Psychedelic trials rarely check whether participants could tell what they got, so effects may be overstated
A review of psychedelic trials from 1990 to 2020 found they generally did not report expectations before treatment or whether blinding held. The authors argue effect sizes are likely over-estimated and urge caution.
Reasonable evidence with real limitations. how we score evidence
Caveat on this rating: A methods critique: it argues effects are overstated but does not measure by how much, and it does not show the drugs have no effect. Read from the abstract only.
One paper that speaks to every full-dose psychedelic trial in this library: can a trial of a drug that causes hallucinations really be blind?
Significant findings
Muthukumaraswamy, Forsyth and Lumley reviewed the literature on expectancy effects and blinding, then ran systematic reviews of psychedelic randomised trials in Medline, PsycInfo and EMBASE from January 1990 to November 2020. The abstract names psilocybin, LSD and ketamine as the drugs of interest.
They found that "currently reported psychedelic RCTs have generally not reported pre-trial expectancy, nor the success of blinding procedures." Earlier literature, they write, "strongly suggest[s] that psychedelic RCTs might be confounded by de-blinding and expectancy."
Their view: "we argue that treatment effect sizes in psychedelic RCTs are likely over-estimated due to de-blinding of participants and high levels of response expectancy." They recommend that trials "routinely measure de-blinding and expectancy", design instructions to reduce these confounds, and they "urge caution in interpreting effect size estimates from extant psychedelic RCTs."
The other direction
The authors do not say the drugs do nothing. They write that psychedelic trials "have generally shown promising results, with large effect sizes reported." Their claim is about size and certainty: part of the reported effect may be expectation, and most trials did not measure how much. A trial where people guess their group can still find a real drug effect; it just cannot show how large it is. The psilocybin, LSD (MM120) and psilocybin-for-alcohol trials in this library are the kind of evidence this paper is about, and each reads better beside it.
What this does not show
It is a review and an argument, not a new trial. It does not test any drug. Nothing here says anyone should seek out or avoid a psychedelic treatment.
Worth asking
In the trial behind a psychedelic treatment I am reading about, did they check whether people could guess which group they were in?
Source
Blinding and expectancy confounds in psychedelic randomized controlled trials — Muthukumaraswamy SD, Forsyth A, Lumley T (2021)
Reputable peer-reviewed journal
Read the source: https://doi.org/10.1080/17512433.2021.1933434
DOI: 10.1080/17512433.2021.1933434
How this was scored
- Study design
- Systematic review of randomised trials
- Funding
- Funding not disclosed
- Published in
- Reputable peer-reviewed journal
- Sample size
- not recorded
- Preregistered
- not recorded
- Conflicts disclosed
- not recorded
- Independent of proponent
- not recorded
- Retracted
- No
Read the full scoring rubric, including what it can't tell you.
Published October 2, 2026.
Questions
How strong is the evidence behind this?
veisund rates this source "moderate evidence". Reasonable evidence with real limitations. It scores 62 out of 100 on our published rubric. One caveat travels with that badge: A methods critique: it argues effects are overstated but does not measure by how much, and it does not show the drugs have no effect. Read from the abstract only. The score is calculated from recorded facts about the source — study design, funding, publication venue, sample size, preregistration — not typed in by an editor.
What is the source for this?
Blinding and expectancy confounds in psychedelic randomized controlled trials — Muthukumaraswamy SD, Forsyth A, Lumley T (2021). Published in: Reputable peer-reviewed journal. DOI: 10.1080/17512433.2021.1933434. The full source is linked on this page so you can read it yourself.
Who paid for this research, and does that matter?
Study design: Systematic review of randomised trials. Funding: Funding not disclosed. Independence from the proponent is not recorded. Industry sponsorship is one of the most reliably measured biases in medicine, which is why funding carries real weight in the score rather than sitting in a footnote.
Is this medical advice?
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.