The Relaxed Beliefs Under pSychedelics (REBUS) model proposes that serotonergic psychedelics decrease the precision weighting of neurobiologically-encoded beliefs. We conducted a preliminary examination of two psychological assumptions of REBUS: (a) psychedelics foster acute relaxation and post-acute revision of confidence in mental-health-relevant beliefs; which (b) facilitate positive therapeutic outcomes and are associated with the entropy of EEG signals. Healthy individuals (N = 11) were administered 1 mg and 25 mg psilocybin 4-weeks apart. Confidence ratings for personally held beliefs were obtained before, during, and 4-weeks post-psilocybin. Acute entropy and subjective experiences were measured, as was well-being (before and 4-weeks post-psilocybin). Confidence in negative self-beliefs decreased following 25 mg psilocybin. Entropy and subjective effects under 25 mg psilocybin correlated with decreases in negative self-belief confidence (acutely and at 4-weeks). Particularly strong evidence was seen for a relationship between decreases in negative self-belief confidence and increases in well-being. We report the first empirical evidence that the relaxation and revision of negative self-belief confidence mediates psilocybin's positive psychological outcomes, and provide tentative evidence for a neuronal mechanism, namely, increased neuronal entropy. Replication within larger and clinical samples is necessary. We also introduce a new measure for examining the robustness of these preliminary findings and the utility of the REBUS model.

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