Tripping on context: Characteristics and predictors of placebo and nocebo psychedelic effects

Context alone can produce psychedelic-like effects, even without an active drug. In a placebo experiment, 78 healthy participants inhaled inert medical air. When told it was nitrous oxide, they reported increased altered states of consciousness, ego dissolution, dissociation, and side effects, compared to when the gas was correctly identified as air. Time perception was not significantly affected. The strength of placebo-induced effects was predicted by individual traits of responsiveness to verbal suggestion and absorption. These results demonstrate that the context of drug administration plays a causal role in shaping psychedelic experiences.

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Abstract

Psychedelic drugs are emerging as potentially efficacious tools for treating psychiatric conditions and probing the neural basis of consciousness. Although drug administration context is widely believed to shape psychedelic effects, it remains unclear whether it can independently generate placebo and nocebo effects resembling psychedelic experiences and side effects. In a pre-registered experiment, 78 non-clinical participants inhaled inert medical air under placebo and control conditions while completing a time perception task and a resting-state period. In the placebo condition, the gas was presented as nitrous oxide, whereas in the control, it was correctly identified. Placebo administration increased altered states of consciousness, ego dissolution, dissociation, and side effects, but did not significantly impact time perception. Predictive modelling indicated that placebo-induced psychedelic effects were predicted by trait responsiveness to verbal suggestion and absorption. These findings demonstrate that context alone can induce psychedelic effects, with implications for its causal role in psychedelic action.