Scoping Review of Experiential Measures from Psychedelic Research and Clinical Trials

This review (2022) investigates the subjective (experiential) measures that are being used in psychedelic trials and finds good correlations between mystical experiences (MEQ) and oceanic boundlessness and therapeutic/mood outcomes. Similar results (with fewer participants studied) are also found for challenging experiences, psychological insight, and emotional breakthroughs. Alas, not much comment is made about the construct validity of the measures.

Authors

  • De Leo, J.
  • Earleywine, M.
  • Herrmann, Z.

Published

Journal of Psychoactive Drugs
meta Study

Abstract

Subjective responses to psychoactive drugs have served as intriguing windows into consciousness as well as useful predictors. Subjective reactions to psychedelic molecules are particularly interesting given how they covary with subsequent improvements associated with psychedelic-assisted treatments. Although links between subjective reactions and decreases in treatment-resistant clinical depression, end-of-life anxiety, and maladaptive consumption of alcohol and nicotine appear in the empirical literature, the measurement of these subjective responses has proven difficult. Several scales developed over many decades show reasonable internal consistency. Studies suggest that many have a replicable factor structure and other good psychometric properties, but samples are often small and self-selected. We review the psychometric properties of some of the most widely used scales and detail their links to improvement in response to psychedelic-assisted treatments. Generally, assessments of mystical experiences or oceanic boundlessness correlate with improvements. Challenging subjective experiences, psychological insight, and emotional breakthroughs also show considerable promise, though replication would strengthen conclusions. We suggest a collaborative approach where investigators can focus on key responses to ensure that the field will eventually have data from many participants who report their subjective reactions to psychedelic molecules in a therapeutic setting. This may aid in predicting improvement amongst targeted conditions and wellbeing.

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Research Summary of 'Scoping Review of Experiential Measures from Psychedelic Research and Clinical Trials'

Introduction

Psychiatry has seen renewed interest in classical psychedelics for a range of mental health conditions including major depressive disorder, alcohol and tobacco use disorders, obsessive–compulsive disorder, and cancer-related depression and anxiety. These compounds (for example, psilocybin, LSD, DMT, and 5-MeO-DMT) act primarily as serotonin 2A (5-HT2A) receptor agonists and produce dose-dependent alterations in perception, emotion and cognition. Prior work has developed numerous psychometric scales to quantify these subjective experiences, and several studies report associations between specific subjective phenomena (notably mystical-type experiences and oceanic boundlessness) and clinical improvements following psychedelic-assisted interventions. However, scale selection varies widely across investigators and institutions, sample sizes tend to be small or self-selected, and psychometric evidence is scattered, leaving uncertainty about which instruments are most robust and clinically informative. Do and colleagues conducted a scoping review to map the field of experiential measurement in psychedelic research. Their stated aims were to identify the most commonly used scales, describe the attributes of each instrument, and summarise available psychometric properties for measures employed with classical psychedelics (psilocybin, LSD, 5-MeO-DMT, ayahuasca, and DMT). The authors framed this work as preparatory for greater standardisation and collaborative data collection that could improve measurement of subjective mediators in future clinical trials and mechanistic studies.

Methods

The review's literature search and selection were undertaken by named team members: search execution by T.K., selection by Z.H., with discrepancies resolved by S.S. Electronic searches covered PubMed, Embase, Scopus and APA PsycInfo. The search window extended from 1 January 2000 to 30 November 2020, and only English-language studies were considered. Keywords targeted the compounds of interest (ayahuasca, LSD, psilocybin, DMT, 5meoDMT) and commonly used scale names or abbreviations. Inclusion criteria required original research reports that administered multi-item subjective scales in controlled or open-label settings (including naturalistic contexts), involved one of the target compounds, and included human participants. The authors excluded book chapters, conference reports, reviews, online surveys that did not report original multi-item scale data, and purely psychometric studies. The extraction appears to have prioritised multi-item instruments; single-item visual analogue scales and broad mood or intoxication inventories were omitted from the main synthesis. The extracted text does not present a formal risk-of-bias assessment or a detailed data-extraction protocol. The screening process yielded a pool of candidate articles from which included papers were selected, as reported in the Results section.

