Ego-dissolution and psychedelics: validation of the ego-dissolution inventory (EDI)

This study (n=691) aimed to validate the Ego-Dissolution Inventory (EDI) as well as to investigate the specificity of the relationship between psychedelics and ego-dissolution. The results demonstrate the psychometric structure, internal consistency, and construct validity of the EDI. It was confirmed that ego-dissolution is specific for experiences induced by psychedelic drugs and not by alcohol or cocaine.

Authors

Carhart-Harris, R. L.
Evans, J.
Nour, M. R.

Published

June 14, 2016

Frontiers in Human Neuroscience

individual Study

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Abstract

Aims: The experience of a compromised sense of “self”, termed ego-dissolution, is a key feature of the psychedelic experience. This study aimed to validate the Ego-Dissolution Inventory (EDI), a new 8-item self-report scale designed to measure ego-dissolution. Additionally, we aimed to investigate the specificity of the relationship between psychedelics and ego-dissolution.Method: Sixteen items relating to altered ego-consciousness were included in an internet questionnaire; eight relating to the experience of ego-dissolution (comprising the EDI), and eight relating to the antithetical experience of increased self-assuredness, termed ego-inflation. Items were rated using a visual analog scale. Participants answered the questionnaire for experiences with classical psychedelic drugs, cocaine and/or alcohol. They also answered the seven questions from the Mystical Experiences Questionnaire (MEQ) relating to the experience of unity with one’s surroundings.Results: Six hundred and ninety-one participants completed the questionnaire, providing data for 1828 drug experiences (1043 psychedelics, 377 cocaine, 408 alcohol). Exploratory factor analysis demonstrated that the eight EDI items loaded exclusively onto a single common factor, which was orthogonal to a second factor comprised of the items relating to ego-inflation (rho = −0.110), demonstrating discriminant validity. The EDI correlated strongly with the MEQ-derived measure of unitive experience (rho = 0.735), demonstrating convergent validity. EDI internal consistency was excellent (Cronbach’s alpha 0.93). Three analyses confirmed the specificity of ego-dissolution for experiences occasioned by psychedelic drugs. Firstly, EDI score correlated with drug-dose for psychedelic drugs (rho = 0.371), but not for cocaine (rho = 0.115) or alcohol (rho = −0.055). Secondly, the linear regression line relating the subjective intensity of the experience to ego-dissolution was significantly steeper for psychedelics (unstandardized regression coefficient = 0.701) compared with cocaine (0.135) or alcohol (0.144). Ego-inflation, by contrast, was specifically associated with cocaine experiences. Finally, a binary Support Vector Machine classifier identified experiences occasioned by psychedelic drugs vs. cocaine or alcohol with over 85% accuracy using ratings of ego-dissolution and ego-inflation alone.Conclusion: Our results demonstrate the psychometric structure, internal consistency and construct validity of the EDI. Moreover, we demonstrate the close relationship between ego-dissolution and the psychedelic experience. The EDI will facilitate the study of the neuronal correlates of ego-dissolution, which is relevant for psychedelic-assisted psychotherapy and our understanding of psychosis.

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Research Summary of 'Ego-dissolution and psychedelics: validation of the ego-dissolution inventory (EDI)'

Introduction

Distortions in the subjective sense of self, often referred to as ego-dissolution, are a central feature of the psychedelic experience. Previous work has reported reductions in self-referential awareness with classical 5-HT2A agonists such as psilocybin, LSD and DMT, and related phenomena have been described in other altered states (for example, during ketamine or nitrous oxide use). Existing questionnaires of altered states capture a range of depersonalisation and visionary experiences, but the authors identify a gap: there was no brief, validated, uni-dimensional self-report measure that directly operationalises ego-dissolution as a construct, which limits psychometric, neurobiological and clinical research into this specific aspect of psychedelic states. Nour and colleagues therefore developed the Ego-Dissolution Inventory (EDI), an 8-item self-report scale intended to measure ego-dissolution succinctly. Using an anonymous internet survey, the study aimed to validate the EDI psychometrically (factor structure, internal consistency, convergent and discriminant validity), to test whether ego-dissolution is specifically associated with psychedelic drugs versus cocaine or alcohol, and to explore relationships with dose, subjective intensity and changes in well-being. A secondary hypothesis was that stimulant drugs such as cocaine would be associated with an opposite phenomenon—termed ego-inflation—rather than ego-dissolution.

Methods

The investigators designed 16 novel items about ego-consciousness: eight items intended to capture ego-dissolution and eight intended to capture ego-inflation (elevated self-assuredness). Item selection for the ego-dissolution set was informed by the literature and consensus from six psychedelic neuroscience researchers. Items were interleaved in the online survey to reduce order effects and were rated on 0–100 visual analogue scales (0 = "No, not more than usually"; 100 = "Yes, entirely or completely"). Participants completed a web-based survey (hosted on SurveyGizmo) after providing informed consent. Inclusion criteria were age 18+ and at least one experience with a classical psychedelic (LSD, psilocybin, DMT, ayahuasca or mescaline), cocaine, and/or alcohol. Respondents supplied basic demographics and could report up to four drug experiences: most intense and typical psychedelic experiences, and typical cocaine and alcohol experiences. For each reported experience participants gave a rough dose (LSD-equivalent for psychedelics; categorical ranges for cocaine and alcohol), the subjective intensity of the experience (0–100 VAS), and whether contemplating the experience changed their current well-being on a 7-point scale. For psychedelic experiences, seven items from the Mystical Experiences Questionnaire (MEQ) indexing the unitive/mystical factor were also administered (0–5 scale). A completed form required answers to all 16 ego-consciousness items for at least one experience plus dose, intensity and well-being data. Scores for the 16 items per experience were submitted to exploratory factor analysis (iterated principal axis method with oblique promax rotation); the number of factors was guided by parallel analysis and scree plot inspection. Internal consistency was assessed with Cronbach's alpha (a measure of scale reliability). Convergent validity was tested by correlating the EDI with the MEQ-derived unitive measure; discriminant validity was addressed via factor structure and by comparing the specificity of ego-dissolution to psychedelics versus cocaine and alcohol. The relationship of ego-experiences to dose and subjective intensity was examined using Spearman correlations within drug classes, with Bonferroni correction applied where appropriate. Analysis of covariance (ANCOVA) tested whether the slope of the linear relationship between subjective intensity and ego-experiences differed between drug classes. Finally, a Support Vector Machine (SVM) classifier (linear kernel, 5-fold cross-validation, standard normalisation) was trained on typical experiences using only ego-dissolution and ego-inflation scores to discriminate between psychedelics, cocaine and alcohol. Statistical analyses used SPSS and MATLAB; significance was p < 0.05 (two-tailed) with adjusted thresholds for multiple comparisons where stated. Confidence intervals were obtained by bias-corrected and accelerated bootstrap (1000 samples).

