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

This open-label study (n=20) found that the quality of the psychedelic experience (10-25mg psilocybin, measured with the ASC – specifically oceanic boundlessness) predicted therapeutic effect (lower depression scores).


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 have negligible predictive value.

Materials and Methods: Twenty patients with treatment-resistant depression underwent treatment with psilocybin (two separate sessions: 10 and 25 mg psilocybin). The Altered States of Consciousness (ASC) questionnaire was used to assess the quality of experiences in the 25 mg 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. Future therapeutic work with psychedelics should recognize the essential importance of quality of experience in determining treatment efficacy and consider ways of enhancing mystical-type experiences and reducing anxiety.”

Authors: Leor Roseman, David J. Nutt & Robin L. Carhart-Harris


This paper is included in our ‘Top 10 Articles on Psychedelics in the Treatment of Depression

The participants from this study are the same as in Carhart-Harris et al. (2016), an open-label, feasibility study for treatment-resistant depression (TRD). As did the 6-month follow-up in Carhart-Harris et al. (2017).

This study was funded by an MRC clinical development scheme grant (MR/J00460X/1), the Alex Mosley Charitable Trust (G30444), the COMPASS group (I30006), and the Beckley Foundation.

“The so-called “mystical” experience has been a classic problem area for mainstream psychology—if not science more generally.”

“Perhaps the most widely used subjective measure of altered states of consciousness, and particularly the psychedelic state, is the altered states of consciousness questionnaire (ASC) (Dittrich, 1998). We chose this scale over the MEQ as it measures a broader range of subjective phenomena, not just the “mystical-type experience.” Crucially, this enabled us to test the specificity of the relationship between mystical-type experiences (vs. e.g., perceptual changes) and subsequent therapeutic outcomes. “

This study tried to step away from parts of the controversy of the word mystical (which has many more meanings attached to it than implied by the MEQ). And therefore use the ASC, and specifically looked at ‘oceanic boundlessness’ (OBN). The other side of that term/coin is ‘dread of ego dissolution’ (DED).

“Consistent with our prior hypothesis, psilocybin-induced high OBN (sharing features with mystical-type experience) and low DED (similar to anxiety) predicted positive long-term clinical outcomes in a clinical trial of psilocybin for TRD.”

“It remains possible that as yet unmeasured and therefore unaccounted for components of psychedelic therapy play important roles in mediating long-term outcomes. There are several candidate factors in this regard, and the following should not be considered an exhaustive list: emotional insight/breakthrough or catharsis; priming and suggestibility; reliving of trauma/defining life events; insights about the self and relationships; the patients relationship to music heard; his/her success at “letting go”; the quality of therapeutic relationship; and the degree of “closure” attained during post-drug integration work.”

This remains an open question to this day, and something to keep on studying.

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