Results

The authors screened 202 articles (with 84 duplicates removed) and selected 37 publications for detailed review, adding one additional article known to the team, producing a final set of 38 included reports. From these sources the review identified ten multi-item scales in use, with six instruments predominating beyond single-item visual analogue questions. The review excluded several commonly used mood or intoxication inventories (for example, the Addiction Research Center Inventory, State–Trait Anxiety Inventory, Profile of Mood States and Adjective Mood Rating Scale). The Altered States of Consciousness lineage (APZ → OAV → 5D-ASC → 11D-ASC) appears most frequently. The original APZ was developed in 1975 and externally validated after an international study (n = 1,133). Limitations of the APZ’s original binary response format led to the OAV revision, which used visual analogue responses and expanded item coverage. Further revisions produced the 5D-ASC (with added auditory alterations and vigilance reduction dimensions) and later analyses pooled data across 43 experiments (n = 591) to derive an 11-factor structure (11D-ASC) comprising 11 lower-order factors such as Experience of Unity, Spiritual Experience, Blissful State, Insightfulness, Disembodiment and Anxiety. A retrospective sample (n = 177) showed large correlations with the original APZ. The States of Consciousness Questionnaire (SOCQ) and its embedded Mystical Experience Questionnaire (MEQ) were designed to quantify mystical-type experiences, originally as a 100-item instrument extending the MEQ-43 with distractors. Subsequent work produced the briefer MEQ-30 with four factors (mystical, positive mood, transcendence of time and space, ineffability) and acceptable factor structure and internal consistency. The MEQ lineage is used primarily in psilocybin research; a 27-item subset has been employed to compare mystical-type reports in cannabis users, and the MEQ-30 has been validated in French and Finnish samples. The Hallucinogen Rating Scale (HRS) was generated from qualitative interviews with 19 experienced DMT users and administered after low and high DMT doses (reported doses 0.05 mg/kg and 0.4 mg/kg in the formative work). Factor-analytic work produced a large item pool (reported as 126 questions across domains) and an instrument subsequently adapted for broader use. A Spanish translation and psychometric test following ayahuasca experience involved 127 participants; analyses suggested retaining 71 items addressing somesthesia, perception, affect and cognition, whereas volition and intensity subscales did not meet conventional psychometric standards. The HRS has been applied to responses to ketamine, psilocybin, DMT, Salvia divinorum, 2C‑B, MDE, MDMA and ayahuasca. The Hood Mysticism Scale (HMS) originated from theoretical work on mystical experience and was reduced from an initial 108 items to a 32-item instrument. Responses query lifetime experiences and were developed outside the psychedelic context; nevertheless, the HMS is useful given similarities between spontaneous mystical experiences and those occasioned by psychedelics. An initial psychometric sample included 300 college students reporting at least nominal religious affiliation; Cronbach’s alpha was acceptable and factor analyses identified intensity and noetic quality factors. Later work produced a three-factor solution (introvertive mysticism, extrovertive mysticism, and interpretation) that replicated across three samples (n = 1,379; n = 188; n = 185). The Challenging Experience Questionnaire (CEQ) was derived from pooled items (reported pool size N = 64 items) drawn from the HRS, SOCQ and 5D-ASC and developed specifically to capture difficult or adverse facets of hallucinogen experiences. Using exploratory and confirmatory factor analyses, investigators reduced items to a 26-item instrument with a coherent six-factor structure (physiological distress, grief, fear, insanity, isolation, death); a subsequent study evaluated including two paranoia items as a seventh factor and found acceptable fits for both six- and seven-factor models. The CEQ’s factor structure was reported as invariant across gender and prior struggles with anxiety or depression. Factor scores covaried in predictable ways with ratings of difficulty, meaningfulness, spiritual significance and changes in well-being: for example, higher fear related to greater difficulty and lower spiritual significance, whereas increased isolation associated with some increases in well-being but lower meaningfulness and spiritual significance. Across the reviewed scales the authors report generally acceptable internal consistency (Cronbach’s alpha), though they note psychometric weaknesses such as limited sample sizes, items or subscales that fail conventional standards, and the need for replication of factor structures in larger, diverse samples. The review also highlights emerging instruments discussed in the Discussion section, including the Ego Dissolution Inventory (EDI; eight items), the Emotional Breakthrough Inventory (EBI; six items) and the Psychological Insight Questionnaire (PIQ; 23 items with two subscales: Avoidance and Maladaptive Patterns Insights, and Goals and Adaptive Patterns Insights), each intended to capture specific experiential components not fully addressed by older scales.