Results

Six hundred and ninety-one participants completed the survey, providing 1828 complete drug-experience records: 1043 psychedelic experiences (584 most intense, 459 typical), 377 cocaine experiences and 408 alcohol experiences. Each participant reported a mean of 2.65 experiences (SD 1.18). Median time since the most intense psychedelic experiences was 1–5 years; typical psychedelic experiences occurred a median of 6–12 months prior to survey completion. Cocaine experiences were typically 1–5 years prior; alcohol experiences were most often within 1–4 weeks. Exploratory factor analysis supported a two-factor structure. The Kaiser-Meyer-Olkin measure was 0.918 and Bartlett's test was highly significant, indicating suitability for factor analysis. Parallel analysis and scree-plot inspection supported extraction of two factors which together explained substantial variance: Factor 1 explained 36.6% and Factor 2 explained 29.5%. All 16 items loaded strongly and exclusively onto one of the two factors, yielding two clear eight-item scales for ego-dissolution and ego-inflation. Communalities ranged from 39% to 82%. Internal consistency was excellent: Cronbach's alpha = 0.93 for the EDI and 0.91 for the ego-inflation scale. Mean item scores correlated almost perfectly with factor scores (rho > 0.99), and the two factors were essentially orthogonal (rho = -0.11), supporting discriminant validity. Convergent validity of the EDI was demonstrated by a strong positive correlation with the MEQ-derived unitive measure for psychedelic experiences (Spearman rho = 0.735, 95% CI [0.704, 0.763], p < 0.001). The unitive measure also correlated with ego-inflation (rho = 0.274) but far less strongly (difference t(1040) = 17.8, p < 0.001). Dose-response analyses showed that for psychedelics reported drug dose correlated positively with ego-dissolution (rho = 0.371, 95% CI [0.317, 0.427], p < 0.001) while the dose–ego-inflation correlation was weak (rho = 0.063, p = 0.043) and did not survive correction for multiple comparisons; the two correlations differed significantly (t(1040) = 8.55, p < 0.001). For cocaine, dose correlated strongly with ego-inflation (rho = 0.385, p < 0.001) but only weakly with ego-dissolution (rho = 0.115, p = 0.026), again a significant difference (t(374) = 4.88, p < 0.001). No significant dose relationships were observed for alcohol. Subjective intensity correlated positively with ego-dissolution for psychedelics (rho = 0.577, 95% CI [0.529, 0.621], p < 0.001) and only weakly with ego-inflation (rho = 0.099). For cocaine and alcohol the opposite pattern held: intensity correlated more strongly with ego-inflation (cocaine rho = 0.545; alcohol rho = 0.502) than with ego-dissolution. ANCOVA confirmed that ego-dissolution was predicted significantly by experience intensity and by drug class; reported regression slopes relating intensity to ego-dissolution were steeper for psychedelics than for cocaine or alcohol. A supervised machine-learning test using an SVM trained on typical experiences with only the two scale scores demonstrated high specificity: classification accuracy was 90.1% for psychedelic versus cocaine (ROC AUC = 0.958) and 85.2% for psychedelic versus alcohol (ROC AUC = 0.927). By contrast, discrimination between cocaine and alcohol was poor (63.4% accuracy, AUC = 0.685). Finally, ego-dissolution correlated positively with self-reported improvements in personal well-being for psychedelic experiences (rho = 0.392, 95% CI [0.342, 0.442], p < 0.001); this relationship was significantly stronger for psychedelics than for cocaine or alcohol. Ego-inflation showed a smaller positive correlation with well-being for psychedelics (rho = 0.198), whereas for cocaine and alcohol ego-inflation tended toward a negative, but nonsignificant, association with well-being after multiple comparison correction.

Discussion

Nour and colleagues interpret their findings as providing initial-phase psychometric validation of the Ego-Dissolution Inventory. The EDI demonstrated a simple single-factor structure for the eight ego-dissolution items, high internal consistency (Cronbach's alpha 0.93), convergent validity with an MEQ-derived unitive measure (rho = 0.735), and discriminant validity from an antithetical ego-inflation factor (orthogonal factor correlation rho = -0.11). The authors argue that ego-dissolution and unitive/mystical experiences are closely related phenomenologically and tend to co-occur during peak psychedelic experiences. The specificity analyses showed that ego-dissolution scales relate to psychedelic dose and subjective intensity more strongly than they do for cocaine or alcohol, while ego-inflation related particularly to cocaine. The SVM classification findings further support the notion that the pattern of ego-experience ratings can distinguish psychedelic experiences from stimulant or alcohol experiences, suggesting utility for phenomenologically driven classification of psychoactive substances. The study team propose that the validated EDI will facilitate more rigorous investigations into the neural correlates of ego-dissolution, for example by combining the scale with neuroimaging measures to test hypotheses about default mode network integrity, network integration and changes in oscillatory power that have previously been associated with ego-related phenomena. The authors acknowledge several limitations. The sample was self-selected and relatively homogeneous—predominantly male, under 30 and with some university education—and many participants were experienced psychedelic users, which may bias responses through prior familiarity with reported psychedelic phenomenology. The online, retrospective design risks recall inaccuracies and cannot verify drug identity or dose; asking participants to estimate psychedelic dose in "LSD-equivalent" units may introduce measurement error that would likely attenuate observed dose–response relationships. The survey did not capture setting variables, which are known to influence psychedelic experiences. Finally, the cross-sectional, retrospective approach limits causal inference. In terms of implications, the investigators suggest the EDI is a concise, reliable tool to quantify ego-dissolution and can be used in future experimental studies, clinical trials of psychedelic-assisted therapy, and neurobiological research. They recommend future work with more heterogeneous samples, prospective or blinded dosing studies to control for recall and setting effects, and comparisons of the EDI with other validated altered-states scales to further establish convergent and discriminant properties. The authors regard the EDI as a step towards better characterising ego-disturbances across both drug-induced states and psychiatric conditions where self-experience is altered.

