Expectancy in placebo-controlled trials of psychedelics: if so, so what?

Modern psychedelic research remains in an early phase, and the eventual introduction of psychedelics into clinical practice remains in doubt. In this piece, we discuss the role of blinding and expectancy in psychedelic trials, and place this in a broader historical and contemporary context of blinding in trials across the rest of healthcare. We suggest that premature and uncritical promotion ('hype') of psychedelics as medicines is not only misleading, but also directly influences participant expectancy in ongoing psychedelic trials. We argue that although psychedelic trials are likely to significantly overestimate treatment effects by design due to unblinding and expectancy effects, this is not a unique situation. Placebo-controlled RCTs are not a perfect fit for all therapeutics, and problems in blinding should not automatically disqualify medications from licencing decisions. We suggest that simple practical measures may be (and indeed already are) taken in psychedelic trials to partially mitigate the effects of expectancy and unblinding, such as independent raters and active placebos. We briefly suggest other alternative trial methodologies which could be used to bolster RCT results, such as naturalistic studies. We conclude that the results of contemporary placebo-controlled RCTs of psychedelics should neither be dismissed due to imperfections in design, nor should early data be taken as firm evidence of effectiveness.

Automated summary

This article discusses the role of blinding and expectancy in psychedelic trials, and places it in the context of trials in healthcare. The premature and uncritical promotion of psychedelics as medicines is misleading and influences participant expectancy in ongoing trials. While psychedelic trials may overestimate treatment effects due to unblinding and expectancy effects, placebo-controlled RCTs are not perfect for all therapeutics. Practical measures such as independent raters and active placebos can mitigate the effects, and alternative trial methodologies like naturalistic studies can be considered to bolster RCT results.