiki/Marsh_Chapel_Experiment

geokon 4y ago

if the intention is to have a blind test, is there a reason it's not administer while the patient is asleep? If you stay up for 48 hours, go to sleep, get a random injection after an hour or two, wake up ~10 hours later. I would think you'd probably cut that ~90% down significantly