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INTRODUCTION

Distortions in the subjective experience of one's ''self'', or ''ego'', are central to the psychedelic experience. Specifically, a reduction in the self-referential awareness that defines normal waking consciousness has been reported with all classical psychedelic drugs (5-HT 2A receptor agonists), including psilocybin, lysergic acid diethylamide (LSD;, and dimethyltryptamine (DMT;, as well as with other psychoactive substances such as nitrous oxideand ketamine. The experience of a compromised sense of self occasioned by psychedelic drugs has been variously called ego-death, ego-loss, egodisintegrationand ego-dissolution. This experience has been interpreted from a psychoanalytic perspective as a disruption of ego-boundaries, which results in a blurring of the distinction between selfrepresentation and object-representation, and precludes the synthesis of self-representations into a coherent whole. It is likely that the prior ''psychology'' of the subject and the environmental setting in which they take a psychedelic influences whether an ego-dissolution experience is welcomed and felt as something positive, or feared and fought against. At one extreme, ego-dissolution is closely related to blissful mystical experiences such as can be occasioned by certain spiritual or religious practices; indeed, loss-of-self was identified by William James as being a cardinal feature of the mystical experience. These experiences are characterized by a feeling of unity with one's surroundings, which is explicitly related to disturbed ego-boundaries and thus ego-dissolution. Moreover, the mystical experience is likely to be of therapeutic benefit in psychedelicassisted psychotherapy. At the other extreme, it has been argued that self-disturbances and disturbed ego-boundaries are a core phenomenological feature of psychosis and schizophrenia, although it remains unclear precisely how the self-disturbances specific to schizophrenia relate to the experience of ego-dissolution under psychedelics. Discussions of altered self-experience have been traditionally confined to philosophy or descriptive psychopathology. In recent years, however, there has been increased interest in the neurobiological correlates of the experience of self. Psychedelic drugs may provide a fruitful avenue of research into the neuronal correlates of normal and abnormal self-awareness or ego-consciousness. This research programme, however, is predicated on the existence of a validated self-report measure of the ego-dissolution experience. There currently exist several measures that capture feelings related to alterations in self-experience). Dittrich's APZ (Abnormal Mental States) questionnaire, and its revised versions, OAV and 5D-ASC, have been used extensively to characterize altered states of consciousness occasioned by psychedelic drugs. These questionnaires purport to capture both positive and negative experiences of depersonalization and derealization (''oceanic boundlessness'' and ''dread of ego dissolution'', respectively), as well as additional dimensions of ''visionary restructuralization'' (in APZ, OAV and 5D-ASC), ''auditory alterations'' and ''vigilance reductions'' (both in 5D-ASC only;. Recent psychometric evaluation of the OAV questionnaire, however, reveals a more complex 11-factor structure, including factors relating to changes in cognition, perception and mood, as well as to feelings of unity and disembodiment. At present, however, there are no validated scales that allow an easy, reliable and direct uni-dimensional measurement of egodissolution. This presents a barrier to this promising line of research. The primary aim of the present study was to develop and validate the ''Ego-Dissolution Inventory'' (EDI), a new succinct 8-item self-completed questionnaire designed to operationalize the experience of ego-dissolution so that its construct validity can be tested and developed. In order to do this in an efficient way we chose to utilize online data collection via a large anonymous internet survey. A secondary aim was to investigate the specificity of the relationship between the experience of ego-dissolution and psychedelic drugs, compared with cocaine and alcohol. These two comparator drugs were chosen because of their widespread availability and use in Western societies. Finally, we aimed to test the hypothesis that experiences occasioned by classical stimulant drugs, like cocaine, are in some respects antithetical to the psychedelic experience, promoting ego-inflation rather than egodissolution.

EGO-DISSOLUTION INVENTORY ITEM SELECTION

Sixteen novel statements relating to the experience of ego-consciousness were included in this study. Eight of these were designed to capture the central phenomenon of egodissolution (and the associated feeling of increased union with one's surroundings, known as dissolved ego-boundaries), and particularly how it has been characterized in the context of the psychedelic experience. As well as referring to the existing literature on the psychedelic experience, we also sought the opinion of six scientists working within the field of psychedelic neuroscience when choosing the final eight ego-dissolution items, and sought consensus about the chosen items. The other eight items were designed to reflect the distinct and largely antithetical experience of unusually elevated self-assuredness and confidence (which we refer to as ''ego-inflation''). The items from these two subscales were included in the final survey in an interleaved manner with the intention of minimizing question ''order'' effects, and the potential tendency for subjects to indiscriminately endorse any statement about altered consciousness when reflecting on an experience with a psychoactive substance (particularly if that substance can have profound and variegated psychological effects, as is the case with psychedelics). Items were rated using a visual analog scale format (0-100, with incremental units of one) with zero defined as ''No, not more than usually'', and 100 defined as ''Yes, entirely or completely'', taking inspiration from a previous questionnaire on altered states of consciousness developed byas well as other self-constructed scales used internally by our team. For the exact wording of the 16 ego-consciousness items included in the survey see Table.

