ArticleACS pharmacology & translational science2025
The Causal Role of Consciousness in Psychedelic Therapy for Treatment-Resistant Depression: Hypothesis and Proposal.
Article in ACS pharmacology & translational science, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
2 citing papers in PubMed.
- Mechanistic insights toward dissociating therapeutic from psychedelic effects: bridging the gap between psychedelic research and mental health care.Translational psychiatry · 2026Review
- Preliminary Findings on Low-Dose 1cp-LSD for Canine Anxiety: Exploring the Role of Owner Neuroticism and Psychopathology.Veterinary sciences · 2025Article
Corrections and comments
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Authors and funding
7 authors.
Funding
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Abstract
The therapeutic potential of psychedelic substances, particularly psilocybin, for treatment-resistant depression (TRD) has garnered considerable attention. However, the necessity of subjective psychedelic experiences for therapeutic efficacy remains unclear, creating a critical gap in the field. To determine whether subjective psychedelic experiences induced by psilocybin are required for its antidepressant effects or whether these effects are mediated solely by neurobiological actions independent of consciousness. We propose a randomized controlled trial with three groups: (P) Psilocybin (25 mg oral dose with guided therapeutic integration), (P+A) Psilocybin under propofol-induced general anesthesia (eliminating subjective experiences), and (X+A) Propofol-induced anesthesia with placebo (with no psilocybin). Clinical assessments of depression and anxiety, combined with fMRI-based brain connectivity analysis (including fractal complexity, brain entropy, and network dynamics), will be conducted at baseline, postintervention, and during follow-ups. The proposed study protocol expects distinct therapeutic outcomes across groups. Superior improvements in depression and anxiety symptoms are anticipated in the conscious psilocybin group (P) compared to both anesthetized groups (P+A) and (X+A). Additionally, increased brain connectivity measures in fractal complexity and entropy are hypothesized to correlate positively with therapeutic improvements, particularly pronounced in the conscious condition. Isolating subjective experiences through anesthesia, aims to determine whether conscious psychedelic experiences play a causal role in therapeutic outcomes. Results have significant implications for clinical protocols, treatment guidelines, and the broader theoretical understanding of consciousness and its relationship to mental health.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.