Blinding and Expectancy Confounds in Psychedelic Randomised Controlled Trials

There is increasing interest in the potential for psychedelic drugs such as psilocybin, LSD and ketamine to treat a number of mental health disorders. To gain evidence for the therapeutic effectiveness of psychedelics, a number of randomised controlled trials (RCTs) have been conducted using the traditional RCT framework and these trials have generally shown promising results, with large effect sizes reported. However, in this paper we argue that estimation of treatment effect sizes in psychedelic clinical trials are likely over-estimated due to de-blinding of participants and high levels of response expectancy generated by RCT trial contingencies. The degree of over-estimation is at present difficult to estimate. We conduct systematic reviews of psychedelic RCTs and show that currently reported RCTs have failed to measure and report expectancy and malicious de-blinding. In order to overcome these confounds we argue that RCTs should routinely measure de-blinding and expectancy and that careful attention should be paid to the clinical trial design used and the instructions given to participants to allow these confounds to be estimated and removed from effect size estimates. We urge caution in interpreting effect size estimates from extant psychedelic RCTs.

The “placebo” paradox and the emotion paradox: Challenges to psychological explanation

Philosophical debates about how best to explain emotion or placebo are debates about how best to characterise and explain the distinctive form of human responsiveness to the world that is the object of interest for each of those domains of inquiry. In emotion research, the cognitive theory of emotion faces several intractable problems. I discuss two of these: the problem of epistemic deficit and the problem of recalcitrant emotions. Cognitive explanations in Placebo Studies, such as response-expectancy and belief-based explanations, also face the problem of epistemic deficit in addition to the problem of logically self-destructive true belief. While such considerations might motivate a retreat to affect, this brings its own problems. I argue that it is a particular version of cognitivism, representational cognitivism (Rep-Cog), that generates the paradoxes we encounter in emotion and placebo research. I propose that turning to nonrepresentational accounts of cognition will dissolve these paradoxes. As I move toward conclusion, I propose drawing on the ethnomethodological tradition to respecify human responsiveness to loci of significance in the lifeworld by undertaking ethnographies of members’ own situated methods for making intelligible and accountable their attitudinal and nonattitudinal responsiveness to loci of significance in their environment.

Time-Based Expectancy for Task Relevant Stimulus Features

When a particular target stimulus appears more frequently after a certain interval than after another one, participants adapt to such regularity, as evidenced by faster responses to frequent interval-target combinations than to infrequent ones. This phenomenon is known as time-based expectancy. Previous research has suggested that time-based expectancy is primarily motor-based, in the sense that participants learn to prepare a particular response after a specific interval. Perceptual time-based expectancy — in the sense of learning to perceive a certain stimulus after specific interval — has previously not been observed. We conducted a Two-Alternative-Forced-Choice experiment with four stimuli differing in shape and orientation. A subset of the stimuli was frequently paired with a certain interval, while the other subset was uncorrelated with interval. We varied the response relevance of the interval-correlated stimuli, and investigated under which conditions time-based expectancy transfers from trials with interval-correlated stimuli to trials with interval-uncorrelated stimuli. Transfer was observed only where transfer of perceptual expectancy and transfer of response expectancy predicted the same behavioral pattern, not when they predicted opposite patterns. The results indicate that participants formed time-based expectancy for stimuli as well as for responses. However, alternative interpretations are also discussed.