SURVEY STRUCTURE

Each subject was asked to provide information on their age, sex and educational background. Subjects also provided information on their lifetime use of psychedelic drugs and cocaine, as well as their weekly alcohol consumption (all possible answer options for educational attainment and drug and alcohol use are presented in Table). After providing these demographic data, subjects were given the opportunity to answer questions on up to four drug experiences: (1) their ''most intense'' psychedelic experience; (2) a ''typical'' psychedelic experience; (3) a ''typical'' cocaine experience; and (4) a ''typical'' alcohol experience. For psychedelic experiences subjects could further specify the drug taken (options were: LSD, psilocybin, mescaline, DMT and ayahuasca). For each experience subjects were asked to provide information on how long ago the experience was (options were: ''Today'', ''Last week'', ''1-4 weeks'' ago, ''1-6 months'' ago, ''6-12 months'' ago, ''1-5 years'' ago, ''6-10 years'' ago, and ''Over 10 years'' ago). They were also asked how ''intense'' the experience was (for psychedelic experiences), or how ''energized/wired'' or ''inebriated/drunk'' they felt (for cocaine and alcohol experiences, respectively) on a visual analog scale from 0 to 100, with 0 = ''Not at all'' and 100 = ''The most intense/energized/inebriated imaginable''. The rationale for enquiring about a typical and most intense experience with psychedelics was to collect a greater range of possible responses with regards to psychedelics, which was our primary drug class of interest. For each experience subjects were also asked to state the dose of the drug taken. For psychedelic drugs, subjects were asked to provide a ''rough/ballpark'' estimate using an LSDequivalent dose; available options ranged from ''No more than half a tab/50 micrograms of LSD'' to ''More than 3 tabs/300 micrograms of LSD'', split into 5 non-overlapping groups. This was done with the aim of providing a standard reference against which any non-LSD classical psychedelic could be compared. For cocaine, the dose options available ranged from: ''less than 1/8 gram'' to ''More than 2 grams'', split into six non-overlapping groups. For alcohol, the dose options ranged from: ''Less than 3 units'' to ''Over 24 units'', split into nine non-overlapping groups. For each drug experience, subjects answered the question ''Do you believe that the experience [induced by the relevant drug] and your contemplation of that experience have led to a change in your current sense of personal well-being or life satisfaction?'' using a 7-point rating scale (+3 = ''increased very much''; +2 = ''increased moderately''; +1 = ''increased slightly''; 0 = ''no change''; -1 = ''decreased slightly''; -2 = ''decreased moderately''; and -3 = ''decreased very much''), taken from the persisting effects questionnaire as per. Subjects then answered the 16 ego-consciousness items (Table) relating to each specific drug experience in question. For experiences occasioned by psychedelic drugs, subjects additionally answered seven questions selected from the Mystical Experiences Questionnaire (MEQ;. The seven questions selected have been shown to load onto a single common factor denoting ''Mystical'' experiences, and all relate to the so-called ''unitive'' experience, which is considered to be a fundamental feature of the mystical experiences. The unitive experience is related to the notion of dissolved ego-boundaries, and it has been hypothesized (although never formally investigated) that the phenomenology of the unitive experience overlaps with that of ego-dissolution. The inclusion of the relevant MEQ questions in this survey allowed us to explicitly test this hypothesis, and provided a means of measuring the convergent validity of the ego-dissolution construct. The specific MEQ questions included, and their relevant MEQ30 identifiers, were as follows: ''Freedom from the limitations of your personal self and feeling a unity or bond with what was felt to be greater than your personal self'' [MEQ30 Q14], ''Experience of oneness in relation to an 'inner world' within'' [MEQ30 Q20], ''Experience of the fusion of your personal self into a larger whole'' [MEQ30 Q26], ''Experience of unity with ultimate reality'' [MEQ30 Q28], ''Feeling that you experienced eternity or infinity'' [MEQ30 Q05], ''Experience of oneness or unity with objects and/or persons perceived in your surroundings'' [MEQ30 Q06] and ''Experience of the insight that 'all is One''' [MEQ30 Q18]. Each item was rated on a 6-point scale, where 0 = ''none, not at all''; 1 = ''so slight cannot decide''; 2 = ''slight''; 3 = ''moderate''; 4 = ''strong (equivalent in degree to any previous strong experience or expectation of this description)''; and 5 = ''extreme (more than ever before in my life and stronger than four)''. This is consistent with the standard procedure for completion of the MEQ.

DISSEMINATION OF THE SURVEY

This study was approved by the local ethics committee. The survey was implemented and hosted by the online service Survey Gizmo, and was estimated to take 38 min to complete. Survey Gizmo has comprehensive privacy policies and security features that maintain the anonymity of responses in line with ethics requirements. Participants were recruited to take the online survey via weblink advertisements posted on Facebook groups, Twitter pages, email newsletters, and online drug forums with a short request (''please participate in our anonymous online questionnaire designed to learn more about experiences with classical psychedelics, cocaine, and alcohol''). Recruitment targeted online communities interested in psychoactive substances and altered states of consciousness (e.g., Psychedelic Society, and Multidisciplinary Association for Psychedelic Studies), as well as websites visited by more diverse populations, (e.g., Reddit, and Mumsnet). The collection of IP addresses and geographical locations of participants was disabled and participants were informed of the anonymity of their responses. After reading a summary of the inclusion criteria and instructions, participants provided informed consent by clicking ''next'' on the first page of the questionnaire. Inclusion criteria for participants were: (1) at least 18 years of age; and (2) had had at least one experience with a classical psychedelic (LSD, psilocybin, DMT, ayahuasca or mescaline), cocaine, and/or alcohol. Data collection occurred over a 4-week period.

