REBUS model — explaining Carhart-Harris's framework in plain language

Plain language version: Your brain is a prediction machine. It constantly generates predictions about what's happening based on prior beliefs ('priors'), then updates based on sensory input. In depression, the priors get too heavy — the brain over-weights its established beliefs ('I am worthless,' 'nothing will improve') and under-weights evidence that contradicts them. The depressed brain is too confident in its negative model of the world and self. REBUS says psilocybin reduces that over-confidence — temporarily flattening the hierarchy so sensory input and present-moment experience has more weight relative to entrenched prior beliefs.

The therapeutic implication: if your depressive cognitions are being maintained by over-weighted priors, a psilocybin session creates a window where those priors are temporarily loosened — and therapy in that window can install new priors that have a chance of sticking. This is why the combination of psilocybin + therapy outperforms either alone in most trials. The psilocybin opens the door; the therapy walks through it.

The neuroimaging evidence: fMRI shows that the default mode network (DMN) — which mediates self-referential thought and the narrative sense of self — has reduced activity under psilocybin proportional to dose and subjective ego dissolution. Since depression involves hyperactive DMN rumination, this is the brain region you'd most want to interrupt. The REBUS model gives a mechanistic account of why this works rather than just observing that it does.