Psilocybin and Default Mode Network Suppression: A Review

This review synthesizes fMRI and MEG evidence from 14 studies (2012–2024) examining psilocybin's effect on the default mode network (DMN). Consistent findings show decreased BOLD signal in the medial prefrontal cortex and posterior cingulate cortex, the two major DMN hubs, following moderate-to-high doses (0.2–0.4 mg/kg).

The magnitude of DMN suppression correlates strongly with subjective reports of ego dissolution (r = 0.68, p < 0.001 across pooled data). Participants who reported the most profound mystical-type experiences showed the greatest reduction in DMN integrity, suggesting a mechanistic link between network desegregation and the dissolution of self-referential processing.

Implications for therapeutic application are significant. Conditions characterized by rigid self-referential loops — treatment-resistant depression, OCD, addiction — may benefit from the temporary disruption of these patterns. However, the review cautions that DMN suppression alone is insufficient; the therapeutic context (set, setting, integration) mediates whether the disruption produces lasting benefit or transient disturbance.