FACTOR ANALYSIS AND DEFINITION OF EGO-DISSOLUTION INVENTORY

We defined a completed form as one in which the subject had answered all 16 ego-consciousness items relating to at least one drug experience, and also provided information about the dose of drug taken, the subjective intensity of the experience, and the effect on well-being. Scores for the 16 ego-consciousness items for each complete form were subjected to an exploratory factor analysis using the iterated principle axis factor method and an oblique (promax) rotation, which allowed common factors to be correlated. The appropriate number of factors to be extracted was determined by parallel analysis of principal components using 1000 random drawsand Cattell's scree plot criterion. Based on the factor loadings (from the pattern matrix), the 16 ego-consciousness items could be easily separated into two 8-item scales reflecting ''ego-dissolution'' and ''ego-inflation'' experiences (full details in ''Results'' Section). The mean item scores for both the ego-dissolution and ego-inflation scales were used as a measure of ego-dissolution and ego-inflation for all subsequent analysis.

RELIABILITY AND CONSTRUCT VALIDITY

Internal consistency of the scales was assessed with Cronbach's alpha. Convergent validity of the egodissolution scale was assessed using the correlation with our MEQ-derived measure of unitive experience for psychedelic experiences. Discriminant validity was demonstrated firstly by the ability of an exploratory factor analysis to separate the eight ego-dissolution items from the eight ego-inflation items, and secondly by demonstrating the specificity of ego-dissolution for the psychedelic experience over alcohol or cocaine experiences (see ''Relationship of Ego-Dissolution to Psychedelic Drugs and Persisting Effects'' Section).

RELATIONSHIP OF EGO-DISSOLUTION TO PSYCHEDELIC DRUGS AND PERSISTING EFFECTS

The specificity of the relationship between ego-dissolution and experiences occasioned by classical psychedelics was tested in three ways. Firstly we investigated the correlation between reported drug dose and both ego-dissolution and ego-inflation for each drug class separately (where drug dose was defined as the central value for the selected dose range for each experience). For each drug class the null hypothesis that the dose-ego-dissolution and dose-ego-inflation correlations were equal was tested using a 2-tailed t-test of the differences between dependent correlation coefficients. Secondly, we investigated the relationship between the reported subjective intensity of the experience and egodissolution. Correlations between experience intensity and ego-experiences within a drug class were investigated in an identical manner to the dose-response relationships. As ratings of subjective experience intensity are theoretically comparable across drug classes (unlike drug doses) we were able to test the hypothesis that the linear relationship between subjective intensity and ego-dissolution (or ego-inflation) was different between psychedelic, cocaine and alcohol experiences by testing whether the slope of the linear regression line relating subjective intensity (independent variable) to ego-dissolution or egoinflation (dependent variables) is significantly different between drug classes (using MATLAB's aoctool [Analysis of covariance (ANCOVA)] function). Finally, a Support Vector Machine (SVM) classifier (a common supervised machine learning algorithm) was trained to distinguish between typical experiences with psychedelics, cocaine and alcohol using only the ego-dissolution and egoinflation score for each experience, in three binary one-v-one classification tasks (psychedelic vs. cocaine, psychedelics vs. alcohol, cocaine vs. alcohol). Only ''typical'' psychedelic experiences were included in this analysis to avoid classification problems associated with numerically imbalanced classes. The SVM classifier was implemented in MATLAB 2015b (Mathworks), as part of the Classification Learner application, with the following settings: 5-fold crossvalidation, linear kernel, standard normalization transformation applied to data before entering into SVM classifier. The correlation between ego-dissolution or ego-inflation and reported changes in personal well-being was compared both between and within drug classes using Fisher's r-to-z transform and 2-tailed t-test, respectively. Spearman's rho was used to quantify all bivariate correlations. Statistical significance is defined as p < 0.05 (two-tailed). Multiple statistical comparisons were performed when analyzing the correlation between ego-dissolution or ego-inflation and variables of interest (e.g., drug dose, experience intensity, or change in well-being) separately for the three drug classes. In these instances, we applied Bonferroni correction for multiple comparisons (specifically, six simultaneous comparisons) such that differences are deemed statistically significant for p < 0.008. 95% confidence intervals were calculated using the bias corrected and accelerated bootstrap method (1000 samples). All statistical analysis was performed using SPSS Statistics (IBM, Version 22), and MATLAB (MathWorks, Version 2015b including Statistics and Machine Learning Toolbox).

BASELINE DEMOGRAPHICS OF SURVEY RESPONDERS

Six-hundred and ninety-one subjects completed the online survey. Tablesummarizes the demographic information for these subjects. Each subject answered questions for a mean of 2.65 drug experiences (SD 1.18), providing data for 1828 complete drug experiences for analysis (1043 were with psychedelic drugs: 584 relating to the most intense psychedelic experience and 459 relating to a typical psychedelic experience, occurring a median of 1-5 years and 6-12 months prior to survey completion, respectively. 377 were with cocaine, occurring a median of 1-5 years prior to survey completion. 408 were with alcohol, occurring a median of 1-4 weeks prior to survey completion).

