The Causal Role of Consciousness in Psychedelic Therapy for Treatment-Resistant Depression: Hypothesis and Proposal
ACS Pharmacology & Translational Science July 16, 2025 Tobías Fernández‐borkel, Lucas F. Borkel, Jaime Rojas‐hernández et al. 3 citations
A proposed randomized controlled trial aims to determine whether the subjective psychedelic experience caused by psilocybin is necessary for its antidepressant effects in treatment-resistant depression, or whether neurobiological actions alone suffice. The protocol compares three groups: psilocybin while conscious, psilocybin under propofol-induced general anesthesia (which eliminates subjective experience), and anesthesia with placebo. Clinical assessments and fMRI measures of brain connectivity will be collected. The authors hypothesize that the conscious psilocybin group will show superior improvements in depression and anxiety, and that increased brain fractal complexity and entropy will correlate with therapeutic gains. The results could clarify the causal role of conscious experience in psychedelic therapy.