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The role of the psychedelic experience in psilocybin treatment for treatment-resistant depression.

Journal of affective disorders
March 1, 2025
Guy M Goodwin et al. (31 authors)
Journal ArticleHuman Study
Study Details

Study Goal

To determine the relationships between psilocybin dose, psychedelic experiences, and therapeutic outcome in treatment-resistant depression.

Results Summary

The intensity of psychedelic effects was dose-related, with depression response correlating with specific aspects of the psychedelic experience. At the 25 mg dose, certain dimensions of the psychedelic experience showed the strongest correlation to improved depression scores at Week 3.

Population

233 participants with treatment-resistant depression

Effective Dosage

Single doses of 25, 10, or 1 mg of COMP360 psilocybin

Duration

Single administration with follow-up at 3 weeks

Interactions

None mentioned

Extracted Claims (5)
InterventionDirectionEndpointPopulationDosageImpactClaim #
COMP360 psilocybin (25 mg dose)
decrease
Week 3 change from Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) score
participants with treatment-resistant depression
Pearson correlation coefficient r = -0.508
correlated with
#1
COMP360 psilocybin (25 mg dose)
decrease
Week 3 change from Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) score
participants with treatment-resistant depression
Pearson correlation coefficient r = -0.516
correlated with
#2
COMP360 psilocybin (25 mg dose)
decrease
Week 3 change from Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) score
participants with treatment-resistant depression
Pearson correlation coefficient r = -0.637
correlated with
#3
COMP360 psilocybin
increase
mean intensity of psychedelic effects
participants with treatment-resistant depression
-
was dose-related
#4
COMP360 psilocybin
neutral
depression response
participants with treatment-resistant depression
-
correlated with
#5
Abstract

OBJECTIVE: To determine the relationships between psilocybin dose, psychedelic experiences, and therapeutic outcome in treatment-resistant depression. METHODS: For treatment-resistant depression, 233 participants received a single dose of 25, 10, or 1 mg of COMP360 psilocybin (a proprietary, pharmaceutical-grade synthesized psilocybin formulation, developed by the sponsor, Compass Pathfinder Ltd.) with psychological support. The resulting psychedelic experience (Five-Dimensional Altered States of Consciousness questionnaire [5D-ASC] and Emotional Breakthrough Inventory [EBI]) were measured. These proximal variables and outcome 3 weeks post-administration (change in Montgomery-Åsberg Depression Rating Scale [MADRS]) were explored using correlation analysis. RESULTS: The mean intensity of psychedelic effects was dose-related, but distributions of scores for different doses overlapped considerably. Depression response correlated with select aspects of the psychedelic experience overall and for individual doses. At the 25 mg dose, 5D-ASC dimensions Oceanic Boundlessness (Pearson correlation coefficient r = -0.508) and Visual Restructuralization (r = -0.516), and EBI (r = -0·637) were the variables with the strongest correlation to the Week 3 change from Baseline in MADRS score. LIMITATIONS: The existence of correlation does not establish causation and exploratory findings require further replication, preferably in larger independent samples. CONCLUSIONS: The intensity of psychedelic experience overlaps widely across doses and mitigates the risk of unblinding to dose. Correlations between psychedelic experience and outcome suggest specificity in psilocybin's mechanism of action. Quality and intensity of psychedelic experience may be a measure of pharmacodynamic effect and reveal an effective dose response phenomenon for single oral doses.

Medical Subject Headings (MeSH)
HumansPsilocybinHallucinogensMaleFemaleAdultDose-Response Relationship, DrugDepressive Disorder, Treatment-ResistantMiddle AgedTreatment OutcomeSurveys and QuestionnairesPsychiatric Status Rating ScalesDepressive Disorder, Major
Study Links
Quality Scores
SafetyNot Assessed
Efficacy75/10
Quality85/10
Citation Metrics
Total Citations3
Citations/Year3.0
Research Impact Scores
APT Score0.25
Weight Score3.07
Normalized Score0.67
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