EGO-DISSOLUTION INVENTORY: FACTOR STRUCTURE AND INTERNAL CONSISTENCY

To investigate the factor structure of the 16 ego-consciousness items in a hypothesis-free manner, all questions were submitted to an exploratory factor analysis. The Kaiser-Meyer-Olkin measure of sampling adequacy was 0.918 and Bartlett's test of sphericity was highly significant (χ 2 (120) = 22441.7, p < 0.001) confirming that the data were indeed suitable for factor analysis. Both parallel analysis for principle componentsand inspection of the scree plot using Cattell's criterion) supported a model with two factors or components (parallel analysis observed and 95% confidence interval simulated eigenvalues for the 3rd component were 1.04 and 1.12, respectively). The first component explained 36.6% of the variance in the sample, and the second component explained 29.5% of the variance in the sample. All other components explained <7% of the variance in the sample. The data were therefore subjected to an exploratory factor analysis to extract two common factors. Factor 1 comprised of the eight items relating to the experience of ''ego-dissolution'' whilst Factor 2 comprised of the eight items relating to the experience of ''ego-inflation''. Communality values (the proportion of an item's variance that can be explained by the extracted common factors) ranged from 39% to 82%. Every item loaded strongly and exclusively onto either Factor 1 or Factor 2, demonstrating a simple and easily interpretable factor structure (Table). Guided by the results of the exploratory factor analysis, two 8-item scales were derived, one reflecting the experience of ''egodissolution'', and one reflecting the experience of ''ego-inflation'' (Table). Both scales had excellent internal consistency (Cronbach's alpha = 0.93 and 0.91, respectively;. The mean item scores for both the ego-dissolution and ego-inflation scale were almost perfectly correlated with the factor scores calculated using the regression method from the exploratory factor analysis output (both rho > 0.99, p < 0.001). For ease of interpretability and replication, the mean item scores from the two scales were used as a measure of ego-dissolution and ego-inflation for all subsequent analysis.

CONSTRUCT VALIDITY

For experiences with psychedelic drugs, the score for the MEQ-derived measure of unitive experience correlated strongly with ego-dissolution (rho = 0.735 [95% CI 0.704, 0.763], p < 0.001) providing a clear demonstration of convergent validity. This measure of unitive experience also correlated positively with ego-inflation (rho = 0.274 [0.219, 0.332], p < 0.001) but the strength of this correlation was significantly weaker than that between unitive experience and ego-dissolution (t (1040) = 17.8, p < 0.001). In the exploratory factor analysis, Factor 1 (''ego-dissolution'') and Factor 2 (''ego-inflation'') were essentially orthogonal (rho = -0.11), demonstrating the discriminant validity of ego-dissolution and ego-inflation subscales.

DOSE-RESPONSE RELATIONSHIP

For experiences with psychedelic drugs, there was a significant positive correlation between reported drug dose and egodissolution (rho = 0.371 [0.317, 0.427], p < 0.001), and only a weak correlation between reported drug dose and ego-inflation (rho = 0.063 [0.003, 0.127], p = 0.043), which did not survive correction for multiple comparisons (Figure). The difference between these two correlations was significant (t (1040) = 8.55, p < 0.001). Conversely, for cocaine, there was a significant and strong positive correlation between reported drug dose and ego-inflation (rho = 0.385 [0.390, 0.477], p < 0.001) but only a weak correlation between drug dose and ego-dissolution (rho = 0.115 [0.012, 0.211], p = 0.026), which also did not survive correction for multiple comparisons (Figure). Again, the difference between these two correlations was significant (t (374) = 4.88, p < 0.001). For alcohol there was no dose-response relationship with either ego-dissolution (rho = -0.055 [-0.150, 0.048], p = 0.266) or ego-inflation (rho = -0.054 [-0.148, 0.037], p = 0.328), and no difference between these correlations (t (405) = 0.031, p = 0.488; Figure).

INTENSITY-RESPONSE RELATIONSHIP

For experiences with psychedelic drugs, the subjective intensity of the experience was positively correlated with both egodissolution (rho = 0.577 [0.529, 0.621], p < 0.001) and egoinflation (rho = 0.099 [0.040, 0.159], p = 0.001), although the correlation with ego-dissolution was significantly stronger than that with ego-inflation (t (1040) = 15.1, p < 0.001). The opposite pattern was observed for cocaine and alcohol experiences however, where there was a significantly stronger correlation between the subjective intensity of these drug experiences and ego-inflation (Cocaine: rho = 0.545 [0.464, 0.625], p < 0.001. Alcohol: rho = 0.502 [0.410, 0.582], p < 0.001) than egodissolution (Cocaine: rho = 0.279 [0.180, 0.378], p < 0.001. Alcohol: rho = 0.334 [0.237, 0.421], p < 0.001); (t (374) = 5.33, p < 0.001, and t (405) = 4.03, p < 0.001, for cocaine and alcohol respectively). ANCOVA analysis was used to fit separate regression lines relating subjective intensity (predictor variable) to egodissolution or ego-inflation (dependent variables), for each drug class separately. This analysis confirmed that ego-dissolution experiences were significantly predicted by experience intensity (F (1,1822) = 528.4, MSE = 165132.7, p < 0.001), drug class (F (2,1822) = 636.39, MSE = 198863.7, p < 0.001), and

SUPPORT VECTOR MACHINE CLASSIFIER

As a final demonstration of the specificity of the egodissolution experience for psychedelic drugs, we trained a SVM binary classifier to distinguish between typical psychedelic (n = 459), cocaine (n = 377) and alcohol (n = 408) drug experiences using only the ego-dissolution and egoinflation scores. This classifier achieved an accuracy of 90.1% when distinguishing between psychedelic vs. cocaine experiences (receiver-operator characteristic (ROC) area under the curve (AUC) = 0.958), and 85.2% accuracy when distinguishing between psychedelic and alcohol experiences (ROC AUC = 0.927). By contrast, it performed poorly when distinguishing cocaine from alcohol experiences (63.4% accuracy, ROC AUC = 0.685). Classification at chance level is equivalent to 50% accuracy and ROC AUC = 0.5. Figureillustrates the relationship between ego-dissolution and ego-inflation for experiences occasioned by different drugs.

