Blinding and Expectancy Effects in Psychedelic Trials
This paper reviewed reports of of blinding and expectancy effects in psychedelic trials from 1990-2020.
Key Takeaways:
- Increasing numbers of RCTs for psychedelic drugs such as ketamine, LSD and psilocybin are being reported for a variety of disorders including depression and anxiety
- Psychedelic RCTs are likely confounded by de-blinding, which when combined with expectancy effects can cause over-estimation of effect sizes
- Extant psychedelic RCTs have generally not reported de-blinding and pre-trial expectancy
- The authors suggest trial designs and statistical approaches that might help to ameliorate these confounds
Abstract
Introduction: There is increasing interest in the potential for psychedelic drugs such as psilocybin, LSD and ketamine to treat several mental health disorders, with a growing number of randomised controlled trials (RCTs) being conducted to investigate the therapeutic effectiveness of psychedelics.
Areas covered: We review previous literature on expectancy effects and blinding in the context of psychedelic RCTs – literature which strongly suggest that psychedelic RCTs might be confounded by de-blinding and expectancy. We conduct systematic reviews of psychedelic RCTs using Medline, PsychInfo and EMBASE (Jan 1990 – Nov 2020) and show that currently reported psychedelic RCTs have generally not reported pre-trial expectancy, nor the success of blinding procedures.
Expert opinion: While psychedelic RCTs have generally shown promising results, with large effect sizes reported, 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. We suggest that psychedelic RCTs should routinely measure de-blinding and expectancy. Careful attention should be paid to clinical trial design and the instructions given to participants to allow these confounds to be reduced, estimated and removed from effect size estimates. We urge caution in interpreting effect size estimates from extant psychedelic RCTs.
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