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Cited by 808Psychedelics and Drug StudiesTreatment of Major DepressionPsychotherapy Techniques and Applications

Quality of acute psychedelic experience predicts therapeutic efficacy of psilocybin for treatment-resistant depression.

Open access
Roseman, Leor, Nutt, David J., Carhart-Harris, Robin L.·2018·Frontiers in Pharmacology
DOI 10.3389/fphar.2017.00974PMC PMC5776504
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Abstract

Introduction: It is a basic principle of the ‘psychedelic’ treatment model that the quality of the acute experience mediates long-term improvements in mental health. In the present paper we sought to test this using data from a clinical trial assessing psilocybin for treatment-resistant depression (TRD). In line with previous reports, we hypothesized that the occurrence and magnitude of Oceanic Boundlessness (OBN) (sharing features with mystical-type experience) and Dread of Ego Dissolution (DED) (similar to anxiety) would predict long-term positive outcomes, whereas sensory perceptual effects would not. Material and Methods: Twenty patients with treatment resistant depression underwent treatment with psilocybin (two separate sessions: 10mg and 25mg psilocybin). The Altered States of Consciousness (ASC) questionnaire was used to assess the quality of experiences in the 25mg psilocybin session. From the ASC, the dimensions OBN and DED were used to measure the mystical-type and challenging experiences, respectively. The Self-Reported Quick Inventory of Depressive Symptoms (QIDS-SR) at 5 weeks served as the endpoint clinical outcome measure, as in later time points some of the subjects had gone on to receive new treatments, thus confounding inferences. In a repeated measure ANOVA, Time was the within-subject factor (independent variable), with QIDS-SR as the within-subject dependent variable in baseline, 1-day, 1-week, 5-weeks. OBN and DED were independent variables. OBN-by-time and DED-by-time interactions were the primary outcomes of interest. Results: For the interaction of OBN and DED with Time (QIDS-SR as dependent variable), the main effect and the effects at each time point compared to baseline were all significant (p = 0.002 and p = 0.003, respectively, for main effects), confirming our main hypothesis. Furthermore, Pearson’s correlation of OBN with QIDS-SR (5 weeks) was specific compared to perceptual dimensions of the ASC (p < 0.05). Discussion: This report further bolsters the view that the quality of the acute psychedelic experience is a key mediator of long-term changes in mental health. More specifically, future therapeutic work with psychedelics may consider investigating ways which enhance mystical-type experience and reduce anxiety, given the growing evidence that this serves the efficacy of the treatment model.

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Crossref · 10.3389/fphar.2017.00974

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  • Many patients describe psychedelic-induced peak or mystical experiences as being among the most meaningful events of their lives, and the intensity of these events correlates with therapeutic responses.

    “Many patients describe psychedelic-induced “peak” or “mystical” experiences as being among the most meaningful events of their lives, and the intensity of these events correlates with therapeutic responses (40, 220–226).”

    From Psychedelics and Other Psychoplastogens for Treating Mental Illness. (2021) · cites this paper as [223]

    The Introduction (page not supplied) says high-dose psychedelic experiences have been rated among the most meaningful of a person's life, but it does not establish that many patients specifically gave that rating. The Discussion (page not supplied) reports that stronger mystical-type features predicted better clinical outcomes in the paper's psilocybin trial. (LLM, conf=0.83)

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  • Psychedelic-induced mystical-type experiences and ego dissolution correlate with long-term positive outcomes.

    “it has been repeatedly found that psychedelic-induced mystical-type experiences and ego dissolution, the latter a phenomenon characterized by the reduction in self-referential awareness, disruption self-world boundaries, and increased feelings of unity with one’s surroundings (55), correlates with long-term (positive) outcomes (23, 52–54, 56–58).”

    From Decreases in State and Trait Anxiety Post-psilocybin: A Naturalistic, Observational Study Among Retreat Attendees (2022) · cites this paper as [54]

    The Discussion reports that psilocybin-induced oceanic boundlessness, which shares features with mystical-type experience, predicted positive long-term clinical outcomes. It describes ego dissolution as a feature of mystical-type experience, but does not establish a separate positive correlation for ego dissolution; greater *dread* of ego dissolution predicted less positive outcomes. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Acute disruption of the default-mode network and mystical-type experiences have been strongly correlated with observed benefits of psychedelics, but the remaining proposed mechanisms still require conclusive testing.

