Longitudinal neural and psychological changes following psilocybin under compassion imagery priming

Psilocybin is a classic psychedelic known to alter subjective experience and induce lasting psychological changes, including increased cognitive flexibility and reduced rigid self-related beliefs. Contextual factors, including preparatory mental states, are thought to play a key role in shaping these effects. Compassion imagery, which engages care-affiliative motivational systems, may represent a promising priming approach in this context. Here, we investigated the neural and psychological effects of psilocybin under compassion imagery priming using self-report questionnaires and functional magnetic resonance imaging (fMRI) in a naturalistic sample of 105 participants. Participants were primed with either compassion imagery or attention to breathing prior to psilocybin intake. We observed sustained increases in absorption over time, particularly in the high-dose compassion imagery condition. Additional within-group increases were found in measures of decentering and self-compassion. Using functional connectivity features, fMRI-based classifiers distinguished between resting state and compassion imagery conditions prior to intake, and between priming conditions following psilocybin, with significant classification performance observed only in the high-dose group. These findings suggest that psilocybin is associated with lasting changes in absorption and may be modulated by contextual priming to shape both psychological outcomes and large-scale brain network dynamics. More generally, our results highlight the potential role of compassion-based practices as preparatory interventions in psychedelic contexts. Future confirmatory studies are needed to further characterize these effects and their underlying mechanisms.