Discussion

Do and colleagues synthesised their findings to emphasise that five instrument lineages dominate psychedelic research: the APZ/OAV/5D-ASC/11D-ASC family, the SOCQ/MEQ family, the HRS, the HMS and the CEQ. The APZ lineage is appealing because it attempts to characterise the entire altered-state experience via multiple subscales (the 11D-ASC has 42 visual analogue items across 11 subscales), but the trade-offs include respondent burden and uncertain clinical relevance for every derived factor. By contrast, the SOCQ/MEQ and HMS focus on mystical-type phenomena; these targeted measures have gained traction because several trials report correlations between mystical-type scores and clinical improvement, which has clinical implications for selecting agents, doses and therapeutic models. The authors caution that evidence for the ability of psychometric scales to distinguish among psychedelics is mixed. The 11D-ASC has revealed differences (for example, MDMA producing less imagery but more blissful state than psilocybin; ketamine producing more disembodiment), yet other work suggests limits to discrimination at equivalent doses—for instance, the 5D-ASC may not reliably separate LSD from psilocybin, even though some MEQ subscales (ineffability) showed dose-related differences. Situational contributors to subjective intensity also matter: procedures such as PET scanning may amplify reported effects, and the authors highlight the importance of identifying contextual moderators of experiential intensity. Several methodological and practical limitations are emphasised. Many scale responses are positively skewed and kurtotic, so standard parametric analyses may be inappropriate; the authors recommend either developing items that produce finer gradations of effect, removing items insensitive to particular compounds, or adopting robust statistical alternatives. They also note that correlational estimates may be unstable in small samples and cite simulation-based guidance that correlations rarely stabilise for samples smaller than about 250, implying a need for pooled, collaborative datasets. The review further warns against exclusive focus on mystical experience: established mediators of psychotherapeutic and pharmacological outcomes (for example, dysfunctional attitudes, therapeutic alliance, psychological flexibility and behavioural activation) should be linked to subjective psychedelic measures to determine whether experiential variables are mechanistic mediators or epiphenomenal correlates. Regarding instruments that target other experiential domains, the CEQ is highlighted as valuable for capturing challenging experiences, though studies show mixed findings on whether challenging experiences predict outcomes. Newer brief measures—the EBI (emotional breakthrough) and the PIQ (psychological insight)—are promising for measuring potentially predictive, concise constructs, but the authors call for more data and qualitative content to understand what these brief scores represent. Finally, the review acknowledges its own limitations: the search end date of 30 November 2020 may have missed later work, some included articles may not have reported every administered scale in their published outputs, and not all included studies were therapeutic trials despite the review’s clinical orientation.

Conclusion

Do and colleagues conclude that five scale families (APZ lineage, SOCQ/MEQ lineage, HRS, HMS and CEQ) are commonly used in psychedelic research, with reported usage frequencies varying widely (5% to 71%). Psychometric evidence to date shows generally acceptable internal consistency, but comparisons across instruments and robust replication of factor structures are limited. Whether these scales reliably measure mediators of clinical outcome that translate into practical treatment decisions remains unclear. The authors recommend continued assessment using relevant scales, larger collaborative datasets, pre-registration and open data sharing to determine whether specific subjective effects consistently predict better outcomes in psychedelic-assisted treatments.

Study Details

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