EGO-DISSOLUTION AND WELL-BEING

As a final exploratory analysis, we sought to investigate the relationship between ego-experiences and the extent to which the experience in question changed subjects' current sense of personal well-being or life satisfaction. For psychedelic drugs, the median response on the 7-point rating scale (with possible answers from -3 to +3) was +2 (+2 = ''Increased moderately'', interquartile range = 2, skewness = -0.769, median time elapsed since experience = 1-5 years), which was significantly There was a trend for a positive correlation between egodissolution score and improvement in well-being across all drug classes, with this effect reaching statistical significance after correction for multiple comparisons only for experiences occasioned by psychedelic drugs (psychedelic: rho = 0.392 [0.342, 0.442], p < 0.001, cocaine: rho = 0.103 [-0.006, 0.204], p = 0.045; alcohol: rho = 0.084 [-0.009, 0.181], p = 0.091). This correlation was significantly stronger for psychedelic drugs compared with either cocaine (Z = 5.15, p < 0.001) or alcohol (Z = 5.63, p < 0.001), but did not differ between cocaine and alcohol drug experiences (Z = 0.267, p = 0.789). Ego-inflation was positively correlated with improvement in well-being for psychedelic drugs (rho = 0.198 [0.135, 0.263], p < 0.001). There was a trend for a negative correlation between ego-inflation and well-being for experiences with cocaine and alcohol however, although these correlations were nonsignificant after correction for multiple comparisons (Cocaine: rho = -0.083.027], p = 0.107. Alcohol: rho = -0.112 [-0.216, -0.014], p = 0.024). Whilst the correlation between ego-inflation and well-being was significantly different for psychedelic drugs compared with both cocaine (Z = 4.71, p < 0.001) and alcohol (Z = 5.53, p < 0.001), it was not significantly different between cocaine and alcohol (Z = 0.408, p = 0.683). For psychedelic experiences, the positive correlation between ego-dissolution and increase in well-being was stronger than between ego-inflation and change in well-being (t (1040) = 5.48, p < 0.001). For both cocaine and alcohol experiences, the negative correlation between ego-inflation and change in wellbeing was stronger than the correlation between ego-dissolution and change in well-being (Cocaine: t (374) = 3.14, p = 0.001. Alcohol: t (405) = 4.13, p < 0.001).

