I want to highlight a finding from ( that IMO did not receive enough attention in #psychedelic trial geek circles: it shows that the #placebo effect is much smaller in psychedelic #depression trials than in trials with traditional #antidepressants (SSRIs/SNRIs). The placebo effect is ~4 points lower on the Hamilton scale (HAMD17) in psychedelic trials' placebo arm. For context, this 4 points is about twice the effect as the difference between placebo and traditional ADs. An extreme example of the lack of placebo effect in psychedelic trials is the interim analysis of a Cybin trial, where patients in the placebo group got WORSE after dosing (its a depression scale, so higher is worse; !!! I looked at the results of many-many depression trials in my life, but I do not remember seeing this anywhere else. Indeed, I checked the data from a 2021 meta analysis of traditional AD trials ( where in total 304 placebo arms were included. In all of them patients improved, showing just how odd is the result from the Cybin trial. Why is the placebo effect diminished in psychedelic trials? IMO its the 'know-cebo' effect (I think coined by @LukeJelen): the disappointment when patients realize they are in the placebo group. No patient wants to be in the control condition in any trials, but noticing it is much easier in psychedelic trials due to their intense effects. Criticisms of psychedelic trials almost always focus on potential positive expectancy in the psychedelic arms (eg. , but if we take the 'know-cebo' effect seriously, then eliminating disappointment in the control arms is just as important. How to do that? Well, I have ideas ... wait for the paper here or catch me at my next conference talk :)

👆friends, party-goers, would appreciate a retweet of the poll above, want to get up the sample size:) 🤗🙏@tommaso_barba @m_wall @mycopreneur @psy_dao @tipado @drrickbarnett @TimmyJSDavis @LiveInMushLove @microdose_io @rosmcalpine @AM_Wingert @NadiaHutten @singletonion @LarissaJMaier @gavinho @AdamAndros @dhillierwrites @MichaelHaichin @ehaijen @RachelFreire @PaulAustin3w @_MitchellGomez_ @TheBorisLab @mattbagg @MGirnNeuro @hartogsohn @ferenstein @GCampbellPsych @calyxlaw @vincepsy @PLiknaitzky @RayyanZafar6 @algekalipso @alysesue

@BrianSopko86 Haha, can relate. Been to @boomfestivalHQ in Portugal when temperate was 100f+, but my question aimed to exclude thise extreme circumstances

RT @ExistWell: Excited to announce a clinic for individuals experiencing difficulties following a psychedelic experience. I believe this is…

RT @Josh__Hardman: MAPS’ Twitter account has been hacked. It is NOT behind a crypto token which uses the MAPS name.

@BenColagiuri @katefaasse @WRief1 @Colloca_Luana @SIPSplacebo ohh, I see, will keep my eyes out for the next one. And let me know if you need something on the intersection of psychedelics and placebo/unblinding😉

@Abelaer not exactly hacker news, but it is on the front of my to-read list!

You write "Selecting the right antidepressant for melancholic depression makes a huge difference." Sounds good, but much harder to do in practice than in theory. We have been researching for decades now what patients respond to what ADs without any clear consensus. I would love to see a study where skilled/experienced clinicians select the AD for each patient and then the patient is randomized to receive either the selected AD or placebo. Would the result of this trial be much better than what we see in these trials? Given the lack of consensus regarding what ADs are best for what type of depression, I do not think so, but open to the possibility.

RT @RCarhartHarris: New study assessing the relationship between psychedelics and creative insight, coming out of our lab @UCSF. Check it o…

@igoreckert you are correct, I should have written PL response, not effect

@Agnosceptic @BellevueDoc Yeah I saw that. That study started a while ago, hope to see results soon

Traditional placebo controlled studies try to answer the question "does trt A works?" . The comparative trials you mention try to answer a different question: "does trt A works better than trt B?". Both question are legitimate

wait, I am confused. "The reason why you didn't find it reported" -> reported what? negative outcomes? I am not surprised by what you wrote, but unsure how thats related to what I wrote

@igoreckert I shared the publication where I am getting the numbers from, see first link in my post

@iainjordan this is just an interim analysis on the company's website. Probably we will see effect sizes in the publication

@KlavsPeder the issue is that nobody knows an agent that could behave as blinding placebo

@DrugCulturesPod I would sign up for that trial! :)

Yes, someone just highlighted the same on linkedin, I missed it! - "The majority of the patients treated with GH001 achieved remission with a 57.5% remission rate on Day 8 compared with 0% in the placebo group" - "GH001 led to a significant reduction from baseline of -15.2 points in Montgomery-Åsberg Depression Rating Scale (MADRS) total score on Day 8, compared with +0.3 points in the placebo group (difference of -15.5 points, p<0.0001)."

@DrugCulturesPod sign me up for that!