    “Of these proposed mechanisms, the acute disruption of the DMN, as well as mystical-type experiences, have been strongly correlated with observed benefits, but the remainder still require conclusively testing (49, 50).”

    From Examining the Potential Synergistic Effects Between Mindfulness Training and Psychedelic-Assisted Therapy (2021) · cites this paper as [50]

    The Discussion (page unavailable) reports that psilocybin-induced experiences sharing features with mystical-type experiences predicted better clinical outcomes in treatment-resistant depression, and cautions that other factors may contribute. It does not report a correlation between acute default-mode-network disruption and therapeutic benefit or establish that all remaining proposed mechanisms require conclusive testing. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • The anti-depressive and anxiolytic effects of psychedelic-assisted therapy are thought to be mediated by mystical experiences and disrupted cortical connectivity.

    “These anti-depressive and anxiolytic effects are thought to in turn be mediated by enhancements in decentring and cognitive flexibility, in the case of mindfulness intervention (16, 19), vs. mystical experiences and disrupted cortical connectivity in the case of psychedelic-assisted therapy (49, 50).”

    From Examining the Potential Synergistic Effects Between Mindfulness Training and Psychedelic-Assisted Therapy (2021) · cites this paper as [50]

    The Results report that mystical-type experience (measured as oceanic boundlessness) predicted reductions in depression, and the secondary clinical measures include anxiety scores. The Discussion says such experiences may mediate outcomes but cautions that other factors could contribute. It discusses cortical entropy, not disrupted cortical connectivity as a mediator of antidepressant or anxiolytic effects. Page numbers are unavailable in our copy. (LLM, conf=0.87)

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  • Psychedelics are considered safe substances, when administered in a supportive environment by clinicians, with a high potential for therapeutic benefits.

    “Psychedelics are considered safe substances, when administered in a supportive environment by clinicians, with a high potential for therapeutic benefits (50, 160).”

    From Examining the Potential Synergistic Effects Between Mindfulness Training and Psychedelic-Assisted Therapy (2021) · cites this paper as [50]

    The Introduction describes psychedelic dosing in a welcoming environment with support from trained therapists and notes growing evidence of therapeutic value. The Methods and Clinical outcomes sections report supportive psilocybin-assisted sessions and a 47% response rate at five weeks in patients with treatment-resistant depression. The paper does not establish the broader claim that psychedelics are safe substances when administered this way; no safety finding was located in the passages searched. (LLM, conf=0.86)

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Cites

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Research works printed but not linked: 3

  1. Bak P. (1996). ”Complexity and criticality,“ in How Nature Works (New York, NY: Copernicus), 1– 32. 10.1007/978-1-4757-5426-1 · DOI
  2. Freud S. (ed.). (1920). Resistance and suppression, in A General Introduction to Psychoanalysis (New York, NY: Boni & Liveright).
  3. James W. (1902). The Varieties of Religious Experience. Cambridge, MA: Harvard University Press.

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Authors
Roseman, L., Nutt, D. J., & Carhart-Harris, R. L.
Affiliations
Imperial College London (GB)
Corresponding author
Roseman, Leor
ORCID
Venue
Frontiers in Pharmacology
Publisher
Frontiers Media SA
Published
2018-01-17
Volume
8
Pages
974-974
ISSN
1663-9812 (ISSN-L)
DOI
10.3389/fphar.2017.00974
PMC
PMC5776504
OpenAlex
W2792444257
Cited by
808
References
82
Citations by year
2026: 81 · 2025: 129 · 2024: 129 · 2023: 125 · 2022: 115 · 2021: 129 · 2020: 51 · 2019: 25 · 2018: 23 · 2017: 1
FWCI
66.84
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Pharmacology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
  • Spiral (Imperial College London) (submittedVersion, other-oa)
Funders
Medical Research Council (MR/J00460X/1)
Topics
  • Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Social Sciences › Psychology › Clinical Psychology › Psychotherapy Techniques and Applications
Keywords
psilocybin, treatment-resistant depression, ego dissolution, mystical experience, altered states of consciousness, treatment efficacy

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