DISCUSSION

The results presented in this study demonstrate the internal consistency, single-factor psychometric structure and construct validity the EDI, a new 8-item self-report questionnaire designed to measure the experience of ego-dissolution. Additionally, our results demonstrate that ego-dissolution positively correlates with drug dose and experience intensity specifically for psychedelic drugs, compared with cocaine or alcohol experiences. This result mirrors the previously demonstrated positive relationship between psilocybin dose and altered states of consciousness, including ''oceanic boundlessness'' and ''dread of ego dissolution'' (as measured by the 5D-ASC questionnaire;and the mystical experience. Indeed, we also found a positive correlation between psychedelic dose and unitive experience (rho = 0.307, p < 0.001). The experience of a coherent and well-circumscribed self is a cardinal feature of adult human waking consciousness. Conversely, the experience of ego-dissolution is unfamiliar to most people, and is related to relatively rare altered states of consciousness, such as the psychedelic experienceand the mystical experience. Despite the relative rarity of the ego-dissolution experience, a fuller understanding of its neurobiological correlates may inform our understanding of the therapeutic mechanism of action of psychedelic drugsand human consciousness more generally. The development and validation of the EDI is an important contribution to this research programme. An understanding of the neurobiological correlates of selfexperience is also of great importance to a number of mental health conditions, where the sense of self is disrupted or compromised. A disrupted sense of self has long been considered to be a core phenomenological feature of acute psychosis. Recently this idea has been extended by, who propose that the core phenomenological alteration in schizophrenia is an ''instability of pre-reflective self-awareness'', which has been termed an ''ipseity-disorder'' or ''self-disorder''. They argue that saturating all subjective experience is a prereflective awareness of self as the unified subject of experience. This notion is closely related to the feeling of inhabiting a living body embedded in the world. As the pre-reflective sense of self is related to a feeling of immersion in a social world, ipseity disturbance may also result in the deficits in social cognition seen in patients. Further research is required to clarify the relationship between the self-disturbances seen in schizophrenia and psychedelic states, as well as the relationship between other features of the psychedelic state and psychosis. Our results represent a necessary step in the demonstration of the construct validity of ego-dissolution. Construct validity can be decomposed into discriminant and convergent validity. Discriminant validity of the EDI was demonstrated by the fact that items relating to ego-dissolution and those relating to ego-inflation loaded onto two orthogonal factors in the exploratory factor analysis. Convergent validity of the EDI was demonstrated by the strong positive correlation between EDI and our (MEQ-based) measure of the unitive experience. This suggests that experiences of ego-dissolution, unity and dissolved ego-boundaries may be conceptually inseparable, occurring together during ''peak'' psychedelic experiences. Consistent with this hypothesis, the item ''I felt at one with the universe'' loaded particularly strongly on the ''ego-dissolution'' factor (0.830), together with items explicitly referring to ''dissolution'' and ''disintegration'' of self or ego (0.883 and 0.897, respectively). Our measure of ego-inflation, in contrast to ego-dissolution, showed a significant dose-response relationship with cocaine, but not psychedelics or alcohol. Although all three drug classes showed a positive correlation between ego-inflation and experience intensity, this relationship was strongest for cocaine and weakest for psychedelic drugs. These results suggest that experiences occasioned by cocaine are in some sense antithetical to the psychedelic experience; with cocaine seeming to promote self-centeredness rather than the selflessness associated with psychedelics. Consistent with this hypothesis, a binary SVM classifier was able to identify experiences occasioned by psychedelic drugs vs. cocaine or alcohol with over 85% accuracy using the ego-dissolution and ego-inflation scores alone. This machine-learning approach may be usefully applied in a number of contexts. For example, it may help to inform debates over whether hybrid compounds such as 3,4methylenedioxymethamphetamine (MDMA) should be classed as ''ego-dissolving'' psychedelic-like agents, ''ego-inflating'' stimulant-like agents, both, or neither. Moreover, used in conjunction with neurobiological measures, such as neuroimaging, these tools may help us to identify key (defining) properties of different psychoactive drugs, as well as nondrug-induced states, in a data-driven manner, and may inform novel hypotheses concerning the endogenous role of 5-HT 2A receptors. This may help us to address questions regarding the similarities and differences of different altered states of consciousness such as dreaming, psychosis and the psychedelic state. More generally, our results suggest that the specific way in which a drug disturbs ego-consciousness may inform a novel phenomenologically-based classification system for psychoactive substances. Subjects in the present study reported that on average their reported experiences with psychedelic drugs had a positive and lasting impact on their well-being, which correlated positively with the degree of ego-dissolution experienced (rho = 0.392). This is consistent with previous work, which has established that mystical (or ''peak'') experiences occasioned by psilocybin correlate positively with increases in ''openness'', well-being, and the meaningfulness/spiritual significance of the experience. Similarly, one influential model of LSD therapy states that the experience of ''ego death and . . . loss of boundaries between the subject and the objective world, with ensuing feelings of unity'' is of great therapeutic benefit. Moreover, lifetime psychedelic use has been associated with reduced odds ratio of psychological distress, suicidality and certain mental health problems in large population samples. Regarding the neurobiology of the psychedelic state, previous work has indicated that psychedelics disrupt the integrity of the default-mode network (DMN), a normally well-integrated network of (mostly cortical) brain regions that display high metabolic demands, ''connector-hub'' status and appear to be involved in high-level functions such as the processing of selfspecific information. Psilocybin and DMT-containing ayahuasca decrease functional connectivity between key DMN hub regions. Psilocybin and LSD also disrupt the functional segregation between usually well-demarcated brain networks, promoting increased global integration, which correlates with ego-dissolution. Disrupted integrity of the DMN and reduced anticorrelation between DMN and task-positive network activity may facilitate a less constrained style of cognition and a weakening of the feeling of a well-circumscribed self. This may be a psychological consequence of a less constrained (more entropic) style of brain activity and a ''collapse'' in the normal hierarchical organization of cortical circuits, which normally functions to finesse perception and cognition by minimizing uncertainty. These previous experimental findings suggest that the integrity of the DMN may be important for normal selfexperience. Relatively few studies have explicitly investigated the neural correlates of ego-dissolution experiences occasioned by psychedelic drugs.found that the experience of ego-disintegration occasioned by psilocybin correlated with decreased alpha power in the posterior cingulate cortex, a DMN hub region, using magnetoencephalography (MEG).by contrast, found that egodissolution correlated with decreased functional connectivity between the anterior parahippocampal cortex and higher-level cortical DMN regions as well as decreased (within-network) integrity of the salience network, and reduced inter-hemispheric communication. A recent study found that the degree of ego-dissolution occasioned by LSD was correlated with global functional connectivity (''Functional Connectivity Density'', as measured by functional magnetic resonance imaging (fMRI)) in bilateral temporo-parietal junction (angular gyrus) and bilateral insular cortex. More generally, this study reported that LSD induced increases in global connectivity in more widespread high-level association cortices, which overlap substantially with the default mode network. A separate analysis of the same fMRI data further revealed that egodissolution showed a strong inverse correlation with DMN network integrity (measured as within-network resting state functional connectivity), and functional connectivity between the parahippocampus and retrosplenial cortex. Moreover, significant relationships were found between ego-dissolution and decreased delta and alpha power (e.g., in posterior cingulate cortex) as measured by MEG, replicating previous findings with psilocybin. One limitation of these studies is that they either used a single-item measure of ego-dissolution, or principle component analysis loadings from an (as yet) unvalidated questionnaire which included items indirectly related to ego-dissolution (e.g., perceptual abnormalities;. Thus, the validated EDI allows for a more rigorous study of the neural correlates of ego-dissolution experienced in a number of altered states of consciousness, including those associated with psychedelic drugs and spiritual practice. The present study has some limitations. Firstly, the population sampled was fairly homogenous, which limits the study's external validity, and thus our ability to extrapolate to a broader demographic. Specifically, most of our subjects were male, under the age of 30, and had at least some university education. Over half the subjects had used classical psychedelic drugs on over 10 occasions. This also raises the possibility that our subjects' responses were biased by their familiarity with reports about paradigmatic features of the psychedelic experience, such as ego-dissolution. Moreover, we did not collect information on the setting in which the psychedelic experiences took place, which is known to influence the quality of the experience. Another important limitation of our study is its retrospective design, which introduces potential inaccuracies in experience recall. We employed an anonymous internet questionnaire design to facilitate the collection of a large data sample of subjects from around the world. Although this approach has its strengths, it is impossible to verify that the experiences attributed to psychedelics were indeed caused by these substances. Finally, we asked subjects to estimate the dose of psychedelic ingested using ''LSD-equivalent'' doses, so as to more easily investigate dose-response relationships across different classical psychedelics. The inaccuracy introduced by this approach, however, is likely to have weakened, rather than strengthened, any observed dose-response relationship between psychedelics and ego-dissolution. Given these limitations, future studies should include a more heterogeneous sampling population, perhaps by intentionally recruiting subjects from different cultural and religious backgrounds, to explore the influence of these factors on ego-dissolution. It would also be of interest to investigate the relationship between responses on the EDI and other validated scales, for example the 5D-ASC. Finally, experimental studies in which a range of psychedelic drug doses are administered to subjects in a blinded manner would be able to assess how subject-specific factors influence the relationship between dose and subjective effects, whilst controlling for recall effects and the effect of setting. In conclusion, the present study offers initial-phase validation of the EDI, and adds to the growing evidence that ego-dissolution is a key phenomenological feature of the psychedelic experience, which may be studied experimentally. The existence of the EDI will facilitate future research into the neural correlates of this experience, which is of relevance for psychedelic-assisted psychotherapy and the phenomenology of certain psychiatric conditions.