Placebo psychedelics: Characteristics, side effects, and predictors

Abstract

Accumulating evidence suggests that psychedelic drugs such as psilocybin have both clinical promise and the potential to inform our understanding of the neural bases of awareness and perception (Goodwin et al., 2022, New England Journal of Medicine). Despite recent progress in our understanding of the impact of these drugs, there are lingering concerns as to whether responses to psychedelic drugs are partly driven by placebo responses (Burke & Blumberger, 2021, Nature Medicine). Indeed, preliminary research suggests that placebos can reproduce psychedelic responses, at least in part (Olson et al., 2020, Psychopharmacology). Independent research also demonstrates that verbal suggestions alone can induce a variety of mystical-type experiences (e.g., Evans & Lynn, 2021, Psychology of Consciousness). Relatedly, the prevalence of nocebo responding in response to psychedelics has been largely neglected in research to date. Finally, despite overlap in the trait variables that predict response to psychedelics, placebo, and nocebo responding (Brascher et al., 2020, Psychosomatic Medicine; Studerus et al., 2012, PLoS One), the trait variables that predict responses to a placebo psychedelic are unknown. This experiment will examine whether a compelling placebo presented as a psychedelic can elicit classic psychedelic responses on standardised psychometric measures, nocebo (side effect) responses, and altered performance in a perceptual task (temporal reproduction) known to be sensitive to the influence of psychedelics (Wittmann et al., 2007, Journal of Psychopharmacology; Yanakieva et al., 2019, Psychopharmacology). We will also examine whether placebo and nocebo responses can be predicted from a range of trait variables (responsiveness to verbal suggestion, dissociation, and trauma) that have previously been linked to placebo/nocebo responding (Corsi & Colloca, 2017, Frontiers in Psychology; Parsons et al., 2021, Psychosomatic Medicine). This work has the potential to inform our understanding of the role of placebo and nocebo effects in the response to psychedelics.

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