Placebo-induced Altered States of Consciousness – A Proof-of-Concept Study of a Psychedelic Placebo Intervention

Abstract

The intensity of altered states of consciousness (ASC) induced by a psychedelic represents a key mechanism underlying the therapeutic effects of psychedelic-assisted therapy (PAT). However, growing evidence suggests that expectations may contribute significantly to therapeutic effects of PAT. The present study examined whether a psychedelic placebo could induce an ASC in a PAT- analogous setting and potential influences on the intensity of this experience. Thirty-eight psychedelic-naive healthy adults were randomized to one of two experimental rooms. One room with a suggestive and comfortable design and the other with minimal furnishing. All participants received a capsaicin nasal spray presented as the psychedelic 4-HO-DET. Main outcomes were the intensity of the alteration in states of consciousness, the acute drug high, challenging experiences as well as level of dissociation. Across both rooms, participants reported ASC-related experiences significantly departing from zero across most scales, with strongest evidence for positive experience, drug liking, and desire for more (all BF10 > 10,000). No evidence supported a difference between room conditions (all BF10 < 1.5). Across exploratory regressions, no variable reliably predicted self- reported ASC intensity. Higher suggestibility (b = -0.65 95% CrI [-1.20, -0.07], pd = .985) and extraversion (b = -0.48 95% CrI [-1.00, 0.06], pd = .961) were associated with lower observer-rated dissociation. A multi-component psychedelic placebo intervention reliably induced ASCs in a PAT- analogous context, demonstrating that procedural expectations alone are sufficient for ASC induction. Room environment did not modulate experienced intensity, suggesting procedural rather than environmental components drive expectation-based ASCs.