The power of “know-cebo”: 5 Questions for data scientist Balázs Szigeti Szigeti discusses expectancy effects, unblinding, and how researchers might design better studies on psychedelics.

Got interviewed by the Microdose newsletter on the intersection of #psychedelic and #placebo research and on why psychedelic research should revisit the long forgotten Zelen design to solve the "know-cebo" problem. Enjoy!

themicrodose.substack.com/p/the-power-...

If different addictions are the just different manifestations of the same underlying condition and #psychedelics-assisted therapy addresses that condition, then it should work about the same for all forms of addictions.

Instead of making a bunch of separate #psilocybin vs #alcohol / #nicotine / #gambling / #porn #addiction trials, it would make sense to run a single trial where patients with ANY form of addiction are recruited.

History repeating: guidelines to address common problems in psychedelic science - PubMed Research in the last decade has expressed considerable optimism about the clinical potential of psychedelics for the treatment of mental disorders. This optimism is reflected in an increase in researc...

Criticisms of psychedelic trials focus on positive expectancy in the psychedelic arms (eg. tinyurl.com/3bmj7ykb), but maybe 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 :)

Why is the placebo effect diminished in psychedelic trials? IMO its the 'know-cebo' effect: the disappointment when patients realize they are in the placebo group. No patient wants to be control, but noticing it is much easier in psychedelic trials due to their intense effects.

Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis All antidepressants were more efficacious than placebo in adults with major depressive disorder. Smaller differences between active drugs were found when placebo-controlled trials were included in the...

I checked the data from a 2021 meta analysis of traditional AD trials (tinyurl.com/4am6vuyv) 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.

Cybin Announces Unprecedented Positive Phase 2 Interim Data for CYB003 in Major Depressive Disorder Meeting Primary Efficacy Endpoint with Rapid and Significant Improvements in Depression Symptoms Aft... Cybin Inc. (NYSE American:CYBN) (NEO:CYBN) (“Cybin” or the “Company”), a clinical-stage biopharmaceutical company committed to revolutionizing mental

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; tinyurl.com/3aw9j74d )!

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.

Comparative oral monotherapy of psilocybin, lysergic acid diethylamide, 3,4-methylenedioxymethamphetamine, ayahuasca, and escitalopram for depressive symptoms: systematic review and Bayesian network m... PROSPERO, CRD42023469014.

I want to highlight a finding from (tinyurl.com/37n77d9b) 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).