Regional specificity of the cingulate cortex thickness association with the intensity of psilocybin experience: a replication study

Individual variability in psilocybin response is a major challenge for psychedelic-assisted therapy, with structural brain features potentially serving as predictive biomarkers. (Lewis et al. Biomedicines 8(2):34 2020) reported that rostral anterior cingulate cortex thickness predicted emotional experiences under psilocybin, suggesting cortical morphometry as a marker of psychedelic responsivity. This study sought to replicate and extend these findings by examining associations between cingulate thickness and psilocybin-induced altered states of consciousness using comprehensive assessment and rigorous statistical control. Twenty-five healthy participants underwent a double-blind, placebo-controlled crossover design with psilocybin (0.26 mg/kg) and placebo. High-resolution T1-weighted magnetic resonance imaging (MRI) measured cortical thickness across cingulate subregions. Subjective effects were assessed with the Altered States of Consciousness (ASC) questionnaire. Analyses applied false discovery rate (FDR) correction for multiple comparisons. The primary Lewis et al. finding—that rostral anterior cingulate cortex thickness predicts emotional psilocybin responses—showed a comparable effect size (β = 0.523 vs. their range 0.324–0.572) that did not achieve statistical significance (p = 0.297), likely reflecting limited statistical power given our smaller sample (N = 25 vs. N = 55). We identified an anterior–posterior gradient in cingulate thickness that significantly predicted psychedelic experience intensity (r = 0.676, FDR p = 0.0004). Findings indicate that spatial organization within the cingulate cortex provides a neuroanatomical marker of variability in psychedelic response. Results highlight the importance of organizational patterns within the cingulate cortex, rather than focal regional measures, when predicting psychedelic effects.